Real life Dallas Buyers Club operation helps hepatitis C patients with free drugs

Real life Dallas Buyers Club operation helps hepatitis C patients with free drugs

Richard Woolveridge

Since the FixHepC Buyers Club was started by father-and-son team Dr John and Dr James Freeman, tens of thousands of people in more than 100 countries have made several million visits to the fixhepc.com website.

"At least 50 patients a week have signed up to get the drugs they need with the help of the club," Dr Freeman said.

"There's tremendous community spirit in Australia and we're getting patients saying, 'Look I'm not wealthy but I can afford to help out someone else with hep C. Let me donate the price of a course of pills for someone who can't pay'. "

Read more: http://www.smh.com.au/nsw/real-life-dallas-buyers-club-operation-helps-hepatitis-c-patients-with-free-drugs-20151128-glamtm.html#ixzz3sydVSafU
Follow us: @smh on Twitter | sydneymorningherald on Facebook

Of Interest - November Updates
Reducing the cost of new hepatitis C drugs
An index of articles pointing the reader to the current controversy over the high price of Sovaldi, Harvoni (ledipasvir/sofosbuvir) and AbbVie Viekira Pak.

Functional Human Liver Cells Grown in the Lab

Functional Human Liver Cells Grown in the Lab

26/11/2015

German-Israeli partnership develops a library of highly functional liver cells from varying genetic backgrounds for scientific, clinical and pharmaceutical development
In new research appearing in the prestigious journal Nature Biotechnology, an international research team led by The Hebrew University of Jerusalemdescribes a new technique for growing human hepatocytes in the laboratory. This groundbreaking development could help advance a variety of liver-related research and applications, from studying drug toxicity to creating bio-artificial liver support for patients awaiting transplantations.

The liver is the largest internal organ in the human body, serving as the main site of metabolism. Human hepatocytes – cells that comprise 85% of the liver – are routinely used by the pharmaceutical industry for study of hepatotoxicity, drug clearance and drug-drug interactions. They also have clinical applications in cell therapy to correct genetic defects, reverse cirrhosis, or support patients with a liver-assist device.

Regrettably, while the human liver can rapidly regenerate in vivo, recognized by the ancient Greeks in the myth of Prometheus, this capability to proliferate is rapidly lost when human cells are removed from the body. Thus far, attempts to expand human hepatocytes in the laboratory resulted in immortalized cancer cells with little metabolic function. The scarce supply of human hepatocytes and this inability to expand them without losing function is a major bottleneck for scientific, clinical and pharmaceutical development.

To address this problem, Prof. Yaakov Nahmias, director of the Alexander Grass Center for Bioengineering at the Hebrew University of Jerusalem, partnered with leading German scientists at upcyte technologies GmbH(formerly Medicyte) to develop a new approach to rapidly expand the number of human liver cells in the laboratory without losing their unique metabolic function.

Based on early work emerging from the German Cancer Research Center (DKFZ) on the Human Papilloma Virus (HPV), the research team demonstrated that weak expression of HPV E6 and E7 proteins released hepatocytes from cell-cycle arrest and allowed them to proliferate in response to Oncostatin M (OSM), a member of the interleukin 6 (IL-6) superfamily that is involved in liver regeneration. Whereas previous studies caused hepatocytes to proliferate without control, turning hepatocytes into tumor cells with little metabolic function, the researchers carefully selected colonies of human hepatocytes that only proliferate in response to OSM. Stimulation with OSM caused cell proliferation, with doubling time of 33 to 49 hours. Removal of OSM caused growth arrest and hepatic differentiation within 4 days, generating highly functional cells. The method, described as the upcyte© process (upcyte technologies GmbH), allows expanding human hepatocytes for 35 population doubling, resulting in 1015 cells (quadrillion) from each liver isolation. By comparison, only 109 cells (billion) can be isolated from a healthy organ.

“The approach is revolutionary,” said Dr. Joris Braspenning, who led the German group. “Its strength lies in our ability to generate liver cells from multiple donors, enabling the study of patient-to-patient variability and idiosyncratic toxicity.” The team generated hepatocyte lines from ethnically diverse backgrounds that could be serially passaged, while maintaining CYP450 activity, epithelial polarization, and protein expression at the same level as primary human hepatocytes. Importantly, the proliferating hepatocytes showed identical toxicology response to primary human hepatocytes across 23 different drugs.

“This is the holy grail of liver research,” said Prof. Nahmias, the study’s lead author. “Our technology will enable thousands of laboratories to study fatty liver disease, viral hepatitis, drug toxicity and liver cancer at a fraction of the current cost.” Nahmias noted that genetic modifications preclude using the cells for transplantation, “but we may have found the perfect cell source for the bio-artificial liver project.”

The proliferating hepatocyte library was recently commercialized by upcyte technologies GmbH (Hamburg, Germany), which is expanding the scope of the technology. “upcyte© hepatocytes represent the next generation of cell technology”, said Dr. Astrid Nörenberg, the company’s managing director. “We are poised to become the leading cell supplier for pharmaceutical development and chemical toxicity testing.”

Yissum, the Research and Development Company of the Hebrew University, and upcyte technologies GmbH submitted a joint patent application earlier this year and are actively seeking investment.

Collaborating researchers on this study are affiliated with the Alexander Grass Center for Bioengineering, The Hebrew University of Jerusalem; upcyte technologies GmbH; Tel Aviv Sourasky Medical Center and Tel-Aviv University.

Support for this research came from the Förderprogram Biotechnologie Baden-Würtenberg (project N° 720.830-4-03), European Research Council Starting Grant TMIHCV (project N° 242699), HeMiBio: a jointly funded consortium by the European Commission and Cosmetics Europe as part of the SEURAT-1 cluster (project N° HEALTH-F5-2010-266777) and ReLiver a European Union Seventh Framework Program (FP7/2007-2013) under grant agreement n° 304961.

CITATION: Long-term culture and expansion of primary human hepatocytes. Gahl Levy, David Bomze, Stefan Heinz, Sarada Devi Ramachandran, Astrid Noerenberg, Merav Cohen, Oren Shibolet, Ella Sklan, Joris Braspenning & Yaakov Nahmias. Nature Biotechnology (2015) doi:10.1038/nbt.3377. http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.3377.html

Happy Thanksgiving

Happy Thanksgiving 

HCV: 4 Weeks Too Short for Treatment With New Drugs

Medscape Medical News

HCV: 4 Weeks Too Short for Treatment With New Drugs
Veronica Hackethal, MD
November 24, 2015

Four weeks of triple or quadruple combination therapy using new drugs for hepatitis C virus (HCV) results in only limited cure rates in patients with early-stage liver fibrosis, according to a study published online November 23 in the Annals of Internal Medicine.

"In this proof-of-concept study involving treatment-naive noncirrhotic patients with chronic HCV genotype 1 infection, 4 weeks of treatment with ledipasvir, sofosbuvir, and GS-9451 with or without GS-9669 was well-tolerated; however, only 30% (15 of 50) of patients achieved [a sustained viral response at 12 weeks]," write Anita Kohli, MD, from the University of Maryland, Baltimore, and colleagues "Thus, a treatment duration of 4 weeks with 3 or 4 potent [direct-acting antivirals] is not sufficient to cure HCV infection in most patients."

Current treatment regimens for HCV require 12 or more weeks of therapy. Shorter-term regimens have the potential to simplify therapy, increase adherence, reduce toxicity, and increase cost-effectiveness.

A previous study with the investigational drugs GS-9451 (a protease inhibitor) and GS-9669 (a nonnucleoside polymerase inhibitor), combined with ledipasvir and sofosbuvir, showed a sustained viral response rate of 95% (39 of 40 patients) in just 6 weeks.

To try to abbreviate therapy further, Dr Kohli and colleagues designed the current trial. The open-label nonrandomized phase 2a trial took place at the National Institutes of Health Clinical Center in Bethesda, Maryland, from January 2014 to May 2015. It included mostly African Americans (76%; 38/50), who are disproportionately affected by the HCV epidemic. Participants had not been previously treated and had early-stage liver fibrosis. Most were male (72%; 36/50) and had HCV 1a genotype (68%; 34/50).

Researchers divided participants sequentially into two groups. Twenty-five participants received a triple drug regimen of ledipasvir and sofosbuvir plus GS-9451 for 4 weeks. The second group of 25 participants received the four-drug regimen of ledipasvir, sofosbuvir, GS-9451, and GS-9669 for 4 weeks. Dosages included ledipasvir 400 mg and sofosbuvir 90 mg as a single combination tablet taken once daily, GS-9451 80 mg once daily, and GS-9669 250 mg once daily. All but one patient completed the trial.

