AHF: Gilead’s $1,000 Hepatitis C Pill Target of SF, NYC Protests Feb.12th
Wednesday, Feb 12th drug pricing protests target Gilead over price of Sovaldi, its new Hepatitis C drug: $84,000 for a twelve week supply—or $1,000 per pill!
New York City Protest—12pm to 1pm, Leerink Swann Global Healthcare Conference, Waldorf Astoria Hotel, 301 Park Ave, NY, NY 10022
San Francisco Protest March—12pm to 1pm, March from SF City Hall to the Federal Building
February 12, 2014 08:00 AM Eastern Standard Time
NEW YORK--(BUSINESS WIRE)--Advocates from AIDS Healthcare Foundation (AHF), the nation’s largest HIV/AIDS nonprofit medical provider, is spearheading two protests in New York City and San Francisco on Wednesday February 12th at 12 noon in each city targeting Gilead Sciences over the price of Sovaldi (sofosbuvir), its new Hepatitis C drug. The drug, which was approved by the Food and Drug Administration (FDA) in early December, was immediately priced by Gilead at $84,000 Wholesale Acquisition Cost (WAC) for a twelve-week supply of the drug—or $1,000 per pill.
“Gilead’s $84,000 drug Sovaldi is only one portion of a two drug, twelve-week combination treatment for Hepatitis C, which affects and estimated 3.2 million people in the United States. The two-drug combo pushes treatment to well over $100,000 per patient—a price point that is simply not sustainable”
WHAT:
NEW YORK DRUG PRICING PROTEST/Gilead Sciences’ $1K Hepatitis pill
WHEN:
WEDNESDAY, Feb. 12, 2014
12:00 – 1:00pm EASTERN Time
WHERE:
Leerink Swann Global Healthcare Conf., Waldorf Astoria Hotel, 301 Park Ave, NYC 10022
WHO:
Jessica Reinhart, Senior Grassroots Community Manager, AHF
Michael Camacho, MPH, NYC Regional Director, AHF
And 15-20 drug pricing advocates & protesters with “Gilead-Outrage!” banners, signs and face masks
NY CONTACT:
Jessica Reinhart, Senior Grassroots Community Manager, AHF +1 (323) 203-6146.
WHAT:
SAN FRANCISCO DRUG PRICING PROTEST MARCH/Gilead Sciences’ $1K pill
WHEN:
WEDNESDAY, Feb. 12, 2014
12:00 – 1:00pm PACIFIC Time
WHERE:
Marching FROM:
San Francisco CITY HALL, 1 Dr. Carlton B. Goodlett Place, S.F., CA 94102
Marching TO:
San Francisco FEDERAL BUILDING, 90 7th Street (corner Mission & 7th) S. F., CA 94103
WHO:
Jesse Brooks, Regional Advocacy Consultant
Dale R. Gluth, Bay Area Regional Director, AHF
And 15-20 drug pricing advocates & protesters with “Gilead-Outrage!” banners, signs and face masks
SF CONTACT:
Jesse Brooks, Regional Advocacy Consultant (510) 575-8245.
“Gilead’s $84,000 drug Sovaldi is only one portion of a two drug, twelve-week combination treatment for Hepatitis C, which affects and estimated 3.2 million people in the United States. The two-drug combo pushes treatment to well over $100,000 per patient—a price point that is simply not sustainable,” said Jessica Reinhart, Senior Grassroots Community Manager, for AHF, in anticipation of the New York protest held during the Leerink Swann Global Healthcare Conference at the Waldorf Astoria Wednesday February 12th. “Gilead’s history of predatory pricing on its lifesaving medications—first on its HIV drugs, and now, for this new hepatitis medication—sets the stage for protests like ours as well as for direct action from government officials and drug purchasers for government programs seeking to compel Gilead to cut its outrageous pricing. We also want to let the financial industry know that we are not going to simply stand by and watch this price gouging.”
“In addition to protesting the pricing of Sovaldi, our protests will serve as a reminder of Gilead’s previous bad deeds in its pricing and policies,” said Dale R. Gluth, Bay Area Regional Director for AHF in anticipation of the San Francisco protest march from City Hall to the Federal Building set for Wednesday February 12th. “In late 2012, within days of FDA-approval of Gilead’s four-in-one AIDS treatment combination Stribild, the company immediately priced that treatment at $28,500 per patient, per year, Wholesale Acquisition Cost (WAC)—a whopping 37% more than the price of Gilead’s best-selling three-in-one AIDS treatment, Atripla. For the record, $28,500 is more than most U.S. AIDS patients earn in any given year!”
“For Gilead, we have outrage, pure and simple,” said Michael Weinstein, President of AIDS Healthcare Foundation. “There can be no better example of the unbridled greed of the pharmaceutical industry than Gilead’s latest move: pricing its new hepatitis drug at $28,000 per 28-tablet bottle or $1,000 per pill! Gilead’s predatory pricing of Sovaldi is a direct threat to public heath, and it sets the stage for legislators and advocates to demand that officials who purchase drugs for government programs like Medicaid, Medicare and the AIDS Drug Assistance Programs act decisively to rein in pricing and protect patient access to lifesaving medications.”
Gilead did not even pay to research and develop Sovaldi. In 2011—for $11 billion in cash—it purchased Pharmasset, the company that had already developed the drug. Advocates now believe the pricing of Sovaldi is being driven by Gilead’s desire to recoup its financial investment in Pharmasset, and assumes it can accomplish this by charging Medicaid and other taxpayer-funded programs whatever it wants.
AIDS Healthcare Foundation (AHF), the largest global AIDS organization, currently provides medical care and/or services to more than 282,000 individuals in 32 countries worldwide in the US, Africa, Latin America/Caribbean, the Asia/Pacific Region and Eastern Europe. To learn more about AHF, please visit our website: www.aidshealth.org, find us on Facebook: www.facebook.com/aidshealth and follow us on Twitter: @aidshealthcare
Contacts
NEW YORK
AIDS Healthcare Foundation
Jessica Reinhart
Sr. Grassroots Community Mgr.
Cell: +1-323-203-6146
Jessica.reinhart@aidshealth.org
or
SAN FRANCISCO
AIDS Healthcare Foundation
Jesse Brooks
Regional Advocacy Consultant
Cell +1-510-575-8245
Jesse.brooks@aidshealth.org
pr
LOS ANGELES
AIDS Healthcare Foundation
Ged Kenslea
Senior Director, Communications
+1-323-308-1833 [work] +1-323-791-5526 [cell]
gedk@aidshealth.org
Showing posts with label GS-7977 now Sofosbuvir. Show all posts
Showing posts with label GS-7977 now Sofosbuvir. Show all posts
Wednesday, February 12, 2014
Gilead COO: Analysts' sky-high hep C drug view 'not unreasonable'
Investment Commentary
Gilead COO: Analysts' sky-high hep C drug view 'not unreasonable'
Feb 11 (Reuters) - When Gilead Sciences Inc declined to project 2014 revenue for its high-profile new hepatitis C drug last week, its shares fell nearly 7 percent over the next two days.
Wall Street analysts say investors were likely spooked by the omission, concerned it could signal that sales of the new drug, Sovaldi, might not approach sky-high forecasts.
On Tuesday, Gilead President and Chief Operating Officer John Milligan again declined to predict sales of the medicine that won U.S. marketing approval in December. But he also did not dismiss analysts' record-shattering forecasts that the treatment could rake in $5 billion to $6 billion in its first year on the market.
"It would be unprecedented for a drug to launch at that level, but because of the duration of therapy being short, because of the number of patients who are out there who have the disease, it's not unreasonable math to come to that conclusion," Milligan told Reuters on the sidelines at the Bio CEO & Investor conference in New York.
"We're in early launch phase, just two months in, so it's dangerous to extrapolate from two months. I can see the number that's out there. I don't know if it's too high or too low based on the dynamics," Milligan said.
Along with its fourth-quarter results released last week , Gilead reported $139.4 million in Sovaldi sales after less than one month on the market. The drug promises to increase cure rates with a much shorter duration of treatment and far fewer side effects than previous standard regimens.
"We've seen great enthusiasm from the doctors, and the question is how long will they continue to bring those patients in, what experience will they have as we get through this year?" Milligan said.
He noted that a rival hepatitis C regimen from AbbVie Inc with an equally impressive cure rate could hit the market this year and affect sales. But AbbVie's treatment involves more drugs and many more pills a day, likely giving Gilead a competitive edge.
Gilead this week applied for approval of a combination of Sovaldi and an experimental antiviral drug, ledipasvir, that would be taken as one pill once a day, which could also impact future sales.
In late stage clinical trials, the combination provided cure rates well in excess of 90 percent, in some cases with as little as eight weeks of treatment. It would allow patients to avoid use of older hepatitis drugs that can cause troublesome side effects.
Current standard treatment regimens take 24 to 48 weeks and include injected interferon that causes miserable flu-like symptoms, leading many patients to discontinue or delay treatment, and ribavirin, which can cause anemia and other unpleasant side effects.
It is widely believed that thousands of patients have put off treating the virus in order to wait for new drugs such as Gilead's. By being the first of the expected new wave of oral hepatitis C treatments to market, many analysts believe that Gilead will grab the lion's share of those "warehoused" patients.
"Remember, patients who started in December haven't gotten through their 12 weeks of therapy yet, so (doctors) haven't seen that full experience of seeing patients cured and they really won't understand that until we get into the mid part of this year," Milligan said.
"So I encourage people not to get too far ahead of themselves in thinking about that," he said of the multibillion-dollar first-year Wall Street sales forecasts. "I can understand the enthusiasm because you can get to pretty big numbers in a hurry."
Gilead COO: Analysts' sky-high hep C drug view 'not unreasonable'
Feb 11 (Reuters) - When Gilead Sciences Inc declined to project 2014 revenue for its high-profile new hepatitis C drug last week, its shares fell nearly 7 percent over the next two days.
Wall Street analysts say investors were likely spooked by the omission, concerned it could signal that sales of the new drug, Sovaldi, might not approach sky-high forecasts.
On Tuesday, Gilead President and Chief Operating Officer John Milligan again declined to predict sales of the medicine that won U.S. marketing approval in December. But he also did not dismiss analysts' record-shattering forecasts that the treatment could rake in $5 billion to $6 billion in its first year on the market.
"It would be unprecedented for a drug to launch at that level, but because of the duration of therapy being short, because of the number of patients who are out there who have the disease, it's not unreasonable math to come to that conclusion," Milligan told Reuters on the sidelines at the Bio CEO & Investor conference in New York.
"We're in early launch phase, just two months in, so it's dangerous to extrapolate from two months. I can see the number that's out there. I don't know if it's too high or too low based on the dynamics," Milligan said.
Along with its fourth-quarter results released last week , Gilead reported $139.4 million in Sovaldi sales after less than one month on the market. The drug promises to increase cure rates with a much shorter duration of treatment and far fewer side effects than previous standard regimens.
"We've seen great enthusiasm from the doctors, and the question is how long will they continue to bring those patients in, what experience will they have as we get through this year?" Milligan said.
He noted that a rival hepatitis C regimen from AbbVie Inc with an equally impressive cure rate could hit the market this year and affect sales. But AbbVie's treatment involves more drugs and many more pills a day, likely giving Gilead a competitive edge.
Gilead this week applied for approval of a combination of Sovaldi and an experimental antiviral drug, ledipasvir, that would be taken as one pill once a day, which could also impact future sales.
In late stage clinical trials, the combination provided cure rates well in excess of 90 percent, in some cases with as little as eight weeks of treatment. It would allow patients to avoid use of older hepatitis drugs that can cause troublesome side effects.
Current standard treatment regimens take 24 to 48 weeks and include injected interferon that causes miserable flu-like symptoms, leading many patients to discontinue or delay treatment, and ribavirin, which can cause anemia and other unpleasant side effects.
It is widely believed that thousands of patients have put off treating the virus in order to wait for new drugs such as Gilead's. By being the first of the expected new wave of oral hepatitis C treatments to market, many analysts believe that Gilead will grab the lion's share of those "warehoused" patients.
"Remember, patients who started in December haven't gotten through their 12 weeks of therapy yet, so (doctors) haven't seen that full experience of seeing patients cured and they really won't understand that until we get into the mid part of this year," Milligan said.
"So I encourage people not to get too far ahead of themselves in thinking about that," he said of the multibillion-dollar first-year Wall Street sales forecasts. "I can understand the enthusiasm because you can get to pretty big numbers in a hurry."
Friday, December 6, 2013
Hepatitis C- Gilead's Sovaldi (Sofosbuvir) Is Now FDA Approved
Related:
Gilead said Friday it would price the drug at $84,000 for one 12-week supply. Patients with a less common subtype of the disease may need to take the drug for 24 weeks, raising the cost to $168,000 for one course of treatment. Drugs already on the market run between $25,000 and $50,000 for a course of treatment.
