Lack of insurance bars some from hepatitis C treatment

Lack of insurance bars some from hepatitis C treatment



By Kathryn Doyle

(Reuters Health) - Survey data from 2001 to 2010 show that lack of insurance kept some people with hepatitis C virus from getting treatment.

Recently, more effective and well-tolerated drugs have been developed to treat hepatitis C, removing many of the discouraging side effects of older drugs. The infection is curable and transmission can be prevented, researchers write in the American Journal of Gastroenterology.

But for the more than three million people in the U.S. who have chronic liver disease from hepatitis C, there are still two important barriers to getting treatment, said lead author Dr. Ivo Ditah from the Mayo Clinic in Rochester, Minnesota.

First, many people with the disease do not know they have it, because they feel no symptoms. Once they've been screened and tested positive, those without health insurance or with poor health insurance likely cannot afford the $250,000 to $350,000 price tag for medications and facility fees, Ditah said.

For the new study, he and his coauthors used National Health and Nutrition Examination Survey data, which includes blood testing for infections like hep C, from 2001 to 2010.

Of 38,025 people sampled, 502 tested positive for hep C and 205 were available six months later for follow-up testing. The rest, who tended to be less educated, injecting drugs or not have health insurance, could not be reached.

Half of those 205 patients said they were not aware of their infection until the surveys were done, and 166 pursued further testing or evaluation, but only 18 received therapy. Lack of health insurance coverage was the only predicting factor for who would not receive treatment.

“I think the message remains very strong that a lack of health insurance is going to be a major stumbling block,” Ditah told Reuters Health by phone. “We see a lot of denials from insurance companies not to cover these medications. It’s a huge problem.”

Hep C can be spread by sharing needles, being born to a mother who has the infection, and less commonly through sexual contact. Until the early 1990s, it could also be spread by blood transfusions, but now blood banks can test for the virus in stored blood.

Chronic liver infection can result in long-term health problems, including liver damage, liver failure, liver cancer, or even death, according to the Centers for Disease Control and Prevention. Hepatitis C is the leading cause of cirrhosis and liver cancer and the most common reason for liver transplantation in the U.S.

Up to 25 percent of people who get chronic hepatitis C will clear the virus on their own, while the rest require treatment, according to the CDC.

As newer versions of the best treatments are developed, those in use now will gradually become less expensive, and insurance coverage under the Affordable Care Act has expanded since 2010, Ditah said.

As more people get health insurance, the proportion of people with the infection who cannot be reached will continue to go down, he said.

The CDC recommends that all people of the “baby boomer” generation, born between 1945 and 1965, be screened for hepatitis C.

“Those recommendations should be followed. If they are found to have the infection then a good chunk will get treatment," unless they don't have good health insurance, Ditah said.

SOURCE: http://bit.ly/1BDtym6 American Journal of Gastroenterology, online March 10, 2015

Read more: http://www.reuters.com/article/2015/03/24/us-hepatitis-drugs-access-idUSKBN0MK1WA20150324

Canadian Liver Foundation Applauds Provinces on Providing Access to Interferon-Free Therapy for Hepatitis C Patients

Related - 
Multiple Canadian Provinces to Provide Public Funding for Gilead's Harvoni™

Canadian Liver Foundation Applauds Provinces on Providing Access to Interferon-Free Therapy for Hepatitis C Patients
Collaborative Negotiations Successful in Removing Financial Barrier to Care for Many Patients but Testing Required to Identify Those Still Undiagnosed

TORONTO, ON -- (Marketwired) -- 03/24/15 -- For thousands of Canadians with hepatitis C, the news that the majority of the provinces and territories have worked together to negotiate an agreement to provide access to one of the newest interferon-free drug therapies comes as a welcome relief. The Canadian Liver Foundation applauds this positive move that recognizes the urgent need to treat individuals who have been living with hepatitis C for years, even decades, and are now suffering from advanced liver disease.

"Hepatitis C treatment has evolved dramatically and we have finally reached a point where we have drug therapies that are easy to take, have few, if any, side effects and are highly effective ," says Dr. Morris Sherman, Chairman of the Canadian Liver Foundation. "Unfortunately, the cost put them out of reach of the very patients who needed them the most. Thanks to this collaborative effort, the financial barrier has been removed for many patients in regions across the country."

British Columbia, Ontario, New Brunswick, Yukon and Manitoba have announced that the drug will be added to their formularies with several provinces planning to make similar listing decisions in the coming days and weeks.