Among participants in the triple-drug group, 10 patients (40%; 95% confidence interval [CI], 21% - 61%) reached a sustained viral response at 12 weeks, defined as unquantifiable HCV RNA levels at week 12, as did five patients (20%; 95% CI, 7% - 41%) in the four-drug group.

At baseline, 10 participants had HCV variants that increased resistance to at least one of the antivirals in the study. All these participants experienced viral relapse.

Adverse events, mostly mild, occurred among 48% (12/25) of patients in the triple-drug group and 72% (18/25) in the four-drug group. None of the patients discontinued therapy because of adverse events.

Lower baseline viral load, younger age, HCV genotype 1b, and absence of resistance mutations were linked to increased likelihood of a sustained viral response at 12 weeks. This subgroup may achieve acceptable response rates using a 4-week regimen, the authors suggest, and the possibility warrants further investigation.


"Our data suggest that for most patients, a treatment duration longer than 4 weeks is required to achieve [a sustained viral response]," they conclude. "However, some patients are capable of achieving [a sustained viral response] with 4 weeks of therapy, which could be attributable to the presence of several favorable factors, such as early fibrosis, low viral burden, and absence of [resistance-associated variables]."

The nonrandomized nature of the study and small sample size could have limited the study.

One or more coauthors reports research agreements, grants, personal fees, and/or stock ownership in one or more of the following: National Institutes of Health, Gilead Sciences, Merck, Pfizer, Johnson & Johnson, and Bristol-Myers Squibb. Two coauthors were employees of Gilead Sciences.

Ann Intern Med. Published online November 24, 2015. Abstract

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Keeping Up With Rapid Advances in Hepatitis C Treatment

Keeping Up With Rapid Advances in Hepatitis C Treatment 

Pharmacy Practice News
ISSUE: NOVEMBER 2015 | VOLUME: 42

At the 2015 American College of Clinical Pharmacy’s Global Conference on Clinical Pharmacy, Linda Spooner, PharmD, BCPS (AQ-ID), FASHP, a professor of pharmacy practice at Massachusetts College of Pharmacy and Health Sciences University, in Worcester, provided an overview of what pharmacists need to know.

Drug interaction assessments are critical, because some of the new medications won’t work when taken with certain drugs. For example, the fixed-dose combination ombitasvir-paritaprevir-ritonavir plus dasabuvir (Viekira Pak, AbbVie) is most susceptible to drug interactions with immunosuppressants and antiretroviral therapy, mainly due to the influence of ritonavir on multiple enzymes (Ann Pharmacother 2015;49[6]:674-687).

Read more...

Hepatitis C - NICE publishes final drug recommendations for the treatment of four separate medical conditions

NICE publishes final drug recommendations for the treatment of four separate medical conditions

The National Institute for Health and Care Excellence (NICE) has published its final recommendations on whether six different drug treatments should be routinely funded by the NHS.

Each piece of guidance looked at the cost-effectiveness of a particular drug to treat a specific medical condition. They cover major depressive disorder, hepatitis C, melanoma and psoriasis.

Vortioxetine for the treatment of major depressive disorder

NICE recommends vortioxetine be made available as a third-line treatment for major depressive episodes. 

Vortioxetine (marketed as Brintellix by Lundbeck and Takeda) should be considered as a treatment option for adults whose condition has responded inadequately to two antidepressants within the current episode.

New options for hepatitis C

NICE recommends three new treatments for some adults with hepatitis C:
Ledipasvir-sofosbuvir (Harvoni, Gilead Sciences)
Ombitasvir-paritaprevir-ritonavir with or without dasabuvir (Viekirax with or without Exviera, Abbvie)
Daclatasvir (Daklinza, Bristol-Myers Squibb)

It is recommended that the decision to treat and prescribing decisions are made by multidisciplinary teams in the operational delivery networks put in place by NHS England, to prioritise treatment for people with the highest unmet clinical need.

Pembrolizumab for the treatment of melanoma

NICE recommends pembrolizumab (also called Keytruda and manufactured by Merck, Sharp & Dohme) as a treatment for some patients with advanced melanoma. It is recommended as an option in adults:
for treating advanced melanoma that has not been previously treated with ipilimumab, and
when the company provides pembrolizumab with the discount agreed in the patient access scheme.

Apremilast for the treatment of Psoriasis

NICE does not recommend apremilast (also called Otezla and manufactured by Celgene) for treating some adults with moderate to severe chronic plaque psoriasis.

People whose treatment with apremilast was funded by the NHS before this guidance was published should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.

Source https://www.nice.org.uk/news/press-and-media/nice-publishes-final-drug-recommendations-for-the-treatment-of-four-separate-medical-conditions

Trinity Scientists Homing in on New Hepatitis C Vaccine

Trinity Scientists Homing in on New Hepatitis C Vaccine

23 November 2015

Trinity researchers have just commenced a major new study to evaluate a new vaccine for the prevention of Hepatitis C infection in HIV patients, who are at increased risk of contracting the common infection.

Around 180 million people worldwide and an estimated 20,000 to 50,000 people in Ireland have Hepatitis C. It is a blood borne viral infection which is spread through direct contact with the blood of an infected individual and can lead to fibrosis (scarring of the liver), liver failure and cancer. Currently, there is no effective vaccine available for Hepatitis C and treatment is costly, often in the region of €50,000 per individual, lengthy, associated with side effects and is not 100% effective.

Numerous recent outbreaks of Hepatitis C in HIV-infected individuals internationally have highlighted the urgent need for a vaccine to prevent infection. HIV-infected individuals are at increased risk of Hepatitis C infection due to similar routes of acquisition. Hepatitis C infection also progresses more rapidly to liver damage in HIV-infected individuals. Approximately 20-30% of people with HIV are co-infected with Hepatitis C.

“A safe, affordable and effective vaccine for Hepatitis C would have a huge impact on combatting Hepatitis C given the multitude of people who are unaware of their diagnosis and represent a potential source for new infections,” said Dr Ciaran Bannan, a research fellow in Trinity College Dublin and the Department of GU Medicine and Infectious Diseases at St James’ Hospital who is leading the research with Professor Colm Bergin, Clinical Professor of Infectious Diseases, School of Medicine.

The study, which is the first phase-1 vaccine study in HIV infected people in Ireland, is also the first of a planned number of early intervention studies to be carried out in the Wellcome Trust-HRB Clinical Research Facility, a joint enterprise between Trinity College Dublin and St James’s Hospital.

The research team are evaluating the safety and the ability of a new vaccine to produce an immune response against Hepatitis C. Previous healthy volunteer studies in the University of Oxford have shown encouraging results. If effective, this vaccine could also be made available to other high risk groups such as intravenous drug users.

The study, which will run for 20 months, will follow 20 patients have in Dublin and St Gallen, Switzerland. Patients will be given two vaccines eight weeks apart and then followed closely to assess safety and the development of immune responses to Hepatitis C following vaccination. The vaccines being tested in this study are called AdCh3NSmut1 and MVA-NSmut and have been developed by ReiThera Srl and GlaxoSmithKline Biologicals SA.

This study is the result of collaboration between the University of Oxford, Kantonsspital, St. Gallen and GlaxoSmithKline Biologicals SA and has been funded by an EU Seventh Framework Program (FP7) grant.

http://www.tcd.ie/news_events/articles/trinity-scientists-homing-in-on-new-hepatitis-c-vaccine/6173#.VlYIv3arTrd

AbbVie's TECHNIVIE™ Receives Health Canada Approval for Genotype 4 Chronic Hepatitis C Infection

AbbVie's TECHNIVIE™ Receives Health Canada Approval for Genotype 4 Chronic Hepatitis C Infection

TECHNIVIE provides an opportunity to treat adults who have genotype 4 (GT4) chronic hepatitis C virus (HCV) infection without cirrhosis, a population historically considered difficult-to-treat

TECHNIVIE is the first and only all-oral, interferon-free, direct-acting antiviral treatment approved in Canada for adult patients with GT4 chronic HCV infection

Approval is supported by a Phase II clinical trial of 135 chronic HCV GT4 patients, which demonstrated 100 percent sustained virologic response rates at 12 weeks post-treatment (SVR ₁₂) in patients who took TECHNIVIE with ribavirin (RBV)

MONTREAL, Nov. 24, 2015 /CNW/ - AbbVie, a global, biopharmaceutical company, today announced that Health Canada granted a Notice of Compliance (NoC) to TECHNIVIE (ombitasvir/paritaprevir/ritonavir tablets) in combination with ribavirin (RBV) for the treatment of adults with genotype 4 (GT4) chronic hepatitis C virus (HCV) infection without cirrhosis who are either treatment naïve or previously treated with peginterferon and ribavirin.