Food and Drug Administration Approves Gilead’s Sovaldi™ (Sofosbuvir) for the Treatment of Chronic Hepatitis C
Download PDF
– Sovaldi Approved for Use in Genotypes 1, 2, 3 or 4 –
– High Cure Rates (SVR12) and Shortened, 12-Week Course of Therapy for Many Patients –
– First Ever Oral Treatment Regimen for Genotypes 2 or 3 –
– First Regimen for Patients Awaiting Liver Transplantation to Prevent HCV Recurrence –
FOSTER CITY, Calif. --(BUSINESS WIRE)--Dec. 6, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA ) has approved Sovaldi™ (sofosbuvir) 400 mg tablets, a once-daily oral nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen.
Sovaldi’s efficacy has been established in subjects with hepatitis C virus (HCV) genotypes 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meetingMilan criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection. Recommended regimens and treatment duration for Sovaldi combination therapy in HCV mono-infected or HCV/HIV-1 co-infected patients follows:
Sovaldi in combination with ribavirin for 24 weeks can be considered for CHC patients with genotype 1 infection who are interferon ineligible. Additionally, Sovaldi should be used in combination with ribavirin for treatment of CHC patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation to prevent post-transplant HCV infection. Treatment regimen, duration and response to Sovaldi are dependent on viral genotype and patient population, and associated baseline factors. Monotherapy is not recommended. Full Prescribing Information will be available on www.Gilead.com.
TheFDA granted Sovaldi Priority Review and Breakthrough Therapy designation, which is granted to investigational medicines that may offer major advances in treatment over existing options.
“I believe that Sovaldi will have a major impact on public health by significantly increasing the number of Americans who are cured of hepatitis C,” saidIra Jacobson , MD, Chief of the Division of Gastroenterology and Hepatology , Weill Cornell Medical College , New York City and a principal investigator in the Sovaldi clinical trials. “In clinical studies, Sovaldi in combination with other agents achieved very high cure rates while shortening the duration of treatment to as little as 12 weeks and reducing or completely eliminating the need for interferon injections, depending on the viral genotype.”
Chronic hepatitis C affects an estimated 4 million people inthe United States , the majority of whom are “baby boomers” – individuals born between 1945 and 1965. The disease is the nation’s leading cause of liver cancer and liver transplantation, and in recent years has surpassed HIV/AIDS as a cause of death. The current standard of care for HCV involves up to 48 weeks of therapy with a pegylated interferon (peg-IFN)/ribavirin (RBV)-containing regimen, which may not suitable for certain types of patients.
“It is our hope that Sovaldi will mark the beginning of a new era in hepatitis C treatment. Gilead is proud to have played a role in bringing about this important therapeutic advance and we would like to extend our thanks to the many patients and physicians who partnered with us on Sovaldi’s clinical studies,” saidJohn C. Martin , PhD, Chairman and Chief Executive Officer, Gilead Sciences .
Sovaldi’s approval is supported primarily by data from four Phase 3 studies, NEUTRINO, FISSION, POSITRON and FUSION, which evaluated 12 or 16 weeks of treatment with Sovaldi combined with either RBV or RBV plus peg-IFN. Three of these studies evaluated Sovaldi plus RBV in genotype 2 or 3 patients who were either treatment-naïve (FISSION), treatment-experienced (FUSION) or peg-IFN intolerant, ineligible or unwilling (POSITRON). NEUTRINO evaluated Sovaldi in combination with Peg-IFN/RBV in treatment naïve patients with genotypes 1, 4, 5 or 6. In these studies, Sovaldi-based therapy was found to be superior to historical controls (NEUTRINO and FUSION) or to placebo (POSITRON), or non-inferior to currently available treatment options (FISSION) based on the proportion of patients who had a sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12). Patients who achieve SVR12 are considered cured of HCV. Trial participants taking Sovaldi-based therapy achieved SVR12 rates of 50-90 percent. For full study details, see the Clinical Studies section of the full Prescribing Information.
During the FDA’s review, data from two additional Phase 3 studies, VALENCE and PHOTON-1, were added to the NDA as a result of the Breakthrough Designation status. In the VALENCE study, patients with genotype 3 HCV infection were treated with Sovaldi and RBV for 24 weeks. Eighty-four percent of patients in this trial achieved SVR12. The PHOTON-1 study evaluated Sovaldi and RBV for 12 weeks in patients with genotype 2 HCV infection co-infected with HIV-1 and for 24 weeks in patients with genotypes 1 or 3 HCV co-infected with HIV-1. Trial participants achieved SVR12 rates of 76-92 percent. In all Phase 3 studies of Sovaldi, no viral resistance to the drug was detected among patients who relapsed following completion of therapy.
To date, nearly 3,000 patients have received at least one dose of Sovaldi in Phase 2 or 3 studies. Sovaldi combination therapy was well tolerated in clinical studies. Adverse events were generally mild and there were few treatment discontinuations due to adverse events. The most common adverse events occurring in at least 20 percent of patients receiving Sovaldi in combination with Peg-IFN/RBV were fatigue, headache, nausea, insomnia and anemia; see below for Important Safety Information regarding contraindications, warnings and precautions, adverse reactions and drug interactions.
OnNovember 22, 2013 , the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion on Gilead’s application for marketing authorization for Sovaldi. The CHMP opinion was adopted following an accelerated review procedure, which is reserved for medicinal products that are expected to be of major public health interest. This assessment does not guarantee marketing authorization by the European Commission . If approved, Sovaldi could be available in the European Union in the first quarter of 2014. Applications for marketing approval of Sovaldi are also pending in Australia , Canada , New Zealand , Switzerland and Turkey .
Dr. Jacobson is a paid consultant to Gilead.
The Wholesaler Acquisition Cost (WAC) of a 28-tablet bottle of Sovaldi inthe United States is $28,000 .
U.S. Patient Assistance Program
Gilead is committed to ensuring that people with hepatitis C can access Sovaldi and has launched Support Path™ (www.MySupportPath.com) to provide assistance to patients who are uninsured, underinsured or who need financial assistance to pay for the medicine. The program consists of an integrated offering of support services for patients and providers, including:
9 a.m. - 8 p.m. EST .
Global Availability
Gilead is committed to helping ensure access to Sovaldi in resource-limited settings. The company is developing a hepatitis C treatment access program, focusing on those countries with the greatest HCV burden. Full program details will be announced in the coming months.
About Sovaldi
Sovaldi is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. Sovaldi is a direct-acting agent, meaning that it interferes directly with the HCV life cycle by suppressing viral replication. Treatment regimen and duration for Sovaldi are dependent on both viral genotype and patient population. Treatment response varies based on baseline host and viral factors. Monotherapy is not recommended for treatment of CHC.
IMPORTANT SAFETY INFORMATION
Contraindications
Sovaldi combination treatment with ribavirin or with peginterferon alfa plus ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant because of the risk for birth defects and fetal death associated with ribavirin. Contraindications to peginterferon alfa and ribavirin also apply to Sovaldi combination treatment. Refer to the prescribing information of peginterferon alfa and ribavirin for a list of their contraindications.
Warnings and Precautions
Most common (≥20%, all grades) adverse reactions for:
In addition to rifampin and St. John’s wort, coadministration of Sovaldi is not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of sofosbuvir, reducing its therapeutic effect.
AboutGilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California , Gilead has operations in North and South America , Europe and Asia Pacific .
Forward-Looking Statement
Gilead's Sofosbuvir Is FDA Approved
FDA NEWS RELEASE
For Immediate Release: Dec. 6, 2013
Media Inquiries: Stephanie Yao, 301-796-0394, stephanie.yao@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
FDA approves Sovaldi for chronic hepatitis C
Drug is third with breakthrough therapy designation to receive FDA approval
The U.S. Food and Drug Administration today approved Sovaldi (sofosbuvir) to treat chronic hepatitis C virus (HCV) infection. Solvadi is the first drug that has demonstrated safety and efficacy to treat certain types of HCV infection without the need for co-administration of interferon.
“Today’s approval represents a significant shift in the treatment paradigm for some patients with chronic hepatitis C,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.
Sovaldi is the second drug approved by the FDA in the past two weeks to treat chronic HCV infection. On November 22, the FDA approved Olysio (simeprevir).
Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. Most people infected with HCV have no symptoms of the disease until liver damage becomes apparent, which may take several years. Some people with chronic HCV infection develop scarring and poor liver function (cirrhosis) over many years, which can lead to complications such as bleeding, jaundice (yellowish eyes or skin), fluid accumulation in the abdomen, infections or liver cancer. According to the Centers for Disease Control and Prevention, about 3.2 million Americans are infected with HCV.
Sovaldi is a nucleotide analog inhibitor that blocks a specific protein needed by the hepatitis C virus to replicate. Sovaldi is to be used as a component of a combination antiviral treatment regimen for chronic HCV infection. There are several different types of HCV infection. Depending on the type of HCV infection a patient has, the treatment regimen could include Sovaldi and ribavirin or Sovaldi, ribavirin and peginterferon-alfa. Ribavirin and peginterferon-alfa are two drugs also used to treat HCV infection.
Sovaldi’s effectiveness was evaluated in six clinical trials consisting of 1,947 participants who had not previously received treatment for their disease (treatment-naive) or had not responded to previous treatment (treatment-experienced), including participants co-infected with HCV and HIV. The trials were designed to measure whether the hepatitis C virus was no longer detected in the blood at least 12 weeks after finishing treatment (sustained virologic response), suggesting a participant’s HCV infection has been cured.
Results from all clinical trials showed a treatment regimen containing Sovaldi was effective in treating multiple types of the hepatitis C virus. Additionally, Sovaldi demonstrated efficacy in participants who could not tolerate or take an interferon-based treatment regimen and in participants with liver cancer awaiting liver transplantation, addressing unmet medical needs in these populations.
The most common side effects reported in clinical study participants treated with Sovaldi and ribavirin were fatigue and headache. In participants treated with Sovaldi, ribavirin and peginterferon-alfa, the most common side effects reported were fatigue, headache, nausea, insomnia and anemia.
Sovaldi is the third drug with breakthrough therapy designation to receive FDA approval. The FDA can designate a drug as a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may demonstrate a substantial improvement over available therapies for patients with serious or life-threatening diseases. Sovaldi was reviewed under the FDA’s priority review program, which provides for an expedited review of drugs that treat serious conditions and, if approved, would provide significant improvement in safety or effectiveness.
Sovaldi is marketed by Gilead, based in Foster City, Calif. Olysio is marketed by Raritan, N.J.-based Janssen Pharmaceuticals.
For more information:
FDA: Approved Drugs: Questions and Answers
FDA: Drug Innovation
FDA: What’s New at FDA in Hepatitis
CDC: Hepatitis C Information for the Public
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Gilead said Friday it would price the drug at $84,000 for one 12-week supply. Patients with a less common subtype of the disease may need to take the drug for 24 weeks, raising the cost to $168,000 for one course of treatment. Drugs already on the market run between $25,000 and $50,000 for a course of treatment.
Food and Drug Administration Approves Gilead’s Sovaldi™ (Sofosbuvir) for the Treatment of Chronic Hepatitis C
Download PDF– Sovaldi Approved for Use in Genotypes 1, 2, 3 or 4 –
– High Cure Rates (SVR12) and Shortened, 12-Week Course of Therapy for Many Patients –
– First Ever Oral Treatment Regimen for Genotypes 2 or 3 –
– First Regimen for Patients Awaiting Liver Transplantation to Prevent HCV Recurrence –
Sovaldi’s efficacy has been established in subjects with hepatitis C virus (HCV) genotypes 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting
Sovaldi Product Photo
Treatment | Duration | |||||||||
| Genotype 1 or 4 |
Sovaldi + peg-interferon alfa
+ ribavirin | 12 weeks | ||||||||
| Genotype 2 | Sovaldi + ribavirin | 12 weeks | ||||||||
| Genotype 3 | Sovaldi + ribavirin | 24 weeks | ||||||||
Sovaldi in combination with ribavirin for 24 weeks can be considered for CHC patients with genotype 1 infection who are interferon ineligible. Additionally, Sovaldi should be used in combination with ribavirin for treatment of CHC patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation to prevent post-transplant HCV infection. Treatment regimen, duration and response to Sovaldi are dependent on viral genotype and patient population, and associated baseline factors. Monotherapy is not recommended. Full Prescribing Information will be available on www.Gilead.com.
The
“I believe that Sovaldi will have a major impact on public health by significantly increasing the number of Americans who are cured of hepatitis C,” said
Chronic hepatitis C affects an estimated 4 million people in
“It is our hope that Sovaldi will mark the beginning of a new era in hepatitis C treatment. Gilead is proud to have played a role in bringing about this important therapeutic advance and we would like to extend our thanks to the many patients and physicians who partnered with us on Sovaldi’s clinical studies,” said
Sovaldi’s approval is supported primarily by data from four Phase 3 studies, NEUTRINO, FISSION, POSITRON and FUSION, which evaluated 12 or 16 weeks of treatment with Sovaldi combined with either RBV or RBV plus peg-IFN. Three of these studies evaluated Sovaldi plus RBV in genotype 2 or 3 patients who were either treatment-naïve (FISSION), treatment-experienced (FUSION) or peg-IFN intolerant, ineligible or unwilling (POSITRON). NEUTRINO evaluated Sovaldi in combination with Peg-IFN/RBV in treatment naïve patients with genotypes 1, 4, 5 or 6. In these studies, Sovaldi-based therapy was found to be superior to historical controls (NEUTRINO and FUSION) or to placebo (POSITRON), or non-inferior to currently available treatment options (FISSION) based on the proportion of patients who had a sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12). Patients who achieve SVR12 are considered cured of HCV. Trial participants taking Sovaldi-based therapy achieved SVR12 rates of 50-90 percent. For full study details, see the Clinical Studies section of the full Prescribing Information.