"Over the last several years, there has been a major focus on hepatitis C genotype 1 disease. The optimal protocol for treating hepatitis C genotype 4 patients was not well defined. As a practicing hepatologist, I am thrilled that finally there is a cure for people living with hepatitis C genotype 4, which is relatively hard to eradicate," explains Dr. Magdy Elkhashab, Gastroenterologist/Hepatologist, Director of the Toronto Liver Centre. "This new therapy, which is given orally, can cure the disease in genotype 4 patients in almost 100% of cases. These are really exciting times. When I started my practice 20 years ago, I saw cure rates of 4 to 6%. I can truly say that I have seen the whole hepatitis C story unfold."

HCV GT4 has historically been difficult to treat. Egypt has the highest prevalence with more than 90% of infections due to genotype 4. Genotype 4 has been spreading in several Western countries, including Canada, due to variations in population structure, immigration, routes of transmission, travel and tourism. 1,2

"The approval of TECHNIVIE by Health Canada is further proof of AbbVie's ongoing commitment to help address the burden of hepatitis C. We are determined to provide best-in-class solutions for people living with hepatitis C in Canada, especially through our support program AbbVie Care," said Stéphane Lassignardie, general manager, AbbVie Canada.

Virologic cure is defined as a sustained virologic response (SVR), which is when the virus is no longer detectable in the patient's blood 12 weeks after treatment (SVR12).3

About the PEARL-I Study
This approval of TECHNIVIE is based on data from the PEARL-I study, which demonstrated 100 percent sustained virologic response rates at 12 weeks post-treatment (SVR12) in patients who received TECHNIVIE and RBV for 12 weeks. PEARL-I is an open-label Phase 2b study that evaluated the efficacy and safety of TECHNIVIE in GT4 chronic HCV patients without cirrhosis. The study included GT4 patients who were new to therapy (n=42/42) or who had failed previous treatment with pegylated interferon (pegIFN) and RBV (n=49/49). Additionally, 91 percent of patients who were new to therapy achieved SVR12 (n=40/44) after taking TECHNIVIE without RBV. In the treatment-naïve group without RBV, on-treatment virologic failure was reported in one patient (two percent), and two patients (five percent) experienced post-treatment relapse. There were no virologic failures in the other treatment arms.

There were no discontinuations due to adverse events in these patients. The most commonly reported treatment-emergent adverse events (greater than 10 percent) observed in patients receiving TECHNIVIE with RBV were asthenia, fatigue, and headache.

About TECHNIVIE
TECHNIVIE is an all-oral antiviral treatment consisting of the fixed-dose combination of ombitasvir/paritaprevir/ritonavir (12.5/75/50 mg) taken as 2 tablets once daily and taken with food, which is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice daily), taken with food. The combination of two direct-acting antivirals, each with distinct mechanisms of action, targets and inhibits specific HCV proteins in the viral replication process.

About AbbVie Care
Canadians prescribed TECHNIVIE will have the opportunity to be enrolled in AbbVie Care, AbbVie's signature care program. AbbVie Care provides support to people living with hepatitis C. The program is designed to provide a wide range of customized services including reimbursement and financial support, pharmacy services coordination with pharmacies trained in hepatitis C, lab work reminders and coordination, personalized education and ongoing disease management support throughout the treatment and beyond.

For more information, call 1-844-471-CARE (2273) or consult www.abbviecare.ca.

Important Safety Information4

TECHNIVIE (ombitasvir/paritaprevir/ritonavir tablets) is a prescription medicine used with ribavirin to treat adults with genotype 4 chronic (lasting a long time) hepatitis C (hep C) virus infection without cirrhosis.

To help avoid side effects and make sure you are using your medicines correctly, talk to your doctor before you take TECHNIVIE. Talk about any health problems you may have, including if you:
are taking birth control medicines of any kind or using a medicine that has ethinyl estradiol. Ethinyl estradiol is usually found in birth control pills. However, not all birth control pills have ethinyl estradiol. You must not use medicines that have ethinyl estradiol while taking TECHNIVIE. Your doctor will ask you to stop or change to a different type of birth control while you are taking TECHNIVIE.
have had a liver transplant.
have liver problems other than HCV infection.
are breastfeeding or plan to breastfeed. It is not known if TECHNIVIE passes into your breast milk. You and your doctor should decide if you will take TECHNIVIE or breastfeed. You should not do both.

Pregnancy and Birth Control
Females must have a negative pregnancy test before starting TECHNIVIE and ribavirin, every month while on the medicine, and for 6 months after stopping them.
You or your partner should not become pregnant while taking TECHNIVIE with ribavirin and for 6 months after you have stopped taking them.
You and your partner must use 2 kinds of birth control while taking TECHNIVIE and ribavirin and for 6 months after you have stopped taking them.
Talk to your doctor about the kind of birth control that you can use.
If you or your partner becomes pregnant while taking TECHNIVIE and ribavirin or within 6 months after you stop taking them, tell your doctor right away.

Other warnings you should know about:
Rises in liver tests have occurred when TECHNIVIE was taken in studies. Contact your doctor right away if you have symptoms like those listed below since these may mean you have a serious problem with your liver:
loss of appetite (do not feel like eating),
stomach ache,
nausea (feeling sick in the stomach),
vomiting,
feeling tired or weak,
yellowing of the skin and eyes,
dark urine and pale stool.

It is not known if taking TECHNIVIE is safe or will work in children under 18 years of age.
Your doctor may do blood tests before you start taking, and while you are on your medicines. This is to help check if the medicines are working for you.

Tell your doctor all the medicines, drugs, vitamins and minerals, natural supplements or alternative medicines you are already taking, as interactions are possible with TECHNIVIE.

The complete TECHNIVIE Product Monograph is available on the manufacturer's websitewww.abbvie.ca, or by calling 1-888-704-8271.

Additional information about AbbVie's chronic hepatitis C clinical program can be found onwww.clinicaltrials.gov.

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.ca and www.abbvie.com. Follow @abbvieon Twitter or view careers on our Facebook or LinkedIn page.

1 CATIE.
http://www.catie.ca/en/treatmentupdate/treatmentupdate-202/hepatitis-c-virus/simeprevir-interferon-ribavirin-hcv-genotype-4
Accessed on November 10, 2015

2 PUBMED. Hepatitis C genotype 4: What we know and what we don't yet know. Kamal SM, Nasser IA.
http://www.ncbi.nlm.nih.gov/pubmed/18240152
Accessed on November 10, 2015

3 AASLD/IDSA/IAS–USA. When and in Whom to Initiate HCV Therapy.
http://www.hcvguidelines.org/full-report/when-and-whom-initiate-hcv-therapy
Accessed on November 10, 2015

4 TECHNIVIE (ombitasvir/paritaprevir/ritonavir tablets) Product Monograph. Date of Preparation:October 20, 2015
http://www.abbvie.ca/content/dam/abbviecorp/ca/english/docs/TECHNIVIE_PM_EN.pdf
Accessed on November 10, 2015

Expensive drugs that cure hepatitis C are worth the cost, even at early stages of liver fibrosis

Related: November 2015 Updates
Reducing the cost of new hepatitis C drugs

An index of articles pointing the reader to the current controversy over the high price of Sovaldi, Harvoni (ledipasvir/sofosbuvir) and AbbVie Viekira Pak.

Expensive drugs that cure hepatitis C are worth the cost, even at early stages of liver fibrosis

UNIVERSITY OF CALIFORNIA - SAN FRANCISCO

It is worthwhile to give patients expensive new drugs that can cure their hepatitis C much earlier than some insurers are now willing to pay for them, according to a UC San Francisco study that models the effects of treating the disease early versus late in its development.

Researchers said they were surprised by the findings, since the drugs can cost up to $100,000 for a full course of treatment. But when they factored in the long-term medical cost of delaying treatment for hepatitis C, they found the savings, in combination with improvements in the quality of patients' lives, were enough under current standards to justify using them even at early stages of liver fibrosis. Researchers said the drugs were therefore cost effective.

Cost effectiveness is a measure of broad social benefit that health economists use to make decisions about whether medical treatments are warranted. The researchers said the balance was tipped in favor of the drugs because the hepatitis C virus can cause so much damage. Hepatitis C is one of the leading causes of liver cancer, liver transplants and liver-related death, yet the drugs can prevent much of that with an early cure. Moreover, even if costly hepatitis C treatments are delayed, they eventually will be given to many patients once the infection causes enough damage to their livers.

About 3.2 million people have hepatitis C in the United States. The vast majority were infected by blood transfusions before testing of blood donors became available in 1992. Today, most people get infected from injecting drugs.

Left unchecked, hepatitis C causes varying degrees of liver fibrosis in a majority of those infected, and causes cirrhosis in 20 to 30 percent. This damage is classified in five stages of increasing severity, from zero to four. Using sofosbuvir-ledipasvir, which is sold as Harvoni, and is one several new drugs for hepatitis C, researchers compared the costs of treating patients at all stages of fibrosis, zero through four, with the cost of waiting until stages three or four, which is when some patients are usually treated.

They found that, at current drug prices, treating half of those who are currently infected and are aware of their status but have not yet been treated would cost about $53 billion over five years, while treating these patients only at stages three and four would cost $30 billion. Since many of those patients are likely to be given the drugs at later stages of their disease, much of this cost is likely unavoidable, even if it gets delayed. But treating people early would at least avoid the costs of treating the damage from long-term infection. Researchers estimated the lifetime health care savings from treating all stages of liver fibrosis, compared to treating just three and four, at $3.3 billion.

"The budgetary implications of widespread treatment are quite large at current drug prices," said James G. Kahn, MD, MPH, a professor in the UCSF department of epidemiology and biostatics, as well as medicine. "However, these costs are time-limited, and they are lower than some other treatments that are less effective. In the U.S., we spend more than $140 billion a year treating cancer, often with less health benefit than is provided by the new hepatitis C treatments."

The researchers said it was important to broaden the discussion beyond cost-effectiveness, to include the price of drugs.

"The benefits of early therapy are significant, since it increases the number of healthy life years for patients and decreases their chances of getting serious liver diseases, like liver failure and liver cancer," said Harinder Chahal, PharmD, MSc, an assistant adjunct professor in the UCSF department of clinical pharmacy. "But the current prices are keeping early treatment out of reach for many patients, and this needs to be addressed."

###

Other authors include Rena Fox, MD, and Jeffrey Tice, MD, of UCSF; Elliot Marseille, PhD, of Health Strategies International; and Daniel Ollendorf, PhD, and Steve Pearson, MD, MSc, of the Institute for Clinical and Economic Review in Boston.

The study was supported by the Blue Shield of California Foundation, the California Health Care Foundation, the UCSF Clinical and Translational Sciences Institute and the National Institute on Drug Abuse.

UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy, a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences, as well as a preeminent biomedical research enterprise and two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children's Hospital San Francisco. Please visit http://www.ucsf.edu.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Platelets promote the liver's regeneration process following surgery

Platelets promote the liver's regeneration process following surgery

(Vienna, 23 November 2015) A team of researchers at the MedUni Vienna has discovered that certain platelet-derived growth factors are of major significance for the liver's regeneration processes. It has been shown that platelets can encourage the regrowth of liver tissue in patients who have had parts of their liver removed surgically. This may also act as a starting point for the prediction of potential post-operative problems. The work has been published in the key journal on liver medicine, "Hepatology".

Platelets are a vital part of wound healing processes. They can specifically secrete key growth factors at the site of the injury and therefore start the damaged tissue's regeneration processes. In the latest study, which involved collaboration between the University Department of Surgery at the MedUni Vienna led by Patrick Starlinger and the Institute of Physiology led by Alice Assinger, scientists were able to demonstrate that the specific release of growth factors from the α granules was associated with post-operative liver regeneration.

The authors of this study demonstrated back in 2014 that serotonin stored in platelets can play a key role in post-operative liver regeneration. Serotonin is stored in the electron-dense granules (storage organelles) of platelets and is secreted after activation. As part of the platelet activation process, the contents of a second type of granule, known as the α granule, are also released. It has now been possible for the first time to prove a highly selective release of α granules in vivo and demonstrate the resulting pathophysiological consequences.

These granules contain both growth-promoting and growth-inhibiting factors. In vitro data from previous years have shown that platelets can be present not just, as was previously thought, in an activated or non-activated state, but instead that they are able, depending on the underlying stimulus, to release growth-promoting or growth-inhibiting factors on a highly specific basis. In the past, it was not known whether this mechanism also has a role to play in vivo and therefore has pathophysiological consequences.

The liver is the only organ that is able to regenerate itself, even after extensive damage or after parts of it have been surgically removed (resected). Up to 75 per cent of the liver tissue can be removed without the organ's metabolic functions being permanently impaired.

The liver's tremendous potential for regeneration and advancing developments in the field of liver surgery mean that even patients with impaired liver function are able to undergo intricate resections. However, impairment of liver function still occurs in a certain percentage of patients following surgery. This liver impairment can develop into life-threatening complications and is associated with a relatively high degree of mortality. The exact causes of liver failure are so far not fully understood.

Hepatic vein blood pressure could determine selective α granule release
The scientists have now also been able to show that there is a relationship between platelet-derived growth factors and hepatic vein blood pressure. Pre-existing liver disease, which causes changes to the blood pressure in the hepatic vein, is regarded as a risk factor for post-operative complications. "We were able to demonstrate that, in patients with high hepatic vein blood pressure, the release of growth-promoting substances is suppressed and increased levels of growth-inhibiting factors are released. These findings will help us to better understand the dangerous consequences of changes in hepatic vein blood pressure," explains Starlinger. The findings obtained from the study could make a major contribution towards the development of new treatment strategies aimed at ensuring improved liver regeneration following liver resection surgery and therefore also reducing the risk of liver failure that has to date been untreatable.

Service: Hepatology
The Profile of Platelet α-Granule Released Molecules Affects Postoperative Liver Regeneration. Starlinger P, Haegele S, Offensperger F, Oehlberger L, Pereyra D, Kral JB, Schrottmaier WC, Badrnya S, Reiberger T, Ferlitsch A, Stift J, Luf F, Brostjan C, Gruenberger T, Assinger A. 2015 Nov 3. doi: 10.1002/hep.28331http://www.ncbi.nlm.nih.gov/pubmed/26528955

Five research clusters at the MedUni Vienna
There are a total of five research clusters at the MedUni Vienna. The MedUni Vienna is increasingly focusing on fundamental and clinical research in these areas. The research clusters include medical imaging, cancer research / oncology, cardiovascular medicine, medical neurosciences and immunology. Surgical and hepatology research at the MedUni Vienna falls under the remit of the immunology cluster.

Source

Daklinza(Daclatasvir): Bristol-Myers Lets Low-Income Countries Copy Hepatitis C Pills

Bristol-Myers Lets Low-Income Countries Copy Hepatitis C Pills
Caroline Chen

Bristol-Myers Squibb Co. has signed a broad agreement with Medicines Patent Pool, allowing the United Nations-backed organization to distribute licenses for generic-drug companies to copy its hepatitis C treatment in more than 100 developing and middle-income nations.

The agreement allows the generics makers to produce copies of the drug Daklinza, known chemically as daclatasvir, without paying any royalties, Medicines Patent Pool said in a statement Monday. The liver ailment is a new treatment area for the organization, which has helped developing nations gain access to HIV medicines.

Continue reading.... 

Bristol-Myers signs deal with UN group for generic hep C drug
Source: Reuters - Mon, 23 Nov 2015 14:19 GMT

Nov 23 (Reuters) - A United Nations-backed organization working to cut the price of HIV drugs said it had signed a deal with Bristol-Myers Squibb Co to allow generic versions of the company's hepatitis C drug to be sold in 112 low- and middle-income countries.

The drug, Daklinza, is on the World Health Organization's list of essential medicines.

Hepatitis C affects about 150 million people globally and kills around half a million each year, the World Health Organisation estimates.

The Medicines Patent Pool said on Monday that Daklinza would now be available to nearly two-thirds of people affected by the disease in low- and middle-income countries.

The list price in the United States for Daklinza is $63,000 for a 12-week regimen, or about $750 per day at wholesale costs, according to pharmacy benefits manager Express Scripts.

Other drugs used to treat hepatitis C include Gilead Sciences' Sovaldi. A single Sovaldi pill costs $1,000 in the United States, according to Express Scripts.

The deal with Bristol-Myers allows drugmakers anywhere in the world to develop generic versions of Daklinza.

The Medicines Patent Pool had earlier signed a deal with Bristol-Myers for generic versions of its HIV treatment Reyataz. (Reporting by Vidya L Nathan in Bengaluru; Editing by Ted Kerr)

Reuters

Exclusive HCV Interview: Lucinda K Porter, RN

Exclusive HCV Interview: Lucinda K Porter, RN
Posted on November 14, 2015

Please tell me a little bit about yourself.
LUCINDA: I was a patient who was infected with hepatitis C in 1988, and I turned that into an opportunity to learn more about hepatitis C. I have been working in this field since 1997. Along the way, I worked at Stanford Medical Center in their Hepatology Division. I’ve also done a lot of writing since the late ’90s, and I wrote two books, both of them on hepatitis C. Currently, I work as a contributing editor for HepMag.com and write for the HCV Advocate. My bio is on my website (http://www.lucindaporterrn.com).