During the FDA’s review, data from two additional Phase 3 studies, VALENCE and PHOTON-1, were added to the NDA as a result of the Breakthrough Designation status. In the VALENCE study, patients with genotype 3 HCV infection were treated with Sovaldi and RBV for 24 weeks. Eighty-four percent of patients in this trial achieved SVR12. The PHOTON-1 study evaluated Sovaldi and RBV for 12 weeks in patients with genotype 2 HCV infection co-infected with HIV-1 and for 24 weeks in patients with genotypes 1 or 3 HCV co-infected with HIV-1. Trial participants achieved SVR12 rates of 76-92 percent. In all Phase 3 studies of Sovaldi, no viral resistance to the drug was detected among patients who relapsed following completion of therapy.
To date, nearly 3,000 patients have received at least one dose of Sovaldi in Phase 2 or 3 studies. Sovaldi combination therapy was well tolerated in clinical studies. Adverse events were generally mild and there were few treatment discontinuations due to adverse events. The most common adverse events occurring in at least 20 percent of patients receiving Sovaldi in combination with Peg-IFN/RBV were fatigue, headache, nausea, insomnia and anemia; see below for Important Safety Information regarding contraindications, warnings and precautions, adverse reactions and drug interactions.
On
Dr. Jacobson is a paid consultant to Gilead.
The Wholesaler Acquisition Cost (WAC) of a 28-tablet bottle of Sovaldi in
U.S. Patient Assistance Program
Gilead is committed to ensuring that people with hepatitis C can access Sovaldi and has launched Support Path™ (www.MySupportPath.com) to provide assistance to patients who are uninsured, underinsured or who need financial assistance to pay for the medicine. The program consists of an integrated offering of support services for patients and providers, including:
- Access to dedicated case managers to help patients and their providers with insurance-related needs, including identifying alternative coverage options such as federally-insured programs (e.g.,
Medicaid ,Medicare ) and health exchanges. - Education and support, including a 24/7 nursing support service line and the ability to schedule an onsite visit from a clinical educator.
- The Sovaldi Co-pay Coupon Program, which provides co-pay assistance for eligible patients with private insurance who need assistance paying for out-of-pocket medication costs. Most patients will pay no more than
$5 per co-pay. Co-pay assistance can also be applied toward deductibles and co-insurance obligations. - Gilead will provide support to the
Patient Access Network (PAN) Foundation , an independent non-profit organization that provides assistance for eligible federally-insured and privately-insured patients who need help covering out-of-pocket medication costs. - The Support Path Patient Assistance Program will provide Sovaldi at no charge for eligible patients with no other insurance options.
Global Availability
Gilead is committed to helping ensure access to Sovaldi in resource-limited settings. The company is developing a hepatitis C treatment access program, focusing on those countries with the greatest HCV burden. Full program details will be announced in the coming months.
About Sovaldi
Sovaldi is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. Sovaldi is a direct-acting agent, meaning that it interferes directly with the HCV life cycle by suppressing viral replication. Treatment regimen and duration for Sovaldi are dependent on both viral genotype and patient population. Treatment response varies based on baseline host and viral factors. Monotherapy is not recommended for treatment of CHC.
IMPORTANT SAFETY INFORMATION
Contraindications
Sovaldi combination treatment with ribavirin or with peginterferon alfa plus ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant because of the risk for birth defects and fetal death associated with ribavirin. Contraindications to peginterferon alfa and ribavirin also apply to Sovaldi combination treatment. Refer to the prescribing information of peginterferon alfa and ribavirin for a list of their contraindications.
Warnings and Precautions
- Pregnancy: Use with Ribavirin or Peginterferon Alfa/Ribavirin: Ribavirin therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Female patients of childbearing potential and their male partners must use two forms of non-hormonal contraception during treatment and for at least 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. Refer to the prescribing information for ribavirin.
- Use with Potent P-gp Inducers: Rifampin and St. John’s wort should not be used with Sovaldi as they may significantly decrease sofosbuvir plasma concentration, reducing its therapeutic effect.
Most common (≥20%, all grades) adverse reactions for:
- Sovaldi + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia, and anemia
- Sovaldi + ribavirin combination therapy were fatigue, and headache
In addition to rifampin and St. John’s wort, coadministration of Sovaldi is not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of sofosbuvir, reducing its therapeutic effect.
About
Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that physicians and patients may not see advantages of Sovaldi over other therapies and may therefore be reluctant to prescribe the product, and the risk that public payers may be reluctant to approve or provide reimbursement for the product. In addition, pending marketing applications for Sovaldi in the European Union and other territories may not be approved in the currently anticipated timelines or at all, and marketing approval, if granted, may have significant limitations on its use. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2013 , as filed with the U.S. Securities and Exchange Commission . All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
U.S. full prescribing information for Sovaldi is available at www.Gilead.com
Sovaldi and Support Path are trademarks or registered trademarks of Gilead Sciences, Inc.
For more information on Gilead Sciences , please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
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Source: Gilead Sciences, Inc.
Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936 (Investors)
Cara Miller, 650-522-1616 (Media)
- See more at: http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=1882800&highlight=#sthash.fnT6pYSG.dpuf Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936 (Investors)
Cara Miller, 650-522-1616 (Media)
Gilead's Sofosbuvir Is FDA Approved
FDA NEWS RELEASE
For Immediate Release: Dec. 6, 2013
Media Inquiries: Stephanie Yao, 301-796-0394, stephanie.yao@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
FDA approves Sovaldi for chronic hepatitis C
Drug is third with breakthrough therapy designation to receive FDA approval
The U.S. Food and Drug Administration today approved Sovaldi (sofosbuvir) to treat chronic hepatitis C virus (HCV) infection. Solvadi is the first drug that has demonstrated safety and efficacy to treat certain types of HCV infection without the need for co-administration of interferon.
“Today’s approval represents a significant shift in the treatment paradigm for some patients with chronic hepatitis C,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.
Sovaldi is the second drug approved by the FDA in the past two weeks to treat chronic HCV infection. On November 22, the FDA approved Olysio (simeprevir).
Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. Most people infected with HCV have no symptoms of the disease until liver damage becomes apparent, which may take several years. Some people with chronic HCV infection develop scarring and poor liver function (cirrhosis) over many years, which can lead to complications such as bleeding, jaundice (yellowish eyes or skin), fluid accumulation in the abdomen, infections or liver cancer. According to the Centers for Disease Control and Prevention, about 3.2 million Americans are infected with HCV.
Sovaldi is a nucleotide analog inhibitor that blocks a specific protein needed by the hepatitis C virus to replicate. Sovaldi is to be used as a component of a combination antiviral treatment regimen for chronic HCV infection. There are several different types of HCV infection. Depending on the type of HCV infection a patient has, the treatment regimen could include Sovaldi and ribavirin or Sovaldi, ribavirin and peginterferon-alfa. Ribavirin and peginterferon-alfa are two drugs also used to treat HCV infection.
Sovaldi’s effectiveness was evaluated in six clinical trials consisting of 1,947 participants who had not previously received treatment for their disease (treatment-naive) or had not responded to previous treatment (treatment-experienced), including participants co-infected with HCV and HIV. The trials were designed to measure whether the hepatitis C virus was no longer detected in the blood at least 12 weeks after finishing treatment (sustained virologic response), suggesting a participant’s HCV infection has been cured.
Results from all clinical trials showed a treatment regimen containing Sovaldi was effective in treating multiple types of the hepatitis C virus. Additionally, Sovaldi demonstrated efficacy in participants who could not tolerate or take an interferon-based treatment regimen and in participants with liver cancer awaiting liver transplantation, addressing unmet medical needs in these populations.
The most common side effects reported in clinical study participants treated with Sovaldi and ribavirin were fatigue and headache. In participants treated with Sovaldi, ribavirin and peginterferon-alfa, the most common side effects reported were fatigue, headache, nausea, insomnia and anemia.
Sovaldi is the third drug with breakthrough therapy designation to receive FDA approval. The FDA can designate a drug as a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may demonstrate a substantial improvement over available therapies for patients with serious or life-threatening diseases. Sovaldi was reviewed under the FDA’s priority review program, which provides for an expedited review of drugs that treat serious conditions and, if approved, would provide significant improvement in safety or effectiveness.
Sovaldi is marketed by Gilead, based in Foster City, Calif. Olysio is marketed by Raritan, N.J.-based Janssen Pharmaceuticals.
For more information:
FDA: Approved Drugs: Questions and Answers
FDA: Drug Innovation
FDA: What’s New at FDA in Hepatitis
CDC: Hepatitis C Information for the Public
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
What Everybody Ought to Know About Gilead and Johnson's New Hepatitis C Drugs
Investment Commentary
What Everybody Ought to Know About Gilead and Johnson's New Hepatitis C Drugs
By Todd Campbell
December 6, 2013
A new class of oral drugs for curing hepatits C is hitting the markets this winter, displacing injectible predecessors and ushering in treatments that are shorter and in some cases avoid side-affect riddled interferon.
1. They work better, but not for everyone
This new class of drugs is more effective than the prior-generation injectibles, which include Incivek, now fully controlled by Johnson following Vertex's exit, and Victrelis, made by Merck. Both Gilead and Johnson's new drugs are approved for 12-week treatment courses, far shorter than the 24- to 48-week courses for those predecessors. But both Gilead's and Johnson's drugs don't cure everyone.
In studies, Gilead's sofosbuvir, which will likely be approved as a combination therapy alongside ribavirin, cured roughly 89% of patients with genotype 1, the most common genotype in America. Based on Phase 3 results, Johnson's Olysio cures 84% of cases, but stumbles in patients with the Q80K polymorphism, curing just 58%.
"Given the high frequency of the Q80K polymorphism in the U.S. population and its significant impact on rates of SVR12, DAVP is recommending that all GT1a patients be screened for the Q80K polymorphism. Alternative treatment options should be considered for patients found to be infected with this polymorphic variant," according to the FDA's advisory panel committee recommendation.
That should significantly reduce Olysio's appeal, given that nearly 50% of those with hepatitis C, genotype 1 have Q80K.
2. They come with fewer side effects, but still rely on interferon and ribavirin
The target for all of these drugmakers remains a therapy that is free of side-effect laden interferon and ribavirin. If approved on Dec. 8, Gilead's drug will do away with interferon in treating patients with hepatitis genotypes 2 and 3, but interferon will still be dosed alongside ribavirin for the majority of Americans. Meanwhile, Johnson's Olysio still relies on both interferon and ribavirin.
One of the closest to a truly interferon- and ribavirin-free therapy appears to be Bristol. Bristol's drug daclatasvir is being considered for approval in Japan for use in combination with Bristol's asunaprevir for the tough-to-treat genotype 1b population. That population accounts for 70% of Japanese hepatitis cases. and Bristol's interferon- and ribavirin-free, two-drug combination cleared the disease nearly 85% of the time.
3. Fewer pills, easier regimen
It's not just interferon and ribavirin that make it tough for patients to stick to their drug regimen -- it's the dosing, too. The dosing of multiple drugs and injections with varying treatment schedules makes it hard for patients to adhere to protocols. That can cause them to drop out of treatment, fail to clear the disease, or worse, choose to avoid treatment altogether. As a result, drugmakers are focusing on one-pill solutions.
Unfortunately, current treatments from Gilead and Johnson are multi-pill, which is better, but not ideal. However, one pill treatments should be coming soon. In November, Gilead reported data from a Phase 2 trial showing that 95% of patients were cured by a single, once-daily pill combining sofosbuvir and another Gilead drug, ledipasvir.
4. Increasingly expensive treatment
Some doctors will embrace off-label combinations of sofosbuvir with either daclatasvir or Olysio. Those combinations have shown impressive results in Phase 2 -- so impressive that European regulators have given the nod for compassionate use of daclatasvir, despite Bristol not yet filing for EU approval.
Interim data from a Phase 2 trials combining Olysio with sofosbuvir in patients with liver disease who had failed prior treatment are also remarkable. In that study, the combination delivered a 100% cure rate four weeks following a 12-week course of treatment.
While those combinations offer hope for the most critical cases, they pose a big question for patients and insurers. Analysts peg pricing of Olysio at $67,000 for 12 weeks, and estimates for sofosbuvir are running as high as $100,000 for 12 weeks. For comparison, the cost to treat patients with an interferon and ribavirin combination runs roughly $15,000 to $20,000.
5. Hypercompetitive marketplace
Gilead, Johnson, and Bristol are looking over their shoulders at AbbVie and Merck. Both companies have promising late-stage trials ongoing for treating hepatitis C, with AbbVie guiding for a Q2, 2014 filing with the FDA. In a Phase 3 trial, AbbVie's 3 drug, non-interferon, combination cured 95% of patients with genotype 1. And Merck's MK-5172, combined with MK-8742, produced a cure rate between 96% and 100% in a small Phase 2 trial, prompting the FDA to grant the therapy breakthrough status.
That means investors, patients, and doctors have a lot to consider over the coming year as all these contenders vie for a share of a market Express Scripts thinks will quadruple by the end of 2015.
http://www.fool.com/investing/general/2013/12/06/what-everybody-ought-to-know-about-gilead-and-john.aspx
What Everybody Ought to Know About Gilead and Johnson's New Hepatitis C Drugs
By Todd Campbell
December 6, 2013
A new class of oral drugs for curing hepatits C is hitting the markets this winter, displacing injectible predecessors and ushering in treatments that are shorter and in some cases avoid side-affect riddled interferon.
1. They work better, but not for everyone
This new class of drugs is more effective than the prior-generation injectibles, which include Incivek, now fully controlled by Johnson following Vertex's exit, and Victrelis, made by Merck. Both Gilead and Johnson's new drugs are approved for 12-week treatment courses, far shorter than the 24- to 48-week courses for those predecessors. But both Gilead's and Johnson's drugs don't cure everyone.
In studies, Gilead's sofosbuvir, which will likely be approved as a combination therapy alongside ribavirin, cured roughly 89% of patients with genotype 1, the most common genotype in America. Based on Phase 3 results, Johnson's Olysio cures 84% of cases, but stumbles in patients with the Q80K polymorphism, curing just 58%.
"Given the high frequency of the Q80K polymorphism in the U.S. population and its significant impact on rates of SVR12, DAVP is recommending that all GT1a patients be screened for the Q80K polymorphism. Alternative treatment options should be considered for patients found to be infected with this polymorphic variant," according to the FDA's advisory panel committee recommendation.
That should significantly reduce Olysio's appeal, given that nearly 50% of those with hepatitis C, genotype 1 have Q80K.
2. They come with fewer side effects, but still rely on interferon and ribavirin
The target for all of these drugmakers remains a therapy that is free of side-effect laden interferon and ribavirin. If approved on Dec. 8, Gilead's drug will do away with interferon in treating patients with hepatitis genotypes 2 and 3, but interferon will still be dosed alongside ribavirin for the majority of Americans. Meanwhile, Johnson's Olysio still relies on both interferon and ribavirin.
One of the closest to a truly interferon- and ribavirin-free therapy appears to be Bristol. Bristol's drug daclatasvir is being considered for approval in Japan for use in combination with Bristol's asunaprevir for the tough-to-treat genotype 1b population. That population accounts for 70% of Japanese hepatitis cases. and Bristol's interferon- and ribavirin-free, two-drug combination cleared the disease nearly 85% of the time.
3. Fewer pills, easier regimen
It's not just interferon and ribavirin that make it tough for patients to stick to their drug regimen -- it's the dosing, too. The dosing of multiple drugs and injections with varying treatment schedules makes it hard for patients to adhere to protocols. That can cause them to drop out of treatment, fail to clear the disease, or worse, choose to avoid treatment altogether. As a result, drugmakers are focusing on one-pill solutions.
Unfortunately, current treatments from Gilead and Johnson are multi-pill, which is better, but not ideal. However, one pill treatments should be coming soon. In November, Gilead reported data from a Phase 2 trial showing that 95% of patients were cured by a single, once-daily pill combining sofosbuvir and another Gilead drug, ledipasvir.
4. Increasingly expensive treatment
Some doctors will embrace off-label combinations of sofosbuvir with either daclatasvir or Olysio. Those combinations have shown impressive results in Phase 2 -- so impressive that European regulators have given the nod for compassionate use of daclatasvir, despite Bristol not yet filing for EU approval.
Interim data from a Phase 2 trials combining Olysio with sofosbuvir in patients with liver disease who had failed prior treatment are also remarkable. In that study, the combination delivered a 100% cure rate four weeks following a 12-week course of treatment.
While those combinations offer hope for the most critical cases, they pose a big question for patients and insurers. Analysts peg pricing of Olysio at $67,000 for 12 weeks, and estimates for sofosbuvir are running as high as $100,000 for 12 weeks. For comparison, the cost to treat patients with an interferon and ribavirin combination runs roughly $15,000 to $20,000.
5. Hypercompetitive marketplace
Gilead, Johnson, and Bristol are looking over their shoulders at AbbVie and Merck. Both companies have promising late-stage trials ongoing for treating hepatitis C, with AbbVie guiding for a Q2, 2014 filing with the FDA. In a Phase 3 trial, AbbVie's 3 drug, non-interferon, combination cured 95% of patients with genotype 1. And Merck's MK-5172, combined with MK-8742, produced a cure rate between 96% and 100% in a small Phase 2 trial, prompting the FDA to grant the therapy breakthrough status.
That means investors, patients, and doctors have a lot to consider over the coming year as all these contenders vie for a share of a market Express Scripts thinks will quadruple by the end of 2015.
http://www.fool.com/investing/general/2013/12/06/what-everybody-ought-to-know-about-gilead-and-john.aspx
Tuesday, December 3, 2013
Sofosbuvir for Hepatitis C: Simpler, Shorter, Safer?
Medscape Gastroenterology
Sofosbuvir for Hepatitis C: Simpler, Shorter, Safer?
William F. Balistreri, MD
Dec 3 2013
Aiming for the Ideal Strategy
In 2011, the American Association for the Study of Liver Diseases (AASLD) issued an updated version of its practice guidelines for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection.[1] The current standard-of-care regimens include a protease inhibitor -- telaprevir or boceprevir -- in combination with pegylated interferon (PEG-IFN) and ribavirin. Protease inhibitor-based strategies for patients with genotype 1 HCV have led to high rates of sustained virologic response (SVR); however, there are several recurring concerns.
The disadvantages of IFN treatment are well known. Moreover, this strategy presents a complex and prolonged therapeutic course (24-48 weeks), low tolerability, a low barrier to resistance, and reduced efficacy in prior null responders or cirrhotic patients. These regimens are not an option for many patients because of contraindications or intolerability to IFN.[2-7]
To address these concerns, there has been a massive effort to create the ideal agent or strategy for use in updated therapeutic efforts. The pace of discovery has been unprecedented, and several agents are in the later phases of development. The approach has been to discover drugs that directly target various aspects of the HCV life cycle -- hopefully leading to combinations of agents that will more effectively treat patients, while minimizing intolerable side effects or adverse events
Sofosbuvir Enters the Fray
A recent article discussed simeprevir, an HCV NS3/4A protease inhibitor. [Editor's note: The US Food and Drug Administration (FDA) approved simeprevir (Olysio™) on November 22, 2013.]
The latest drug to emerge from this effort is sofosbuvir. In late October, an FDA advisory panel recommended the approval of sofosbuvir for the treatment of 2 groups of patients with chronic HCV: previously untreated adults with genotypes 1 and 4 infections (in combination with PEG-IFN and ribavirin) and adults with genotype 2 and 3 infections (in combination with ribavirin alone), which would allow an all-oral, IFN-free treatment for these 2 genotypes.
Sofosbuvir, an orally administered nucleotide analogue inhibitor of the HCV NS5B polymerase, exerts potent antiviral activity against HCV genotypes 1 through 6. This drug is meant to be taken once daily at a dose of 400 mg. Sofosbuvir has been extensively studied in various patient populations in combination with PEG-IFN/ribavirin, as well as with other direct-acting antiviral agents in treatment-naive patients with genotype 1 HCV infection.[8-12]
The FDA advisory committee reviewed primary efficacy and safety data from a series of clinical trials. The data supported the possibility of effectively treating HCV infection with a brief, well-tolerated, all-oral, once-daily regimen that has no known safety issues and no resistance development. Phase 3 trials of sofosbuvir in treatment-naive patients with hepatitis C virus genotypes 1 through 6 demonstrated that patients with genotype 1 infection have excellent treatment response that is superior overall to published response rates for combination therapy and currently available triple therapies. For patients with genotypes 2 and 3, efficacy was similar between an IFN-free sofosbuvir regimen and a standard PEG-IFN/ribavirin regimen.
Evidence for Sofosbuvir
Numerous studies have emerged; a brief overview of a few representative studies of sofosbuvir in combination with other direct-acting antiviral agents is offered here:
• Sofosbuvir was combined with simeprevir with and without ribavirin; SVR rates of 93%-96% were reported.[11]
• Sofosbuvir plus the NS5A inhibitor daclatasvir led to SVR at 12 weeks (SVR12) rates of 86%-100%.[13]
• Ledipasvir is a novel HCV NS5A inhibitor that has shown potent antiviral activity against genotypes 1a and 1b HCV infection.[14,15] It is active against HCV with the S282T mutation, the only variant known to reduce susceptibility to sofosbuvir.[16] All treatment-naive patients and prior null responders (noncirrhotic) who received 12 weeks of sofosbuvir and ledipasvir plus ribavirin achieved high SVR12 rates (95%-100%). Patients treated for 12 weeks had a similar response to patients who received 8 weeks of therapy, suggesting that this shorter treatment strategy might be sufficient for noncirrhotic patients who have not previously been treated for HCV.
In all of these studies, sofosbuvir was well tolerated, with a low incidence of adverse events. In conjunction with the suggested brief duration of this regimen, this indicates that drug combinations should improve treatment adherence compared with IFN-based treatment. Traditional predictors of response, such as IL28B genotype and baseline viral load, do not seem to affect response rates. Other large multicenter trials are under way, designed to address the optimal treatment combination and duration, the need for ribavirin, and the efficacy in patients with compensated cirrhosis in both treatment-naive and previously treated patients.
Data on the Drug
Presentations offered at the AASLD's Liver Meeting 2013 abetted the data submitted to the FDA. Several studies reported pan-genotypic efficacy and safety of sofosbuvir, as well as other potential uses for this agent in various drug combinations and in various populations, including the following:
• In a phase 3 trial, 12 weeks of sofosbuvir plus ribavirin demonstrated high SVR rates in a predominantly treatment-experienced patient population with genotypes 2 and 3 HCV infection, with higher response rates in patients infected with genotype 2 than in those infected with genotype 3 HCV.[17]
• In a phase 2, randomized, open-label study, the combination of sofosbuvir plus simeprevir plus ribavirin for 12 or 24 weeks in patients with HCV genotype 1 infection resulted in high SVRs. This study included null responders and patients with cirrhosis.[18]
• Sofosbuvir plus ledipasvir given in a fixed combination elicited a rapid decline in HCV RNA levels in all patient populations, with no viral breakthrough. In treatment-naive patients with genotype 1 infection and without cirrhosis, a reduction in duration of therapy from 12 to 6 weeks increased the rate of relapse.[19] In genotype 1-infected patients who were prior null responders and had cirrhosis, the addition of ribavirin to sofosbuvir and ledipasvir reduced the rate of relapse.
• Treatment-naive patients with HCV genotype 2 and 3 who were coinfected with HIV achieved high SVR12 rates with an IFN-free, oral regimen of sofosbuvir plus ribavirin.[20] The SVR12 rates were 76% among patients with HCV genotype 1, 88% among those with genotype 2, and 67% among those with genotype 3; these are similar to the rates observed for patients infected with HCV only. These preliminary data suggest that sofosbuvir plus ribavirin treatment was well tolerated and safe, even with the coadministration of multiple antiretroviral drugs.
A Markov model, developed to evaluate the long-term outcomes of sofosbuvir-based therapy for HCV infection, indicated that regimens incorporating this agent are highly effective in preventing progression to advanced liver disease.[21]
New Opportunities Bring New Challenges
Recurrence of HCV infection is the most common cause of graft loss and mortality in HCV-infected liver transplant recipients. IFN-based post-transplantation antiviral regimens, including those using protease inhibitors, are poorly tolerated and achieve SVRs that are lower than those in nontransplant patients.
Administration of sofosbuvir plus ribavirin after liver transplantation in the setting of established HCV recurrence was well tolerated, and approximately 80% of patients achieved an early SVR at 4 weeks. There were no episodes of rejection or drug interaction, and there was no apparent effect of sofosbuvir on serum levels of immunosuppressive medications, offering the potential for an all-oral therapy for treatment of HCV infection after liver transplantation.[22] Sofosbuvir and ribavirin may, in fact, be used in the pretransplant phase to prevent recurrence of HCV infection after transplantation.[23]
In summary, 2 novel direct-acting antiviral agents -- sofosbuvir and simeprevir -- target various components of the HCV genome. Advantages of these drugs include a high barrier to viral resistance, a shorter duration of treatment, once-daily dosing, absence of food restrictions, few clinically significant drug interactions, and similar efficacy in all genotypes. This will offer clinicians new options as well as new challenges. A recent review addressed some of these anticipated issues, such as the off-label use of HCV medications and the roles of the FDA, consumer pressure, medical society guidelines, and third-party payers.[24]
The availability of these agents will provide unprecedented opportunities for off-label use of these therapies in many patients, including those with decompensated cirrhosis or chronic kidney disease, pediatric populations, and those with HIV coinfection. Because many of these populations represent relatively small numbers of patients with HCV, it may be difficult to accumulate the requisite data and possibly cost-prohibitive for manufacturers to apply for FDA approval.