My first question is what do you see as the biggest challenges associated with the hepatitis C epidemic in the U.S.?
LUCINDA: I see three problems. The first is that we need to identify and test those patients who are still undiagnosed. I think that’s a huge issue because they’re not getting screened, particularly baby boomers.

Number two is once they’re screened, we need linkage to care and access to treatment. Many patients are facing huge hurdles trying to access treatment. There are some unscientific, unmedically-based reasons why insurance payers and state Medicaid programs are denying hepatitis C treatment to patients.

The third problem is that we need to do something about the current increase in new infections, particularly in high risk communities such as Kentucky, West Virginia, Tennessee, and Indiana, as well as in other areas of the U.S. that are having problems with opioid addiction, whether from prescription painkillers or heroin. New hepatitis C and HIV infections are on the rise, and the tragic fact is that there are multiple ways we could prevent these.

Between 2010 and 2013, there was a 150 percent increase in new infections. Twelve states reported a 200 percent increase in new hepatitis C infections in the past few years. It’s really a problem.

Continue reading....

Galectin Therapeutics - Developing New Treatments For Fibrosis and Cirrhosis

Q&A With Peter Traber From Galectin Therapeutics: Developing New Treatments For Fibrosis and Cirrhosis

Conference Coverage > AASLD 2015

Nov 20, 2015 | Adam Hochron

In the effort to help the growing number of people with liver disease new medications are constantly being developed. This is true for a wide range of conditions including cirrhosis and fibrosis.

While not presenting any new data at this year's Liver Meeting in San Francisco Galectin Therapeutics CEO Peter Traber, MD, discussed work being done in this field which could provide much needed treatment for these patients in the near future.

ASTRAL-2: Sovaldi/velpatasvir bests standard therapy in HCV genotype 2

Healio: Additional headlines from Highlights from The Liver Meeting 2015

ASTRAL-2: Sovaldi/velpatasvir bests standard therapy in HCV genotype 2
SAN FRANCISCO — A fixed-dose combination of Sovaldi and velpatasvir yielded better sustained virologic response rates in patients with genotype 2 hepatitis C virus than Sovaldi and ribavirin, the current standard of care, according to findings presented at The Liver Meeting 2015.
Mark S. Sulkowski, MD, of Johns Hopkins University, noted that there is currently no ribavirin-free regimen approved for the treatment of this patient population. The open-label study had broad inclusion criteria, allowing for patients with treatment experience and cirrhosis, and was conducted at 51 centers in the U.S.

Continue reading....

ASTRAL-1: Sovaldi/velpatasvir shows pangenotypic activity

November 17, 2015
SAN FRANCISCO — A fixed-dose combination of Sovaldi and velpatasvir yielded 99% SVR12 across a number of genotypes, according to a presentation…

Sovaldi, velpatasvir, GS-9857 show efficacy in challenging populations
November 17, 2015
SAN FRANCISCO — A cohort including patients with genotype 3 disease demonstrated high SVR12 rates after treatment with Sovaldi, velpatasvir (or…

New England Journal Of Medicine 

Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection
Here, we present the results of two randomized, controlled, phase 3 trials (ASTRAL-2 and ASTRAL-3) in which treatment with a fixed-dose combination tablet of sofosbuvir and velpatasvir for 12 weeks was compared with standard treatment with sofosbuvir plus ribavirin for 12 or 24 weeks in patients who had received prior treatment for HCV genotype 2 or 3 infection and in those who had not received such treatment, including those with compensated cirrhosis.

Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis
The NS5B nucleotide inhibitor sofosbuvir is approved for the treatment of HCV infection in combination with other agents.13,14 Velpatasvir (formerly known as GS-5816, Gilead Sciences) is an investigational inhibitor of the HCV NS5A protein with antiviral activity against all HCV genotypes.15-17 The combination of velpatasvir and sofosbuvir with or without ribavirin provided high rates of sustained virologic response in patients with all HCV genotypes in phase 2 clinical trials.18,19 In the phase 3 ASTRAL-1, ASTRAL-2, and ASTRAL-3 trials (now published in theJournal),20,21 treatment with sofosbuvir–velpatasvir in a fixed-dose combination tablet for 12 weeks resulted in high rates of sustained virologic response among patients with HCV genotypes 1 through 6 without cirrhosis or with compensated cirrhosis.

Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection
We conducted a phase 3 trial (ASTRAL-1) to assess the efficacy and safety of 12 weeks of treatment with a fixed-dose combination of velpatasvir and sofosbuvir among both previously treated and untreated patients who were chronically infected with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis.

Slide presentation with full text @ NATAP

Sofosbuvir Plus Velpatasvir (GS-5816) Combination Therapy for Treatment-Experienced Patients With Genotype 1 or 3 Hepatitis C Virus Infection: A Randomized Trial 

Sofosbuvir/Velpatasvir + GS-9857 for 6 or 8 Weeks in Genotype 1 or 3 HCV-Infected Patients 

Watch Patients Treated For Hepatitis C: Studying possible regression in cirrhosis/ fibrosis

Q&A With Ana Maria Crissien From Scripps Green Hospital: Studying Regression In Liver Disease
Conference Coverage > AASLD 2015

Nov 19, 2015 | Adam Hochron
A considerable amount of research has been done looking at how liver disease can progress in patients, but a recent study looked at possible regression in conditions like cirrhosis and fibrosis. Ana Maria Crissien, MD, from the Scripps Green Hospital in California discussed the results of this research during the annual Liver Meeting in San Francisco.

2015 Liver Meeting | AASLD 2015

Q&A with Barry Schlansky, MD, from Oregon Health & Science University: Taking a New Look at Liver Transplants for Obese Patients VIDEO
Nov 18, 2015 | AASLD 2015 | Adam Hochron
In the past, patients deemed obese (especially those who were morbidly obese) may have been passed over for a life-saving liver transplant. A recent study showed they may be just as viable candidates for the procedure as others in the patient population.

Should Obese Patients Get Liver Transplants?
Nov 18, 2015 | AASLD 2015 | Gale Scott
Obese people are generally less healthy than those of normal weight, but that should not be a barrier to liver transplantation, researchers said at the 2015 Liver Meeting (AASLD) in San Francisco, CA.

Nations Awaiting Price Break in HCV Drugs
Nov 18, 2015 | AASLD 2015 | Gale Scott
Price is still the main obstacle in getting hepatitis C direct-acting antivirals to nations that need them, panelists agreed at a "global challenges" forum at the 2015 Liver Meeting in San Francisco, CA.

Who Gets a Liver? Transplant Centers Differ on Substance Abuse Abstinence Rules
Nov 17, 2015 | AASLD 2015 | Gale Scott
Donor livers are scarce, donated organs are precious, and transplant surgeons make the final call on whether to transplant. When the question of whether to give a liver to a patient who uses marijuana, drinks too much alcohol, or even smokes tobacco comes up, the issue gets tricky.

HCV: Making it Rare in the US Will Cost $106 Billion, Study Finds
Nov 17, 2015 | AASLD 2015 | Gale Scott
The annual US cost of HCV treatment before direct-acting antivirals was $7 billion and since then it has grown to $21 billion, but that cost should drop when generics arrive, to $14 million annually by 2030. Making it a rare disease over the next 25 years will take $106 billion, researchers project.

Vitamin E Looks Promising, Safe, for Liver Disease
Nov 17, 2015 | AASLD 2015 | Gale Scott
Researchers see promise in vitamin E treatment for NASH.

Coverage starts here.....

Watch Independent Expert Review on AASLD 2015: Discussion on HCV therapeutic options and developments

Replay from 11/16 Available! - CME Satellite Symposium

11/16/15 - San Francisco, CA

CLICK HERE TO VIEW THE PROGRAM

HCV in 2015 - The CME Internet Symposium: AASLD 2015 Expert Review will feature four HCV experts reviewing and discussing key presentations on chronic hepatitis C presented at AASLD 2015. 

The review and discussion will focus on HCV therapeutic options and developments, including: current treatment and management strategies, algorithms and recommendations; therapies in development; epidemiology; and diagnosis and clinical management of specific patient populations, including HCV/HIV co-infected and cirrhotic patients.

This activity will enable participating health care providers caring for HCV-infected patients to become aware of and understand the data presented at this important conference and appropriately utilize those data to improve patient care. All online components of the program can be accessed at www.viraled.com

This program is produced by the Postgraduate Institute for Medicine and ViralEd, Inc. It is not a session created by or presented at AASLD 2015 and it is not sanctioned by the organizers of AASLD 2015.

US calls for a ban on advertising prescription drugs

US calls for a ban on advertising prescription drugs

BY SUSAN KELLY

The American Medical Association on Tuesday called for a ban on advertising prescription drugs and medical devices directly to consumers, saying the ads drive patients to demand expensive treatments over less costly ones that are also effective.

The influential doctors' group said the new policy reflects physicians' concerns that marketing spending on a proliferation of advertising is helping to drive up drug prices. The group voted at its annual meeting in Atlanta to support a ban.

"Direct-to-consumer advertising also inflates demand for new and more expensive drugs, even when those drugs may not be appropriate," AMA Board Chair-elect Patrice Harris said in a statement.

The United States and New Zealand are the only two countries that allow direct-to-consumer advertising of prescription drugs.

AMA said drugmakers' spending on advertising has shot up 30 percent in the last two years to $4.5 billion. TV commercials for drugs such as Bristol-Myers Squibb's lung cancer medicine Opdivo and Gilead Sciences' Hepatitis C treatment Harvoni were among this year's ad campaigns.

US Democratic presidential candidate Hillary Clinton has proposed cracking down on direct-to-consumer advertising and other measures to stop what she called "price gouging" by pharmaceutical companies. Clinton's plan would prevent companies from deducting what they spend on direct-to-consumer ads from their tax bills.

A series of court decisions has determined the ads cannot be banned outright because they are a form of commercial speech protected by the US Constitution. The AMA did not address how the ban could be accomplished without being overturned in court.

PhRMA, the largest US trade group for the pharmaceutical industry, said the ads increase consumer awareness of available treatments for diseases, including undiagnosed conditions.

"Providing scientifically accurate information to patients so that they are better informed about their health care and treatment options is the goal of direct-to-consumer pharmow said in an email.

According to a US Food and Drug Administration analysis this year, 52 percent of Americans believe direct-to-consumer ads do not have enough information about risks and 46 percent say the ads aceutical advertising about prescription medicines," PhRMA spokesman Tina Stlack information about benefits.

http://www.reuters.com/article/2015/11/17/us-pharmaceuticals-advertising-idUSKCN0T62WT20151117#6SFFdTwWfHwemQBq.97

AASLD 2015 - The Risk of Developing Liver Cancer Even After Being Cured from Hepatitis C

The Risk of Developing Liver Cancer Even After Being Cured from Hepatitis C

SAN FRANCISCO, Nov. 15, 2015 /PRNewswire/ -- Hepatocellular carcinoma (HCC) remains one of the cancers growing in frequency and mortality in the United States. Patients with hepatitis C virus (HCV) left untreated will often progress to cirrhosis and HCC. Direct acting antivirals (DAAs) now used to treat patients with HCV have achieved almost universal cure rates. However, the risk of HCC following cure is not clear. Researchers from Houston VA Medical Center and Baylor College of Medicine (Houston, TX) presented data at the annual meeting of the American Association for the Study of Liver Diseases on the risk of developing HCC in patients with HCV who have achieved sustained virologic response (SVR).

This retrospective national cohort study examined the records of patients who achieved SVR using interferon-based therapy and who had at least one year of follow up in the national VA system. There were 10,738 patients who achieved SVR and had no HCC prior to SVR. Of those patients who achieved SVR, 100 developed HCC after SVR.

Dr. El-Serag, the study's principal investigator, concluded that the risk of developing HCC after being cured of HCC remains elevated with an overall incidence of 0.33 percent per year. Being older, or having cirrhosis at the time of SVR were associated with annual HCC risk of 0.9% and 1.55%, respectively. Diabetes and previous genotype 3 were also associated with an additional increased risk of developing HCC after HCV cure. Dr. El-Serag addresses those at an increased risk of developing HCC, "Subgroups such as age 65 years and older, those with diabetes and especially those with cirrhosis have even higher rates -- closer to or higher than 1 percent per year -- of developing HCC."

"The results pertain to mostly male veterans treated with interferon-based treatments and therefore may not be generalizable to women, nonveterans and those cured using DAA," cautioned Dr. El-Serag. He added, "We still need to examine large cohorts of DAA-cured patients, and examine several demographic, clinical, and genetic factors that may serve as predictor or prognostic markers.

When asked to address the overall significance of this study, Dr. El-Serag replied, "We will be facing large numbers of cured HCV patients and this study gives us a glimpse what the clinical course might be. It is clear that while cure considerably reduces HCC risk in general, it does not eliminate it especially when cirrhosis is present and in those who get cured at an old age. Therefore, the sooner we cure patients the better off we are. Furthermore continued vigilance and HCC surveillance is warranted after cure in these subgroups."

Abstract title: Incidence and predictors of hepatocellular carcinoma following sustained virological response: A national cohort study

AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in San Francisco, CA, November 14-17, will bring together more than 9,000 researchers from 55 countries.

A pressroom will be available from November 13 at the annual meeting. For copies of abstracts and press releases, or to arrange researcher interviews, contact Gregory Bologna at 703-299-9766.

Press releases and all abstracts are available online at www.aasld.org.

/PRNewswire

NEJM EDITORIAL: Simple, Effective, but Out of Reach? Public Health Implications of HCV Drugs

EDITORIAL 

New England Journal Of Medicine 

Simple, Effective, but Out of Reach? Public Health Implications of HCV Drugs

John W. Ward, M.D., and Jonathan H. Mermin, M.D., M.P.H.
November 17, 2015

DOI: 10.1056/NEJMe1513245

The results of four clinical trials showing the excellent safety and efficacy of a 12-week course of sofosbuvir (an NS5B inhibitor licensed in the United States in 2013) and velpatasvir (a new NS5A inhibitor) in treating patients with hepatitis C infection (HCV) are reported now in the Journal.1-3 In two of these studies, ASTRAL-1 and ASTRAL-2, 97 to 100% of patients with HCV genotype 1a, 1b, 2, 4, 5, or 6 had a sustained virologic response at 12 weeks after the end of therapy, a marker that is indicative of virologic cure. Similar efficacy was observed among patients in whom previous treatment had failed and those with compensated cirrhosis, factors that have been associated with a reduced response to the treatment of HCV infection.4

Continue reading @ NEJM

Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection

We conducted a phase 3 trial (ASTRAL-1) to assess the efficacy and safety of 12 weeks of treatment with a fixed-dose combination of velpatasvir and sofosbuvir among both previously treated and untreated patients who were chronically infected with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis.

Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection

Here, we present the results of two randomized, controlled, phase 3 trials (ASTRAL-2 and ASTRAL-3) in which treatment with a fixed-dose combination tablet of sofosbuvir and velpatasvir for 12 weeks was compared with standard treatment with sofosbuvir plus ribavirin for 12 or 24 weeks in patients who had received prior treatment for HCV genotype 2 or 3 infection and in those who had not received such treatment, including those with compensated cirrhosis.

Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis

The number of patients with decompensated cirrhosis caused by chronic infection with the hepatitis C virus (HCV) is projected to rise in the coming decade.1 For many years, the only treatment option for such patients was liver transplantation. Recently, however, clinical trials of newly approved direct-acting antiviral agents have shown that it is possible to treat HCV infection safely and effectively in patients with decompensated cirrhosis and that successful treatment is associated with early improvement in liver function.2-11 The possible long-term benefits of treatment on existing liver disease remain unknown. The only regimen that is currently approved for the treatment of HCV infection in patients with decompensated cirrhosis is 24 weeks of ledipasvir–sofosbuvir plus ribavirin, which is approved in Europe for patients with HCV genotypes 1 and 4.12 A highly effective regimen to treat HCV infection of all genotypes in patients with decompensated liver disease that has acceptable side effects would address a significant unmet medical need.

The NS5B nucleotide inhibitor sofosbuvir is approved for the treatment of HCV infection in combination with other agents.13,14 Velpatasvir (formerly known as GS-5816, Gilead Sciences) is an investigational inhibitor of the HCV NS5A protein with antiviral activity against all HCV genotypes.15-17 The combination of velpatasvir and sofosbuvir with or without ribavirin provided high rates of sustained virologic response in patients with all HCV genotypes in phase 2 clinical trials.18,19 In the phase 3 ASTRAL-1, ASTRAL-2, and ASTRAL-3 trials (now published in theJournal),20,21 treatment with sofosbuvir–velpatasvir in a fixed-dose combination tablet for 12 weeks resulted in high rates of sustained virologic response among patients with HCV genotypes 1 through 6 without cirrhosis or with compensated cirrhosis.

We conducted a phase 3, open-label trial to assess the efficacy and safety of a fixed dose of sofosbuvir–velpatasvir with or without ribavirin for 12 weeks or sofosbuvir–velpatasvir for 24 weeks in patients infected with HCV genotypes 1 through 6 and with decompensated cirrhosis...

Continue reading...

AASLD Coverage @ Healio 
ASTRAL-1: Sofosbuvir/velpatasvir shows pangenotypic activity
SAN FRANCISCO — A fixed-dose combination of Sovaldi and velpatasvir yielded 99% SVR12 across a number of genotypes, according to a presentation at the Late Breakers session of The Liver Meeting 2015.