The bottom line is that simpler, shorter, and safer strategies for treatment of patients infected with HCV are at hand.
http://www.medscape.com/viewarticle/815115_4
Sofosbuvir for Hepatitis C: Simpler, Shorter, Safer?
William F. Balistreri, MD
Dec 3 2013
Aiming for the Ideal Strategy
In 2011, the American Association for the Study of Liver Diseases (AASLD) issued an updated version of its practice guidelines for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection.[1] The current standard-of-care regimens include a protease inhibitor -- telaprevir or boceprevir -- in combination with pegylated interferon (PEG-IFN) and ribavirin. Protease inhibitor-based strategies for patients with genotype 1 HCV have led to high rates of sustained virologic response (SVR); however, there are several recurring concerns.
The disadvantages of IFN treatment are well known. Moreover, this strategy presents a complex and prolonged therapeutic course (24-48 weeks), low tolerability, a low barrier to resistance, and reduced efficacy in prior null responders or cirrhotic patients. These regimens are not an option for many patients because of contraindications or intolerability to IFN.[2-7]
To address these concerns, there has been a massive effort to create the ideal agent or strategy for use in updated therapeutic efforts. The pace of discovery has been unprecedented, and several agents are in the later phases of development. The approach has been to discover drugs that directly target various aspects of the HCV life cycle -- hopefully leading to combinations of agents that will more effectively treat patients, while minimizing intolerable side effects or adverse events
Sofosbuvir Enters the Fray
A recent article discussed simeprevir, an HCV NS3/4A protease inhibitor. [Editor's note: The US Food and Drug Administration (FDA) approved simeprevir (Olysio™) on November 22, 2013.]
The latest drug to emerge from this effort is sofosbuvir. In late October, an FDA advisory panel recommended the approval of sofosbuvir for the treatment of 2 groups of patients with chronic HCV: previously untreated adults with genotypes 1 and 4 infections (in combination with PEG-IFN and ribavirin) and adults with genotype 2 and 3 infections (in combination with ribavirin alone), which would allow an all-oral, IFN-free treatment for these 2 genotypes.
Sofosbuvir, an orally administered nucleotide analogue inhibitor of the HCV NS5B polymerase, exerts potent antiviral activity against HCV genotypes 1 through 6. This drug is meant to be taken once daily at a dose of 400 mg. Sofosbuvir has been extensively studied in various patient populations in combination with PEG-IFN/ribavirin, as well as with other direct-acting antiviral agents in treatment-naive patients with genotype 1 HCV infection.[8-12]
The FDA advisory committee reviewed primary efficacy and safety data from a series of clinical trials. The data supported the possibility of effectively treating HCV infection with a brief, well-tolerated, all-oral, once-daily regimen that has no known safety issues and no resistance development. Phase 3 trials of sofosbuvir in treatment-naive patients with hepatitis C virus genotypes 1 through 6 demonstrated that patients with genotype 1 infection have excellent treatment response that is superior overall to published response rates for combination therapy and currently available triple therapies. For patients with genotypes 2 and 3, efficacy was similar between an IFN-free sofosbuvir regimen and a standard PEG-IFN/ribavirin regimen.
Evidence for Sofosbuvir
Numerous studies have emerged; a brief overview of a few representative studies of sofosbuvir in combination with other direct-acting antiviral agents is offered here:
• Sofosbuvir was combined with simeprevir with and without ribavirin; SVR rates of 93%-96% were reported.[11]
• Sofosbuvir plus the NS5A inhibitor daclatasvir led to SVR at 12 weeks (SVR12) rates of 86%-100%.[13]
• Ledipasvir is a novel HCV NS5A inhibitor that has shown potent antiviral activity against genotypes 1a and 1b HCV infection.[14,15] It is active against HCV with the S282T mutation, the only variant known to reduce susceptibility to sofosbuvir.[16] All treatment-naive patients and prior null responders (noncirrhotic) who received 12 weeks of sofosbuvir and ledipasvir plus ribavirin achieved high SVR12 rates (95%-100%). Patients treated for 12 weeks had a similar response to patients who received 8 weeks of therapy, suggesting that this shorter treatment strategy might be sufficient for noncirrhotic patients who have not previously been treated for HCV.
In all of these studies, sofosbuvir was well tolerated, with a low incidence of adverse events. In conjunction with the suggested brief duration of this regimen, this indicates that drug combinations should improve treatment adherence compared with IFN-based treatment. Traditional predictors of response, such as IL28B genotype and baseline viral load, do not seem to affect response rates. Other large multicenter trials are under way, designed to address the optimal treatment combination and duration, the need for ribavirin, and the efficacy in patients with compensated cirrhosis in both treatment-naive and previously treated patients.
Data on the Drug
Presentations offered at the AASLD's Liver Meeting 2013 abetted the data submitted to the FDA. Several studies reported pan-genotypic efficacy and safety of sofosbuvir, as well as other potential uses for this agent in various drug combinations and in various populations, including the following:
• In a phase 3 trial, 12 weeks of sofosbuvir plus ribavirin demonstrated high SVR rates in a predominantly treatment-experienced patient population with genotypes 2 and 3 HCV infection, with higher response rates in patients infected with genotype 2 than in those infected with genotype 3 HCV.[17]
• In a phase 2, randomized, open-label study, the combination of sofosbuvir plus simeprevir plus ribavirin for 12 or 24 weeks in patients with HCV genotype 1 infection resulted in high SVRs. This study included null responders and patients with cirrhosis.[18]
• Sofosbuvir plus ledipasvir given in a fixed combination elicited a rapid decline in HCV RNA levels in all patient populations, with no viral breakthrough. In treatment-naive patients with genotype 1 infection and without cirrhosis, a reduction in duration of therapy from 12 to 6 weeks increased the rate of relapse.[19] In genotype 1-infected patients who were prior null responders and had cirrhosis, the addition of ribavirin to sofosbuvir and ledipasvir reduced the rate of relapse.
• Treatment-naive patients with HCV genotype 2 and 3 who were coinfected with HIV achieved high SVR12 rates with an IFN-free, oral regimen of sofosbuvir plus ribavirin.[20] The SVR12 rates were 76% among patients with HCV genotype 1, 88% among those with genotype 2, and 67% among those with genotype 3; these are similar to the rates observed for patients infected with HCV only. These preliminary data suggest that sofosbuvir plus ribavirin treatment was well tolerated and safe, even with the coadministration of multiple antiretroviral drugs.
A Markov model, developed to evaluate the long-term outcomes of sofosbuvir-based therapy for HCV infection, indicated that regimens incorporating this agent are highly effective in preventing progression to advanced liver disease.[21]
New Opportunities Bring New Challenges
Recurrence of HCV infection is the most common cause of graft loss and mortality in HCV-infected liver transplant recipients. IFN-based post-transplantation antiviral regimens, including those using protease inhibitors, are poorly tolerated and achieve SVRs that are lower than those in nontransplant patients.
Administration of sofosbuvir plus ribavirin after liver transplantation in the setting of established HCV recurrence was well tolerated, and approximately 80% of patients achieved an early SVR at 4 weeks. There were no episodes of rejection or drug interaction, and there was no apparent effect of sofosbuvir on serum levels of immunosuppressive medications, offering the potential for an all-oral therapy for treatment of HCV infection after liver transplantation.[22] Sofosbuvir and ribavirin may, in fact, be used in the pretransplant phase to prevent recurrence of HCV infection after transplantation.[23]
In summary, 2 novel direct-acting antiviral agents -- sofosbuvir and simeprevir -- target various components of the HCV genome. Advantages of these drugs include a high barrier to viral resistance, a shorter duration of treatment, once-daily dosing, absence of food restrictions, few clinically significant drug interactions, and similar efficacy in all genotypes. This will offer clinicians new options as well as new challenges. A recent review addressed some of these anticipated issues, such as the off-label use of HCV medications and the roles of the FDA, consumer pressure, medical society guidelines, and third-party payers.[24]
The availability of these agents will provide unprecedented opportunities for off-label use of these therapies in many patients, including those with decompensated cirrhosis or chronic kidney disease, pediatric populations, and those with HIV coinfection. Because many of these populations represent relatively small numbers of patients with HCV, it may be difficult to accumulate the requisite data and possibly cost-prohibitive for manufacturers to apply for FDA approval.
The bottom line is that simpler, shorter, and safer strategies for treatment of patients infected with HCV are at hand.
http://www.medscape.com/viewarticle/815115_4
Friday, November 22, 2013
Simeprevir and Sofosbuvir-The Next Wave of Hepatitis C Treatment
Medscape Gastroenterology
The Next Wave of Agents for Treatment of Hepatitis C
William F. Balistreri, MD
November 21, 2013
For several years, the recommended standard of care for patients with chronic hepatitis C virus (HCV) infection consisted of a combination of pegylated interferon (PEG-IFN) and ribavirin (RBV). On the basis of understanding of the biology of the virus and identification of proteins involved in HCV replication came the development of agents that inhibited the HCV protease and polymerase enzymes.
A few years ago, the US Food and Drug Administration (FDA) approved 2 direct-acting antiviral agents for the treatment of HCV genotype 1: the NS3 protease inhibitors telaprevir and boceprevir. The American Association for the Study of Liver Diseases guidelines[1] were updated to recommend triple therapy consisting of one of these protease inhibitors given in combination with PEG-IFN and RBV. This recommendation was based on results of clinical trials of this combination, which showed significantly improved sustained virologic response (SVR) rates. Although this triple therapy is generally well tolerated, troublesome side effects occur in many patients. The good news is that the guidelines may once again be revised thanks to the emergence of the next wave of direct-acting antivirals.
Simeprevir and Sofosbuvir
Simeprevir is a potent, once-daily oral investigational NS3/4A protease inhibitor that was shown to be effective when coadministered with standard therapy (PEG-IFN and RBV) for treatment of HCV genotype 1 infection both in treatment-naive patients and in patients who did not respond to standard therapy.[2-10]
Primary efficacy and safety data from clinical trials of simeprevir in patients with genotype 1 chronic HCV infection were in part responsible for the recommended FDA approval of this agent on October 24, 2013. The FDA's Antiviral Drugs Advisory Committee recommendation was unanimous, commenting that the available data overwhelmingly supported approval of the simeprevir, PEG-IFN, and RBV combination for HCV genotype 1 infection in treatment-naive patients and in those who had relapse after previous therapy. The committee reviewed safety and efficacy data from a series of double-blind, placebo-controlled trials -- phase 3 studies of treatment-naive patients and patients with previous relapse, and a phase 2b study involving patients with previous relapse and nonresponders.
For example, simeprevir (TMC435) administered once daily in combination with PEG-IFN and RBV was associated with SVR 12 weeks after the end of treatment (SVR12) in approximately 80% of treatment-experienced (relapsed) genotype 1 chronic hepatitis C patients. The SVR12 rate was less than 40% in patients receiving placebo plus PEG-IFN and RBV. Treatment failure rates and relapse rates were lower in simeprevir recipients than placebo recipients.
Simeprevir was shown to be generally safe and well tolerated, even among patients with advanced liver fibrosis. The most common adverse events were fatigue, headache, and influenza-like illness.
The FDA Advisory Committee did, however, further recommend that patients be screened for the commonly occurring Q80K mutation because simeprevir was found to be less effective in the presence of this mutation. They also recommended that the label should indicate that sunburn is a common side effect. More information about the simeprevir clinical trials can be found at ClinicalTrials.gov.
Soon to follow was the recommended FDA approval of sofosbuvir, a nucleotide analog that inhibits NS5B-directed HCV replication; this agent has also been shown to be highly effective. Sofosbuvir in combination with standard therapy was associated with SVR12 rates of 90% compared with 58% in placebo-treated patients.[11,12]
Both agents will be indicated for treatment of patients with HCV genotype 1, but only in combination with PEG-IFN and RBV. These drugs represent an advance in management -- they promise to be capable of inducing high SVR rates with 1 pill per day, shorter duration of therapy, better tolerability, and no resistance development. The 1-pill-daily regimen simplifies the treatment strategy; however, the cost and side effects are likely to remain high.
A Glimpse of the Future in HCV Treatment
There is an even higher degree of optimism, however, because recent studies may usher in the next wave of treatment strategies for HCV infection. In my opinion, the goal for treatment in terms of efficacy, safety, and tolerability is an IFN-free regimen. Simeprevir is being studied in phase 2 IFN-free trials with and without RBV and in combination with a host of other agents that act synergistically to inhibit HCV replication, and which include all oral regimens. For example, studies in progress suggest that high SVRs can be achieved in patients treated with simeprevir and sofosbuvir together, with and without RBV.
I will end by offering a glimpse of the future. Currently under evaluation in clinical studies are second-generation protease inhibitors and small-molecule drugs that inhibit other viral enzymes. Drug cocktails that target multiple HCV enzymes simultaneously may ultimately become the standard of treatment, as in the current strategy for the management of infection with HIV.
The bottom line is that these exciting advances in antiviral therapy will lead to significant improvements in response rates with reduced adverse effects. These advantages may lower the threshold for HCV treatment for both patients and physicians.
It is important to note, though, that at present only a minority of HCV-infected patients may benefit because of multiple barriers that have been identified and that impede delivery of therapy. A major issue is inadequate case-finding, an obstacle that could be overcome by widespread screening. The Centers for Disease Control and Prevention recently advised enhanced testing; their guidelines state that many persons who test positive for hepatitis C do not receive the necessary follow-up to determine whether they require medical care. Therefore, enhanced efforts to improve awareness, education, and specialist availability are needed.
The high prevalence of HCV infection worldwide should also stimulate expanded efforts in primary prevention, including vaccine development. Perhaps we can soon wave good-bye to HCV!
http://www.medscape.com/viewarticle/814701_3
The Next Wave of Agents for Treatment of Hepatitis C
William F. Balistreri, MD
November 21, 2013
For several years, the recommended standard of care for patients with chronic hepatitis C virus (HCV) infection consisted of a combination of pegylated interferon (PEG-IFN) and ribavirin (RBV). On the basis of understanding of the biology of the virus and identification of proteins involved in HCV replication came the development of agents that inhibited the HCV protease and polymerase enzymes.
A few years ago, the US Food and Drug Administration (FDA) approved 2 direct-acting antiviral agents for the treatment of HCV genotype 1: the NS3 protease inhibitors telaprevir and boceprevir. The American Association for the Study of Liver Diseases guidelines[1] were updated to recommend triple therapy consisting of one of these protease inhibitors given in combination with PEG-IFN and RBV. This recommendation was based on results of clinical trials of this combination, which showed significantly improved sustained virologic response (SVR) rates. Although this triple therapy is generally well tolerated, troublesome side effects occur in many patients. The good news is that the guidelines may once again be revised thanks to the emergence of the next wave of direct-acting antivirals.
Simeprevir and Sofosbuvir
Simeprevir is a potent, once-daily oral investigational NS3/4A protease inhibitor that was shown to be effective when coadministered with standard therapy (PEG-IFN and RBV) for treatment of HCV genotype 1 infection both in treatment-naive patients and in patients who did not respond to standard therapy.[2-10]
Primary efficacy and safety data from clinical trials of simeprevir in patients with genotype 1 chronic HCV infection were in part responsible for the recommended FDA approval of this agent on October 24, 2013. The FDA's Antiviral Drugs Advisory Committee recommendation was unanimous, commenting that the available data overwhelmingly supported approval of the simeprevir, PEG-IFN, and RBV combination for HCV genotype 1 infection in treatment-naive patients and in those who had relapse after previous therapy. The committee reviewed safety and efficacy data from a series of double-blind, placebo-controlled trials -- phase 3 studies of treatment-naive patients and patients with previous relapse, and a phase 2b study involving patients with previous relapse and nonresponders.
For example, simeprevir (TMC435) administered once daily in combination with PEG-IFN and RBV was associated with SVR 12 weeks after the end of treatment (SVR12) in approximately 80% of treatment-experienced (relapsed) genotype 1 chronic hepatitis C patients. The SVR12 rate was less than 40% in patients receiving placebo plus PEG-IFN and RBV. Treatment failure rates and relapse rates were lower in simeprevir recipients than placebo recipients.
Simeprevir was shown to be generally safe and well tolerated, even among patients with advanced liver fibrosis. The most common adverse events were fatigue, headache, and influenza-like illness.
The FDA Advisory Committee did, however, further recommend that patients be screened for the commonly occurring Q80K mutation because simeprevir was found to be less effective in the presence of this mutation. They also recommended that the label should indicate that sunburn is a common side effect. More information about the simeprevir clinical trials can be found at ClinicalTrials.gov.
Soon to follow was the recommended FDA approval of sofosbuvir, a nucleotide analog that inhibits NS5B-directed HCV replication; this agent has also been shown to be highly effective. Sofosbuvir in combination with standard therapy was associated with SVR12 rates of 90% compared with 58% in placebo-treated patients.[11,12]
Both agents will be indicated for treatment of patients with HCV genotype 1, but only in combination with PEG-IFN and RBV. These drugs represent an advance in management -- they promise to be capable of inducing high SVR rates with 1 pill per day, shorter duration of therapy, better tolerability, and no resistance development. The 1-pill-daily regimen simplifies the treatment strategy; however, the cost and side effects are likely to remain high.
A Glimpse of the Future in HCV Treatment
There is an even higher degree of optimism, however, because recent studies may usher in the next wave of treatment strategies for HCV infection. In my opinion, the goal for treatment in terms of efficacy, safety, and tolerability is an IFN-free regimen. Simeprevir is being studied in phase 2 IFN-free trials with and without RBV and in combination with a host of other agents that act synergistically to inhibit HCV replication, and which include all oral regimens. For example, studies in progress suggest that high SVRs can be achieved in patients treated with simeprevir and sofosbuvir together, with and without RBV.
I will end by offering a glimpse of the future. Currently under evaluation in clinical studies are second-generation protease inhibitors and small-molecule drugs that inhibit other viral enzymes. Drug cocktails that target multiple HCV enzymes simultaneously may ultimately become the standard of treatment, as in the current strategy for the management of infection with HIV.
The bottom line is that these exciting advances in antiviral therapy will lead to significant improvements in response rates with reduced adverse effects. These advantages may lower the threshold for HCV treatment for both patients and physicians.
It is important to note, though, that at present only a minority of HCV-infected patients may benefit because of multiple barriers that have been identified and that impede delivery of therapy. A major issue is inadequate case-finding, an obstacle that could be overcome by widespread screening. The Centers for Disease Control and Prevention recently advised enhanced testing; their guidelines state that many persons who test positive for hepatitis C do not receive the necessary follow-up to determine whether they require medical care. Therefore, enhanced efforts to improve awareness, education, and specialist availability are needed.
The high prevalence of HCV infection worldwide should also stimulate expanded efforts in primary prevention, including vaccine development. Perhaps we can soon wave good-bye to HCV!
http://www.medscape.com/viewarticle/814701_3
Gilead's Sovaldi (sofosbuvir) and GSK drugs for HCV and HIV win EU green light
Title: European CHMP Adopts Positive Opinion for Gilead Sciences' Sovaldi® for the Treatment of Chronic Hepatitis C Infection
Date(s): 22-Nov-2013 8:47 AM
For a complete listing of our news releases, please click here
FOSTER CITY, Calif.--(BUSINESS WIRE)--Nov. 22, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has adopted a positive opinion on the company's Marketing Authorisation Application (MAA) for Sovaldi® (sofosbuvir 400 mg tablets), an investigational once-daily oral nucleotide analogue polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection in adults. The CHMP opinion supports the approval of Sovaldi for the treatment of HCV in combination with other agents. The CHMP's recommendation will now be reviewed by the European Commission, which has the authority to approve medicines for use in the 28 countries of the European Union (EU).
Chronic HCV is a major cause of liver cancer and liver transplantation in Europe and around the world. The current standard of care for HCV involves up to 48 weeks of therapy with a pegylated interferon (peg-IFN)/ ribavirin (RBV)-containing regimen. These regimens are not always effective and are associated with significant side effects and contraindications with other medicines. Many HCV patients in Europe are not considered appropriate candidates for current treatment options.
The CHMP opinion was adopted following an accelerated review procedure, which is reserved for medicinal products that are expected to be of major public health interest. This assessment does not guarantee marketing authorisation by the European Commission. However, if approved, Sovaldi could be available in the EU in the first quarter of 2014.
The MAA for Sovaldi is supported primarily by data from four Phase 3 studies, NEUTRINO, FISSION, POSITRON and FUSION in which 12 or 16 weeks of Sovaldi-based therapy was found to be superior or non-inferior to currently available treatment options or historical controls, based on the proportion of patients who had a sustained virologic response (were HCV undetectable) 12 weeks after completing therapy (SVR12). Patients who achieve SVR12 are considered cured of HCV. During the European review, data from two additional Phase 3 studies, VALENCE and PHOTON-1 were filed to the MAA. In the VALENCE study, patients with genotype 3 HCV infection were treated with Sovaldi and RBV for 24 weeks. The PHOTON-1 study evaluated Sovaldi and RBV for 12 weeks in patients with genotype 2 HCV infection co-infected with HIV-1 and for 24 weeks in patients with genotypes 1 or 3 HCV co-infected with HIV-1. In all Phase 3 studies of Sovaldi, no viral resistance to the drug was detected among patients who relapsed following completion of therapy.
To date, nearly 3,000 patients have received at least one dose of Sovaldi in Phase 2 or 3 studies. Sovaldi was well tolerated in clinical studies. Adverse events were generally mild and there were few treatment discontinuations due to adverse events. The most common adverse events occurring in at least 10 percent of patients were consistent with the safety profiles of peg-IFN and RBV and included fatigue, headache, nausea, insomnia, dizziness, pruritis (severe itching) and anemia.
In the United States, an expert advisory committee of the U.S. Food and Drug Administration (FDA) voted unanimously (15-0) on October 25, 2013 that the available data support approval of sofosbuvir. A final decision from the FDA is anticipated by December 8, 2013.
Sovaldi is an investigational product and its safety and efficacy have not been established.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.
Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risk of unfavorable results from ongoing and subsequent clinical trials of Sovaldi for HCV. The European Commission, FDA and other regulatory agencies may not approve Sovaldi in the currently anticipated timelines or at all, and any marketing approvals, if granted, may have significant limitations on their use. As a result, Sovaldi may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of Sovaldi if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended September 30, 2013, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
Sovaldi is a registered trademark of Gilead Sciences, Inc.
For more information on Gilead Sciences, please visit the company's website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
UPDATE 1-Gilead and GSK drugs for HCV and HIV win EU green light
Nov 22 (Reuters) - European regulators have recommended approval of a new drug for hepatitis C treatment from Gilead Sciences and an HIV medicine from GlaxoSmithKline, both of which are expected to be major sellers.
The European Medicine Agency (EMA) said on Friday its committee of experts also gave a green light to an Otsuka tuberculosis drug, following a review of an earlier rejection.
Analysts expect U.S.-based Gilead's sales to surge higher next year on the back of its new so-called HCV treatment known as Sovaldi, or sofosbuvir, for people infected with the liver-destroying hepatitis C virus.
Clinical trials of sofosbuvir in combination with other experimental oral Gilead drugs resulted in more than 95 percent of patients being cured.
GSK's Tivicay, or dolutegravir, is also forecast to be a significant new product for the British drugmaker. It will be sold through the ViiV Healthcare business, in which GSK is the biggest shareholder, alongside Pfizer and Shionogi .
In addition, the European agency recommended approval of a new a new two-in-one diabetes drug called Xigduo from Bristol-Myers Squibb and AstraZeneca.
Recommendations for marketing approval by the EMA's Committee for Medicinal Products for Human Use (CHMP) are normally endorsed by the European Commission within a couple of months.
http://www.reuters.com/article/2013/11/22/europe-medicines-idUSL5N0J72QT20131122
Date(s): 22-Nov-2013 8:47 AM
For a complete listing of our news releases, please click here
FOSTER CITY, Calif.--(BUSINESS WIRE)--Nov. 22, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has adopted a positive opinion on the company's Marketing Authorisation Application (MAA) for Sovaldi® (sofosbuvir 400 mg tablets), an investigational once-daily oral nucleotide analogue polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection in adults. The CHMP opinion supports the approval of Sovaldi for the treatment of HCV in combination with other agents. The CHMP's recommendation will now be reviewed by the European Commission, which has the authority to approve medicines for use in the 28 countries of the European Union (EU).
Chronic HCV is a major cause of liver cancer and liver transplantation in Europe and around the world. The current standard of care for HCV involves up to 48 weeks of therapy with a pegylated interferon (peg-IFN)/ ribavirin (RBV)-containing regimen. These regimens are not always effective and are associated with significant side effects and contraindications with other medicines. Many HCV patients in Europe are not considered appropriate candidates for current treatment options.
The CHMP opinion was adopted following an accelerated review procedure, which is reserved for medicinal products that are expected to be of major public health interest. This assessment does not guarantee marketing authorisation by the European Commission. However, if approved, Sovaldi could be available in the EU in the first quarter of 2014.
The MAA for Sovaldi is supported primarily by data from four Phase 3 studies, NEUTRINO, FISSION, POSITRON and FUSION in which 12 or 16 weeks of Sovaldi-based therapy was found to be superior or non-inferior to currently available treatment options or historical controls, based on the proportion of patients who had a sustained virologic response (were HCV undetectable) 12 weeks after completing therapy (SVR12). Patients who achieve SVR12 are considered cured of HCV. During the European review, data from two additional Phase 3 studies, VALENCE and PHOTON-1 were filed to the MAA. In the VALENCE study, patients with genotype 3 HCV infection were treated with Sovaldi and RBV for 24 weeks. The PHOTON-1 study evaluated Sovaldi and RBV for 12 weeks in patients with genotype 2 HCV infection co-infected with HIV-1 and for 24 weeks in patients with genotypes 1 or 3 HCV co-infected with HIV-1. In all Phase 3 studies of Sovaldi, no viral resistance to the drug was detected among patients who relapsed following completion of therapy.