“Although there has been phenomenal progress in HCV therapy over the last few years, interferon-free regimens are not pangenotypic and, therefore, most regimens need to be selected for specific patient groups,” Jordan J. Feld, MD, of the Toronto Western Hospital Liver Centre, said in his presentation.

Continue reading..

AASLD Late-Breaking Abstract Session

Monday, November 16, 2:45 pm - 4:30 pm
LB-2 A Phase 3 Double-Blind Placebo-Controlled Evaluation of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Naïve and Experienced Genotype 1, 2, 4, 5, 6 HCV Infected Patients with and without cirrhosis: Results of the ASTRAL-1 Study

Simple drug regimen cures hepatitis C virus in patients after 12 weeks

November 16, 2015

Source:University Health Network (UHN)

Summary:Researchers have found that a simple drug regimen delivered over 12 weeks achieved sustained eradication of several genotypes of the hepatitis C virus (HCV) in 99 per cent of the trial's patients.

Chronic HCV is known as a "silent" killer because symptoms often don't appear until the liver is severely damaged. Left undiagnosed, HCV can lead to cirrhosis which can progress to liver failure or liver cancer. HCV is primarily spread by blood-to-blood contact and is associated with intravenous drug use, contact with poorly sterilized medical equipment and blood transfusions before 1992.

Researchers at the Toronto Western Hospital (TWH) Liver Clinic have found that a simple drug regimen delivered over 1​2 weeks achieved sustained eradication of several genotypes of the hepatitis C virus (HCV) in 99 per cent of the trial's patients.

The study, released in the New England Journal of Medicine, showed that receiving a once daily drug combination of sofosbuvir-velpatasvir for a 12 week period was effective in both treatment-naïve and previously treated patients with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis (where scarring of the liver has occurred but patients have yet to experience symptoms as a result of it).

"This drug regimen changes the standard of care in treating patients with HCV -- we can now cure almost everyone with a very simple treatment," said Dr. Jordan Feld, Hepatologist, Francis Family Liver Clinic, TWH and the first author of the study. "It's incredibly gratifying to be part of research where we not only cure a disease but can also think about eliminating HCV in Canada."

Current approved treatments for chronic HCV are not equally effective in combating the virus' different genotypes. Testing to determine the genotype and subtype of the virus is required before treatment could be initiated. But the combination of sofosbuvir-velpatasvir has been shown to be applicable to all strains of HCV, effectively eliminating the need to test for the viral genotype -- an obstacle that often delayed treatment.

The regimen was tested in an international, randomized, double-blind placebo-controlled phase three trial conducted at 81 sites in eight different countries. After 12 weeks, 99 per cent of the 624 patients who had been treated with a daily tablet of sofosbuvir-velpatasvir experienced a sustained virologic response -- the medical term for eradication or cure of HCV -- meaning that patients remained free of the virus three months after completing treatment. None of the 116 patients receiving a placebo experienced the same result.

"This is truly a one size fits all treatment that is very easy to administer and extremely well tolerated," said Dr. Feld. "Our challenge now is getting treatment to those who need it. Over half of people living with hepatitis C remain undiagnosed. Fortunately this regimen, along with other advances in therapy, will allow us to move treatment out of specialty clinics so that we can deliver care and ideally cure all infected Canadians."

Chronic HCV is known as a "silent" killer because symptoms often don't appear until the liver is severely damaged. Left undiagnosed, HCV can lead to cirrhosis which can progress to liver failure or liver cancer. HCV is primarily spread by blood-to-blood contact and is associated with intravenous drug use, contact with poorly sterilized medical equipment and blood transfusions before 1992.

Approximately 170 million people are infected with chronic HCV worldwide with an estimated 252,000 in Canada. HCV causes the greatest burden of disease, measured in years of life lost, than any infectious disease in Canada.​

Story Source:
The above post is reprinted from materials provided by University Health Network (UHN). Note: Materials may be edited for content and length.

Journal Reference:
Jordan J. Feld, Ira M. Jacobson, Christophe Hézode, Tarik Asselah, Peter J. Ruane, Norbert Gruener, Armand Abergel, Alessandra Mangia, Ching-Lung Lai, Henry L.Y. Chan, Francesco Mazzotta, Christophe Moreno, Eric Yoshida, Stephen D. Shafran, William J. Towner, Tram T. Tran, John McNally, Anu Osinusi, Evguenia Svarovskaia, Yanni Zhu, Diana M. Brainard, John G. McHutchison, Kosh Agarwal, Stefan Zeuzem.Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. New England Journal of Medicine, 2015; 151116141724000 

DOI: 10.1056/NEJMoa1512610

Liver Disease A Serious Concern in Veteran Population

Q&A With Lauren Beste From VA Puget Sound Health Care System: Liver Disease A Serious Concern in Veteran Population

Conference Coverage > AASLD 2015

Nov 16, 2015 | Adam Hochron

With an aging veteran population there are a number of conditions that need to be treated in these patients as well as others of their generation, particularly in when it comes to liver disease. Lauren Beste, MD, MSc, from the VA Puget Sound Health Care System in Seattle discussed a recent study looking at how conditions like cirrhosis and hepatocellular carcinoma are treated and the prevalence of these conditions in the veteran population during the recent Liver Meeting in San Francisco.

Source 

AASLD Coverage 

Q&A With Melissa Harris From Bristol-Myers Squibb: Expanding Hepatitis C Treatment To New Genotypes And Populations VIDEO
Nov 16, 2015 | AASLD 2015 | Adam Hochron
Hepatitis C is becoming a more commonly treated condition in many of its genotypes while others continue to present problems for the pharmaceutical and medical communities. Work is being done to overcome those challenges around the world.

Alcoholic Hepatitis: Filtering Device Helped Younger, Less Ill Patients
Nov 14, 2015 | AASLD 2015 | Gale Scott
A human-cell-based liver support system meant to keep patients alive despite acute liver failure did not help overall survival in a trial, but showed promise for a subset of patients. Those patients were younger and not as sick—though all subjects enrolled had alcoholic hepatitis.

Hepatitis C: Looking for an Effective Regimen for Genotype 3
Nov 14, 2015 | AASLD 2015 | Gale Scott
Hepatitis C genotype 3 can be hard to cure, but researchers presenting a study at the Liver Meeting (AASLD) in San Francisco, CA, said they have found a regimen that works.

HCV in Egypt: Success in Treating Genotype 4
Nov 14, 2015 | AASLD 2015 | Gale Scott
Egypt has the highest prevalence of hepatitis C in the word and most of it (90%) is genotype 4. Researchers presenting a study at the Liver Meeting (AASLD) in San Francisco, CA, reported success in a trial of ravidasvir

Insurance Lagging on Paying for HCV Antivirals
Nov 14, 2015 | AASLD 2015 | Gale Scott
The high costs of direct-acting antivirals to treat hepatitis C infection is no secret, but neither is the fact that the drugs are cost-effective. Pennsylvania researchers found insurers were lagging in approving payment for the drugs in their four-state region, with Medicaid programs the worst offenders.

HCV Antiviral Resistance a Challenge
Nov 14, 2015 | AASLD 2015 | Gale Scott
Despite the success of direct antivirals in curing hepatitis C, there are concerns about resistance to the drugs.

ABBVIE Announces High SVR In Phase 2 studies With Pan-Genotypic Investigational Regimen ABT-493 AND ABT-530

ABBVIE ANNOUNCES HIGH SUSTAINED VIROLOGIC RESPONSE RATES IN PHASE 2 STUDIES WITH PAN-GENOTYPIC, INVESTIGATIONAL REGIMEN IN PATIENTS WITH CHRONIC HEPATITIS C

- INVESTIGATIONAL HCV REGIMEN WITH ABT-493 AND ABT-530 EVALUATING A PAN-GENOTYPIC, ONCE-DAILY TREATMENT OPTION WITH SHORTER DURATION OF THERAPY

- LATE-BREAKING DATA DEMONSTRATE 97 PERCENT SVR(12) IN GENOTYPE 1 NON-CIRRHOTIC CHRONIC HEPATITIS C PATIENTS AFTER 8 WEEKS OF TREATMENT WITH ABT-493 AND ABT-530

- FIRST PATIENT ENROLLED IN PHASE 3 TRIALS

Nov 16, 2015

NORTH CHICAGO, Ill., Nov. 16, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced data from the SURVEYOR studies of its investigational HCV regimen, ABT-493, an NS3/4A protease inhibitor, and ABT-530, an NS5A inhibitor, that show high rates of sustained virologic response at 12 weeks post-treatment (SVR₁₂) in non-cirrhotic patients with chronic hepatitis C virus (HCV) infection. After 12 weeks of treatment, SVR₁₂ rates achieved were 97-100 percent in genotype 1 (GT1), 96-100 percent in genotype 2 (GT2) and 83-94 percent in genotype 3 (GT3) patients.^1,2,3 These data are being presented at The Liver Meeting^® 2015, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco.