To date, nearly 3,000 patients have received at least one dose of Sovaldi in Phase 2 or 3 studies. Sovaldi was well tolerated in clinical studies. Adverse events were generally mild and there were few treatment discontinuations due to adverse events. The most common adverse events occurring in at least 10 percent of patients were consistent with the safety profiles of peg-IFN and RBV and included fatigue, headache, nausea, insomnia, dizziness, pruritis (severe itching) and anemia.
In the United States, an expert advisory committee of the U.S. Food and Drug Administration (FDA) voted unanimously (15-0) on October 25, 2013 that the available data support approval of sofosbuvir. A final decision from the FDA is anticipated by December 8, 2013.
Sovaldi is an investigational product and its safety and efficacy have not been established.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.
Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risk of unfavorable results from ongoing and subsequent clinical trials of Sovaldi for HCV. The European Commission, FDA and other regulatory agencies may not approve Sovaldi in the currently anticipated timelines or at all, and any marketing approvals, if granted, may have significant limitations on their use. As a result, Sovaldi may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of Sovaldi if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended September 30, 2013, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
Sovaldi is a registered trademark of Gilead Sciences, Inc.
For more information on Gilead Sciences, please visit the company's website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
UPDATE 1-Gilead and GSK drugs for HCV and HIV win EU green light
Nov 22 (Reuters) - European regulators have recommended approval of a new drug for hepatitis C treatment from Gilead Sciences and an HIV medicine from GlaxoSmithKline, both of which are expected to be major sellers.
The European Medicine Agency (EMA) said on Friday its committee of experts also gave a green light to an Otsuka tuberculosis drug, following a review of an earlier rejection.
Analysts expect U.S.-based Gilead's sales to surge higher next year on the back of its new so-called HCV treatment known as Sovaldi, or sofosbuvir, for people infected with the liver-destroying hepatitis C virus.
Clinical trials of sofosbuvir in combination with other experimental oral Gilead drugs resulted in more than 95 percent of patients being cured.
GSK's Tivicay, or dolutegravir, is also forecast to be a significant new product for the British drugmaker. It will be sold through the ViiV Healthcare business, in which GSK is the biggest shareholder, alongside Pfizer and Shionogi .
In addition, the European agency recommended approval of a new a new two-in-one diabetes drug called Xigduo from Bristol-Myers Squibb and AstraZeneca.
Recommendations for marketing approval by the EMA's Committee for Medicinal Products for Human Use (CHMP) are normally endorsed by the European Commission within a couple of months.
http://www.reuters.com/article/2013/11/22/europe-medicines-idUSL5N0J72QT20131122
Friday, November 15, 2013
CME Video: Emerging Treatment Options for Hepatitis C Genotype 3,2 and 1 Patients
Hello folks, Clinical Care Options (CCO) launched a series of video modules with three different case scenarios exploring HCV treatment choices, durations, and outcomes in genotype 3, 2, and 1 patients.
For instance in the first module the panel weighs in on the clinical trial data of investigational agents sofosbuvir and simeprevir in treatment naïve and experienced genotype 3 patients. The text only for "Case 1 " is provided below, an expert video discussion for each case is available in the module.
Other topics include; treatment options for a new class of null responders who failed telaprevir or boceprevir and treating recurrent HCV after liver transplantation.
A free quick registration is required
Advanced HCV Treatment Topics
Fred Poordad, MD, moderates a case-based panel discussion exploring complex management issues in HCV-infected patients with Nezam H. Afdhal, MD, FRCPI, Douglas T. Dietrich, MD, Paul Y. Kwo, MD, and Norah Terrault, MD, MPH.
Released: 11/7/2013
Case 1: A Treatment-Experienced Patient With Genotype 3 HCV
Fred Poordad, MD:The patient is a 57-year-old white male with genotype 3a HCV infection and previous treatment failure on peginterferon 2a and ribavirin. He is now asking about his options for retreatment. He has no specific records of his past treatment, and his previous HCV RNA levels are unknown. He indicates he developed anemia while on therapy, with ribavirin being held for an unknown period. His current HCV RNA is 1.2 million IU/mL; liver enzyme studies determine his alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are elevated at 125 U/L and 114 U/L, respectively, but the rest of his laboratory examinations are within normal limits. His ultrasound shows his liver and spleen to be of normal size and a FibroTest identifies F0-F2 fibrosis.
The first consideration is whether you would perform any additional tests to evaluate the patient’s liver histology?
Douglas T. Dieterich, MD:I would certainly want more information because my own experience with FibroTest has been less than ideal. At my center, we typically use transient elastography because we have it available. I wouldn’t order a liver biopsy.
Paul Y. Kwo, MD:My view is that the results of a liver biopsy would be helpful. The serum markers present 1 part of the picture; however, in this instance, the management approach will depend on the liver histology, making the biopsy results very helpful.
Norah Terrault, MD, MPH:I agree that the patient’s fibrosis stage is critical information, and the F0-F2 score on the FibroTest leaves considerable room for uncertainty. The patient’s platelet count is also concerning. A biopsy may be useful to help determine whether to delay treatment.
It is important to remember that every test has an error rate, and all the available data have to come together and make sense when you evaluate a given patient. If 1 of the tests does not seem consistent with other aspects of the patient presentation, it is important to seek more information until you are confident in making the right decision.
Fred Poordad, MD:In this case, we did biopsy the patient, and the results indicated Stage 3 fibrosis by Metavir score.
Disease Outcomes and Treatment Outcomes in Genotype 3 HCV
Fred Poordad, MD:Until recently, genotype 2 and genotype 3 HCV have been classified as a single entity. However, in recent years, differences between these genotypes have become more clearly recognized. Disease progression rates are faster in genotype 3 compared with genotype 2.[1] As long ago as 2007, Shiffman and colleagues[2] demonstrated that patients with genotype 2 HCV treated with peginterferon/ribavirin experience an approximately 10% higher rate of sustained virologic response (SVR) compared with those infected with genotype 3 HCV with the same regimen. Importantly, rapid virologic response (RVR) rates are lower in genotype 3 and, especially in patients with genotype 3 without RVR, 16 weeks of therapy is inadequate to achieve SVR.[2] Further, patients experience higher relapse rates with genotype 3.[3]
Nezam H. Afdhal, MD, FRCPI:Disease progression rates are really a difficult question and determining disease progression rates is complex. There are no good cohort studies that have followed untreated patients for 20 or 30 years to show this kind of retrospective data. However, numerically speaking, patients with genotype 3 HCV infection tend to have more liver disease at the time of presentation—whether that means the true rate of progression is different or not is unclear. Additionally, genotype 3 HCV infection is associated with more hepatic steatosis; does that affect progression? Genotype 3 HCV infection in the United States and Europe is a disease of young intravenous (IV) drug users, while in the rest of the world it is very predominant in India and Pakistan, where there is significant morbidity and mortality associated with cirrhosis, liver cancer, and liver failure from this disease. Overall, we do see a lot more disease in patients with genotype 3 HCV infection, but I am not sure if this is due to a difference in the rate of progression in this patient population.
Norah Terrault, MD, MPH:I agree that it is difficult to judge disease progression, but there are some emerging data that the genotype might be a predictor of outcomes. Whether this outcome is driven by genotype 3 HCV itself or by accompanying cofactors is unclear.
Fred Poordad, MD:Van der Meer and colleagues[4] demonstrated an approximately 2-fold increased risk of mortality in patients with genotype 3 HCV infection compared with patients without genotype 3 infection. Importantly, curing genotype 3 HCV results in a significantly lower mortality rate compared with patients who are treated but do not achieve an SVR. Furthermore, older patients with genotype 3 HCV, higher levels of fibrosis, diabetes, or a history of alcohol use are less likely to do well.[4]
Douglas T. Dieterich, MD:That has been my experience as well. Alcohol, diabetes, and genotype 3 HCV infection are all associated with steatosis in the liver which may increase the fibrosis rate, leading to higher mortality. As a consequence, patients with genotype 3 HCV who fail treatment with peginterferon/ribavirin are some of the most difficult to treat outside of a clinical trial.
Emerging Treatment Options for Genotype 3 HCV
Fred Poordad, MD:The interferon-free combination of the nucleoside analogue sofosbuvir with ribavirin has shown promise in the treatment of genotypes 2 and 3 HCV, and at the time of writing has been submitted for approval for these genotypes.
The phase III Fission trial was a randomized, open-label, active-control, noninferiority study comparing 12 weeks of sofosbuvir plus ribavirin with 24 weeks of peginterferon/ribavirin in treatment-naive patients with genotype 2 or 3 HCV infection. The overall SVR rates were 67% for both sofosbuvir plus ribavirin and peginterferon/ribavirin.[5] Subanalysis based on HCV genotype found that patients with genotype 2 infection had a 97% SVR rate with sofosbuvir plus ribavirin compared with 78% SVR rate with peginterferon/ribavirin. However, the sofosbuvir plus ribavirin regimen for patients infected with genotype 3 HCV achieved an SVR of 56% vs a 63% SVR rate with peginterferon/ribavirin. These results indicate the noninferiority endpoint was met, but for genotype 3 HCV infection, the data are clearly not as satisfying as hoped.
The blinded, active-controlled phase III FUSION study explored treatment with 12 weeks of sofosbuvir plus ribavirin, followed by 4 weeks of matching placebo, or 16 weeks of sofosbuvir plus ribavirin in treatment-experienced patients with genotype 2 or 3 HCV infection. After 12 weeks of treatment in patients with genotype 3 HCV infection, the SVR rate was only 30%.[6] However, the additional 4 weeks of treatment doubled the SVR rate to 62%.
Now, go to the next page to see a video of the faculty discussion of these data.
Continue to CCO........
Watch - Sofosbuvir, ribavirin therapy after liver transplant shows positive results for HCV patients
Sofosbuvir, ribavirin therapy after liver transplant shows positive results for HCV patients
November 15, 2013
WASHINGTON — Combined sofosbuvir and ribavirin therapy to treat established recurrent hepatitis C infection after liver transplant has proven successful in preliminary results, according to research presented by Michael R. Charlton, MD, in a late-breaking abstract at The Liver Meeting.
The ongoing single-arm, open-label interferon-free pilot study enrolled 40 naive and treatment-experienced patients with recurrent HCV infection of any genotype after liver transplantation. The patients received up to 24 weeks of sofosbuvir and ribavirin with a primary endpoint of sustained virologic response 12 weeks after completion of treatment.
Full Story »
Wednesday, November 13, 2013
Costs for Hepatitis C Treatment Skyrocket
Medscape
Costs for Hepatitis C Treatment Skyrocket
WASHINGTON, DC — The expense of telaprevir-based triple therapy for hepatitis C — including adverse event management — is $189,000 per sustained viral response, report investigators.
"Our findings indicate that the benefit-cost ratio is lower than projected, based on results of the registration trials," lead investigator Andrea Branch, MD, from the Icahn School of Medicine at Mount Sinai in New York City.
Kian Bichoupan, MBS, who is Dr. Branch's first-year PhD clinical research student, presented the results here at The Liver Meeting 2013.
The number seemed to alarm session comoderator Sammy Saab, MD, from the David Geffen School of Medicine at UCLA, who called it "very surprising." It is "at least double what we think the cost is. I didn't know the cost of actually curing someone was so high," he said.
It is expected that 2 new direct-acting antiviral agents for the treatment of hepatitis C, simeprevir and sofosbuvir, will be approved by the US Food and Drug Administration (FDA) on December 8. Both have far better adverse-event profiles than telaprevir-based regimens, but the degree to which the cost-effectiveness calculation will change depends on their price, which hasn't yet been announced, Dr. Saab explained.
The benefit-cost ratio is lower than projected.
Before telaprevir received FDA approval in May 2011, the standard of care for genotype 1 hepatitis C was 48 weeks of pegylated interferon and ribavirin. With that regimen, the sustained viral response ranged from 40% to 50%. With the addition of telaprevir to the peginterferon and ribavirin regimen, response rates increased to 64% to 75%, but adverse events and costs also rose.
Previous studies have shown that peginterferon and ribavirin dual therapy costs $70,364 per sustained viral response in patients with genotype 1 hepatitis C. Data from phase 3 registration trials suggest that telaprevir-based triple therapy is cost-effective, but real-world data have been unavailable until now, Bichoupan said.
The researchers evaluated 147 patients who initiated telaprevir-based triple therapy at Mount Sinai. The mean age of the cohort was 56 years, and 68% of the cohort was male, 19% was black, 46% did not respond to previous hepatitis C treatment, and 35% had advanced fibrosis or cirrhosis.
They calculated the cost of the therapy itself and the management of adverse events from Medicare, the Agency for Healthcare Research and Quality, and other sources.
Sustained viral response was achieved by 44% of patients. At 48 weeks, the cost of telaprevir was $55,273, of peginterferon was $30,418, and of ribavirin for $4926. Telaprevir accounted for 61% of the $90,617 total, Bichoupan noted.