Separately, in a late-breaking presentation of the SURVEYOR-I study, data show non-cirrhotic GT1 chronic HCV patients who received a shorter duration of treatment for 8 weeks with ABT-493 and ABT-530 achieved a SVR₁₂ rate of 97 percent.⁴

"These results are encouraging and contribute to scientific knowledge about the potential for pan-genotypic options for treating chronic hepatitis C," said Fred Poordad, M.D., vice president of Academic and Clinical Affairs at The Texas Liver Institute in San Antonio. "These data mark another important step in the continued research to help address the unmet needs of patients and the medical community."

SURVEYOR-I and SURVEYOR-II are ongoing Phase 2 clinical studies that evaluate the safety and efficacy of ABT-493 and ABT-530, with or without ribavirin (RBV), for 8 to 12 weeks. These data presented at AASLD include non-cirrhotic patients with GT1, GT2 and GT3 chronic HCV infection. Data in additional patient populations (genotypes 4-6) will be presented at future meetings.

"The SURVEYOR trials offer important new information about the potential to treat patients with chronic hepatitis C across multiple genotypes with our two direct-acting antiviral investigational regimen," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "AbbVie's ongoing hepatitis C research program demonstrates our commitment to make a remarkable impact on the lives of HCV patients."

About SURVEYOR-I  SURVEYOR-I is an ongoing Phase 2 two-part study designed to evaluate the safety and efficacy of ABT-493 and ABT-530, with and without ribavirin (RBV), for 8 to 12 weeks, in cirrhotic and non-cirrhotic adult genotype 1 (GT1) patients, and non-cirrhotic adult patients with genotypes 4, 5 or 6 chronic HCV infection who were new to therapy or did not respond to previous treatment with pegylated interferon (pegIFN)/RBV (null responder).^1,4

In Part 1 of SURVEYOR-I, with 12 weeks of treatment, no patients discontinued treatment due to severe adverse events. The most commonly-reported direct-acting antiviral related adverse reactions (>10 percent of patients) were fatigue, headache and nausea. One patient experienced a serious adverse event of metastatic prostate cancer, unrelated to the study drugs and had onset after completion of study treatment.¹ In Part 2, with 8 weeks of treatment, there were no study-related serious or severe adverse events reported. One subject discontinued the study at treatment week 4 due to adenocarcinoma, unrelated to study drugs. The most frequent adverse event (>10 percent of patients) was fatigue.⁴

About SURVEYOR-II  SURVEYOR-II is an ongoing Phase 2 three-part study designed to evaluate the safety and efficacy of ABT-493 and ABT-530, with or without ribavirin (RBV), in cirrhotic and non-cirrhotic adult patients with genotype 2 (GT2) or genotype 3 (GT3) chronic HCV infection who were new to therapy or had failed previous treatment with pegIFN/RBV.^2,3 In GT2 study patients, the most commonly-reported direct-acting antiviral (DAA)-related adverse reactions (>10 percent of patients) were fatigue, nausea, diarrhea and headache. No GT2 study patients discontinued treatment due to an adverse event; one patient experienced a serious adverse event of atrial fibrillation unrelated to the study drugs.² In GT3 study patients, the most commonly-reported DAA-related adverse reactions (>10 percent of patients) were fatigue, nausea and headache. One patient discontinued treatment due to DAA- and RBV-related adverse events of abdominal pain and heat sensation. Two patients experienced a serious adverse event, one with pneumonia and one with B-cell lymphoma, both unrelated to the study drugs.³  Part 1 results of the SURVEYOR-II are presented at AASLD.

Overview of SURVEYOR-I and SURVEYOR-II Clinical Data Presented at AASLD:

SURVEYOR-I (Genotype 1, Non-cirrhotic)
Number of Patients (n)/ Patient Population	Duration of Treatment	Treatment Arm	Treatment Regimen	SVR12Rates
n=40 Treatment-naïve=63% pegIFN/RBV null responders=37%	12 weeks	Arm A	ABT-493 (200mg) + ABT-530 (120mg) once daily	100% (n=40/40)
n=39 Treatment-naïve=64% pegIFN/RBV null responders=36%		Arm B	ABT-493 (200mg) + ABT-530 (40mg) once daily	97% (n=38/39)
n=34 Treatment-naïve=85% pegIFN/RBV treatment experienced=15%	8 weeks	Arm K	ABT-493 (300mg) + ABT-530 (120mg) once daily	97% (n=33/34)
SURVEYOR-II (Genotype 2, Non-cirrhotic)
Number of Patients (n)/ Patient Population	Duration of Treatment	Treatment Arm	Treatment Regimen	SVR12Rates
n=74 Treatment-naïve=88% pegIFN/RBV treatment experienced=12%	12 weeks	Arm A	ABT-493 (300mg) + ABT-530 (120mg) once daily	96% (n=24/25)
		Arm B	ABT-493 (200mg) + ABT-530 (120mg) once daily	100% (n=24/24)
		Arm C	ABT-493 (200mg) + ABT-530 (120mg) once daily + RBV (weight-based, 1000 or 1200mg) twice daily	100% (n=25/25)
SURVEYOR-II (Genotype 3, Non-cirrhotic)
Number of Patients (n)/ Patient Population	Duration of Treatment	Treatment Arm	Treatment Regimen	SVR12Rates
n=30 Treatment-naïve=90% pegIFN/RBV treatment experienced=10%	12 weeks	Arm D	ABT-493 (300mg) + ABT-530 (120mg) once daily	93% (n=28/30)
n=30 Treatment-naïve=93% pegIFN/RBV treatment experienced=7%		Arm E	ABT-493 (200mg) + ABT-530 (120mg) once daily	93% (n=28/30)
n=31 Treatment-naïve=90% pegIFN/RBV treatment experienced=10%		Arm F	ABT-493 (200mg) + ABT-530 (120mg) once daily + RBV (weight-based, 1000 or 1200mg) twice daily	94% (n=29/31)
n=30 Treatment-naïve=93% pegIFN/RBV treatment experienced=7%		Arm G	ABT-493 (200mg) + ABT-530 (40mg) once daily	83% (n=25/30)

About AbbVie's HCV Clinical Development Program
AbbVie's HCV clinical development program is intended to advance scientific knowledge and the clinical care of people with chronic HCV infection by investigating pan-genotypic (genotypes 1-6), all-oral, ribavirin-free, once-daily treatment options including shorter (8-12 weeks) duration therapy. AbbVie's investigational regimen includes ABT-493, an NS3/4A protease inhibitor, and ABT-530, an NS5A inhibitor. ABT-493 and ABT-530 are currently being evaluated in Phase 2 studies with a multinational Phase 3 program in genotypes 1 through 6 initiated in November 2015.

ABT-493 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-493 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of hepatitis C.

About AbbVie AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

Forward-Looking Statements  Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission.  AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

¹ Poordad, F., et al. SURVEYOR-I: 98% – 100% SVR4 in HCV Genotype 1 Non-Cirrhotic Treatment-Naïve or Pegylated Interferon/Ribavirin Null-Responders with the Combination of the Next Generation NS3/4A Protease Inhibitor ABT-493 and NS5A Inhibitor ABT-530; Oral presentation #41; presented at The Liver Meeting^®, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, November 13-17, 2015.

² Wyles, D., et al. SURVEYOR-II: High SVR4 Rates Achieved With the Next Generation NS3/4A Protease Inhibitor ABT-493 and NS5A Inhibitor ABT-530 in Non-Cirrhotic Treatment-Naïve and Treatment-Experienced Patients With HCV Genotype 2 Infection; Oral presentation #250; presented at The Liver Meeting^®, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, November 13-17, 2015.

³ Kwo, P, et al. SURVEYOR-II: High SVR4 Rates Achieved With the Next Generation NS3/4A Protease Inhibitor ABT-493 and NS5A Inhibitor ABT-530 In Non-Cirrhotic Treatment-Naïve and Treatment-Experienced Patients With HCV Genotype 3 Infection; Oral presentation #248; presented at The Liver Meeting^®, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, November 13-17, 2015.

⁴ Poordad, F., et al. 100% SVR4 in HCV Genotype 1 Non-Cirrhotic Treatment-Naïve or -Experienced Patients With the Combination of ABT-493 and ABT-530 for 8 Weeks (SURVEYOR-I); Poster presentation #LB-14; presented at The Liver Meeting^®, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco,November 13-17, 2015.

SOURCE AbbVie

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