Adverse events, primarily anemia, accounted for 8% of the total cost; 48% of the patients required treatment with epoetin alpha, 9% needed blood transfusions, 8% were treated with granulocyte colony-stimulating factor (G-CSF), 13% required hospitalization, and 10% made emergency department visits.
Total costs were $664,083 for epoetin alfa, $29,007 for G-CSF, and $12,644 for transfusions.
The total cost of treating hepatitis C was higher for the 65 patients who achieved sustained viral response than for the 82 who did not ($6.33 vs $5.24 million).
The median cost per patient was $83,509. The researchers multiplied that by the reciprocal of the 44% sustained viral response (2.27), and arrived at $188,859 per response.
The cost per sustained viral response was lower for treatment-naïve than for previously treated patients ($158,403 vs $199,134). For patients with advanced liver fibrosis, the cost was $185,484. For those with less severe fibrosis, the cost jumped to $256,977, Bichoupan reported.
He pointed out that this study started when telaprevir had just reached the market, and that outcomes might improve over time with better strategies for preventing adverse events.
Dr. Branch told Medscape Medical News that these data can't determine whether nearly $200,000 per sustained viral response is cost-effective, because not enough is known about the cost savings associated with such a response.
Better Options
Other investigators have compared health costs for patients who achieve a sustained viral response with costs for patients with chronic hepatitis C infection. However, "this is not the best way to do the analysis because patients who achieve a sustained viral response may be healthier than patients who do not," Dr. Branch noted.
Dr. Saab said he agrees that the cost figures are likely to improve as experience with the drugs increases. However, he noted that telaprevir will likely disappear soon after the expected FDA approval of simeprevir and sofosbuvir.
Dr. Branch echoed this opinion. Telaprevir-based regimens "are only appropriate for patients who cannot wait even a few months for newer regimens to complete the FDA review and approval process," she said.
This study was supported in part by Gilead Sciences, the National Institute of Drug Abuse, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Saab is a consultant to Bristol-Myers Squibb.
The Liver Meeting 2013: American Association for the Study of Liver Diseases (AASLD). Abstract 244. Presented on November 5, 2013
Of Interest @ HCV New Drugs
How Much? A Battle Over The Cost Of The New Hepatitis C Drugs
According to an article over at Pharmalot, Wall Street has estimated sofosbuvir to reach $80,000 to $90,000, per patient in the US. The high cost will put these drugs out of reach for low and middle-income countries. Columnist Ed Silverman mentioned a presentation at this months liver meeting which suggests a much lower cost then predicted by investment analysts. Andrew Hill of Liverpool University and colleagues presented a new analysis of predicted minimum costs to produce four next generation HCV DAAs, currently in Phase 3 development. The poster was also presented earlier this year at the 7th IAS Conference. Here is the cost prediction in Hill's paper: $20-63 for a 12-week treatment of ribavirin, $10-30 for daclatasvir, $68-136 for sofosbuvir, $100-210 for faldaprevir and $130-270 for simeprevir (view the full analysis here)
Costs for Hepatitis C Treatment Skyrocket
WASHINGTON, DC — The expense of telaprevir-based triple therapy for hepatitis C — including adverse event management — is $189,000 per sustained viral response, report investigators.
"Our findings indicate that the benefit-cost ratio is lower than projected, based on results of the registration trials," lead investigator Andrea Branch, MD, from the Icahn School of Medicine at Mount Sinai in New York City.
Kian Bichoupan, MBS, who is Dr. Branch's first-year PhD clinical research student, presented the results here at The Liver Meeting 2013.
The number seemed to alarm session comoderator Sammy Saab, MD, from the David Geffen School of Medicine at UCLA, who called it "very surprising." It is "at least double what we think the cost is. I didn't know the cost of actually curing someone was so high," he said.
It is expected that 2 new direct-acting antiviral agents for the treatment of hepatitis C, simeprevir and sofosbuvir, will be approved by the US Food and Drug Administration (FDA) on December 8. Both have far better adverse-event profiles than telaprevir-based regimens, but the degree to which the cost-effectiveness calculation will change depends on their price, which hasn't yet been announced, Dr. Saab explained.
The benefit-cost ratio is lower than projected.
Before telaprevir received FDA approval in May 2011, the standard of care for genotype 1 hepatitis C was 48 weeks of pegylated interferon and ribavirin. With that regimen, the sustained viral response ranged from 40% to 50%. With the addition of telaprevir to the peginterferon and ribavirin regimen, response rates increased to 64% to 75%, but adverse events and costs also rose.
Previous studies have shown that peginterferon and ribavirin dual therapy costs $70,364 per sustained viral response in patients with genotype 1 hepatitis C. Data from phase 3 registration trials suggest that telaprevir-based triple therapy is cost-effective, but real-world data have been unavailable until now, Bichoupan said.
The researchers evaluated 147 patients who initiated telaprevir-based triple therapy at Mount Sinai. The mean age of the cohort was 56 years, and 68% of the cohort was male, 19% was black, 46% did not respond to previous hepatitis C treatment, and 35% had advanced fibrosis or cirrhosis.
They calculated the cost of the therapy itself and the management of adverse events from Medicare, the Agency for Healthcare Research and Quality, and other sources.
Sustained viral response was achieved by 44% of patients. At 48 weeks, the cost of telaprevir was $55,273, of peginterferon was $30,418, and of ribavirin for $4926. Telaprevir accounted for 61% of the $90,617 total, Bichoupan noted.
Adverse events, primarily anemia, accounted for 8% of the total cost; 48% of the patients required treatment with epoetin alpha, 9% needed blood transfusions, 8% were treated with granulocyte colony-stimulating factor (G-CSF), 13% required hospitalization, and 10% made emergency department visits.
Total costs were $664,083 for epoetin alfa, $29,007 for G-CSF, and $12,644 for transfusions.
The total cost of treating hepatitis C was higher for the 65 patients who achieved sustained viral response than for the 82 who did not ($6.33 vs $5.24 million).
The median cost per patient was $83,509. The researchers multiplied that by the reciprocal of the 44% sustained viral response (2.27), and arrived at $188,859 per response.
The cost per sustained viral response was lower for treatment-naïve than for previously treated patients ($158,403 vs $199,134). For patients with advanced liver fibrosis, the cost was $185,484. For those with less severe fibrosis, the cost jumped to $256,977, Bichoupan reported.
He pointed out that this study started when telaprevir had just reached the market, and that outcomes might improve over time with better strategies for preventing adverse events.
Dr. Branch told Medscape Medical News that these data can't determine whether nearly $200,000 per sustained viral response is cost-effective, because not enough is known about the cost savings associated with such a response.
Better Options
Other investigators have compared health costs for patients who achieve a sustained viral response with costs for patients with chronic hepatitis C infection. However, "this is not the best way to do the analysis because patients who achieve a sustained viral response may be healthier than patients who do not," Dr. Branch noted.
Dr. Saab said he agrees that the cost figures are likely to improve as experience with the drugs increases. However, he noted that telaprevir will likely disappear soon after the expected FDA approval of simeprevir and sofosbuvir.
Dr. Branch echoed this opinion. Telaprevir-based regimens "are only appropriate for patients who cannot wait even a few months for newer regimens to complete the FDA review and approval process," she said.
This study was supported in part by Gilead Sciences, the National Institute of Drug Abuse, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Saab is a consultant to Bristol-Myers Squibb.
The Liver Meeting 2013: American Association for the Study of Liver Diseases (AASLD). Abstract 244. Presented on November 5, 2013
Of Interest @ HCV New Drugs
How Much? A Battle Over The Cost Of The New Hepatitis C Drugs
According to an article over at Pharmalot, Wall Street has estimated sofosbuvir to reach $80,000 to $90,000, per patient in the US. The high cost will put these drugs out of reach for low and middle-income countries. Columnist Ed Silverman mentioned a presentation at this months liver meeting which suggests a much lower cost then predicted by investment analysts. Andrew Hill of Liverpool University and colleagues presented a new analysis of predicted minimum costs to produce four next generation HCV DAAs, currently in Phase 3 development. The poster was also presented earlier this year at the 7th IAS Conference. Here is the cost prediction in Hill's paper: $20-63 for a 12-week treatment of ribavirin, $10-30 for daclatasvir, $68-136 for sofosbuvir, $100-210 for faldaprevir and $130-270 for simeprevir (view the full analysis here)
Monday, November 11, 2013
AASLD Sofosbuvir/Simeprevir-What Is The Minimum costs to produce Hepatitis C Direct Acting Antivirals
Dec 9 - Fair Pricing Coalition Condemns Gilead Sciences on the High Price of New Hepatitis C Drug Sovaldi™, and Urges Rapid and Wide Dissemination of Support Program Details for Uninsured and Underinsured People Living with Hepatitis C Nov 26 - Now FDA Approved Olysio (simeprevir) - The New Kid On The Block
OLYSIO (Simeprevir) Cost? - Janssen has priced Olysio at a wholesale acquisition price of $22,120 per bottle of 28 capsules (150 mg capsules), which is an approximately one-month supply. That's roughly $66,360 for a three-month course.
Nov 13 -Medscape - Costs for Hepatitis C Treatment Skyrocket
AASLD-What Is The Minimum costs to produce Hepatitis C Direct Acting Antivirals
A third wave of anti HCV DAA agents are currently moving through the pipeline, two new DAAs have already been reviewed by the Antiviral Drugs Advisory Committee, Gilead's Sofosbuvir and Johnson & Johnson's Simeprevir.
The result of the whole process is expected to be decided by the FDA in early December for Sofosbuvir and late November for Simeprevir.
Additionally, other new DAAs in Phase III clinical trials are able to increase SVR and shorten therapy in a significant proportion of both treatment-naïve and treatment-experienced chronic HCV infected patients.
However the drugs are expected to be expensive, patients in the US could pay anywhere from $60,000 - $100,000 per treatment. The cost for these life saving drugs will be out of reach for patients in developing countries and the uninsured.
Analysis Of Predicted Minimum Costs To Produce Hepatitis C Direct Acting Antivirals
At this months AASLD, Andrew Hill of Liverpool University and colleagues presented a new analysis of predicted minimum costs to produce Direct Acting Antivirals for the treatment of hepatitis C. The minimum cost of 12 weeks of treatment with each DAA(see below) was calculated assuming a production cost per gram of HCV DAA between 1-10 times the equivalent HIV antiretroviral and based on compound properties including chemical structure, complexity of synthesis, and daily dose. The analysis was also presented earlier this year at the 7th IAS Conference
Predicted Minimum Costs
The analysis predicted $20-63 for a 12-week treatment of ribavirin, $10-30 for daclatasvir, $68-136 for sofosbuvir, $100-210 for faldaprevir and $130-270 for simeprevir see charts below.
The complete analysis is available for downloading here or view the predicted costs/slides provided below.
AASLD, Washington DC
Minimum costs to produce Hepatitis C Direct Acting Antivirals
Andrew Hill and Saye Khoo, Department of Pharmacology and Therapeutics, Liverpool University, UK Bryony Simmons, Imperial College, London, UK Nathan Ford, University of Cape Town, South Africa
64th Annual Meeting of AASLD, Washington DC, United States of America, November 2013 [Poster 1097]
TREATMENT COVERAGE IS LOW EVEN IN DEVELOPED COUNTRIES
Despite the long term morbidity & mortality associated with untreated hepatitis C, data suggests that relatively few patient are being treated.
In Europe only 3.5% of infected individuals received antiviral treatment by the end of 2010 (ranging from 16% in France to <1% in Poland)
In the USA only 21% of infected individuals had received treatment by the end of 2007
Reasons for under - treatment:
• Under - diagnosis (80% of HCV cases are asymptomatic)
• Limitations of currently available medication
• The very high prices of drug treatment
THE STIMATED COST OF CURRENT TREATMENT (UK & US ESTIMATES )
HEPATITIS C GLOBAL PREVALENCE BY COUNTRY (2010)
PATENT EXPIRY DATES
DAA COMBINATIONS : INTERFERON - FREE REGIMENS
Several combinations of two DAAs (with or without RBV) can cure HCV (SVR) in the
majority of treatment
-
naïve, genotype 1 patients, without the use of interferon:
Continued......
RATIONALE
DAAs for HCV infection have similar mechanisms of action and chemical structures to antiretrovirals for HIV infection.
Generic antiretrovirals are currently manufactured at very low cost, for treatment of over ten million people with HIV in low and middle income countries.
Minimum costs of HIV antiretrovirals are 0.2-0.9/g of drug for nucleoside analogues, 0.5/g for nucleotide analogues, and 0.7-2.1/g for protease inhibitors.
For widespread treatment of HCV in developing countries to be feasible, we need short-course of antiviral treatment available at very low cost.
Using the cost of HIV drugs as a framework, we can make estimates for the potential cost of HCV DAAs
Commentary/Abstracts/Videos @ Healio
Capsule Summaries, review by experts and slides @ Clinical Care Options CCO
Commentary/Abstracts with coverage by Liz Highleyman @ hivandhepatitis.com
Slides/Abstracts @ NATAP
CME/CE with commentary by Michael Smith @ MedPage Today
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