Hepatitis C is responsible for almost half of all liver transplants and is a major contributor to the steady rise of liver cancer in Canada. The Canadian Liver Foundation's 2013 report -- Liver Disease in Canada: A Crisis in the Making -- revealed that liver-related deaths had risen by almost 30 per cent in a period of only eight years, due in part to hepatitis C.

While the accessibility of treatment is a critical part of eliminating hepatitis C, it is equally important to identify the thousands of Canadians who are still unaware that they are living with this disease.

"Hepatitis C is common in Canada and up to 70% may still be undiagnosed. No one ever thinks that they could have hepatitis C and more often than not, neither do their doctors," says Dr. Sherman. "Currently Canada uses risk-based testing which hasn't been effective in identifying all infected adults. In fact, as few as 30% have been diagnosed but middle-aged adults account for about 75% of all infected individuals in Canada. These people are at greatest risk of dying from the complications of this disease because the complications become more frequent with age. We need to introduce widespread screening not just based on risk factors but by age. The earlier patients are identified, the better the chances are that they can be effectively treated."

In August 2012, the U.S. Centers for Disease Control issued a recommendation that all adults born between 1945 and 1965 should have a one-time hepatitis C test. Based on the prevalence data in Canada and taking into account immigration from countries where hepatitis C is common, the Canadian Liver Foundation believed the age bracket should be expanded and issued its own recommendations in 2012 that all adults born between 1945 and 1975 should be screened. The Public Health Agency of Canada (PHAC) did its own feasibility studies, convened a working group of experts and created draft age-based recommendations. Revised screening recommendations have not yet been issued publicly.

Studies have shown that age-based hepatitis C testing not only could identify up to 70% of those infected1 but also would be cost-effective2 whereas continuing to rely on risk-based screening will lead to a dramatic rise in liver cancer (205%) and liver-related deaths (160%) by 20353.

"We can now talk to patients about 'when' they are cured, versus 'if'," says Dr. Sherman. "If we do not seek out and inform patients that they have this disease however, we may be sentencing them to unnecessary suffering and death. This week's news is an exciting step forward in our efforts to eliminate hepatitis C and it is our hope that it will be a catalyst for PHAC and the provincial governments to take the follow-up step and implement age-based testing."

About the Canadian Liver Foundation
Founded in 1969, the Canadian Liver Foundation (CLF) was the first organization in the world devoted to providing support for research and education into the causes, diagnoses, prevention and treatment of all liver disease. Today we are the largest charitable funder of liver-related research and we are committed to bringing liver research to life by promoting liver health, improving public awareness and understanding of liver disease and providing support to individuals affected by liver disease. To learn more or to make a donation, visit www.liver.ca.

References:
1 A Canadian screening program for hepatitis C: Is now the time? CMAJ October 15, 2013 vol. 185 no. 15
2 Cost-effectiveness of screening for hepatitis C in Canada CMAJ January 12, 2015
3 Burden of disease and cost of chronic hepatitis C infection in Canada. Can J Gastroenterol Hepatol. 2014 May;28(5):243-50.

Melanie KearnsCanadian Liver Foundation 416-491-3353 ext. 4923mkearns@liver.ca

Source: @ Canadian Liver Foundation

Using Ledipasvir/Sofosbuvir in Cirrhotic, Treatment-Experienced GT1 Patients: 12 Weeks With Ribavirin or 24 Weeks Without?

Using Ledipasvir/Sofosbuvir in Cirrhotic, Treatment-Experienced GT1 Patients: 12 Weeks With Ribavirin or 24 Weeks Without?

Ira M. Jacobson, MD - 3/23/2015 More from this author

The recently updated AASLD/IDSA HCV management guidance recommends the following regimens for treatment-experienced patients with genotype 1 HCV infection who have compensated cirrhosis and who experienced previous treatment failure with peginterferon and ribavirin:
Ledipasvir/sofosbuvir for 24 weeks (rating: class I, level A)
Ledipasvir/sofosbuvir plus ribavirin for 12 weeks (rating: class I, level B)
Ombitasvir/paritaprevir/ritonavir plus dasabuvir and ribavirin for 12 weeks if genotype 1b HCV and for 24 weeks if genotype 1a HCV (rating: class I, level A)
Sofosbuvir plus simeprevir with or without ribavirin for 24 weeks (rating: class IIa, level B)

In this ClinicalThought commentary, I focus on considerations for the use of ledipasvir/sofosbuvir in treatment-experienced patients with genotype 1 HCV infection and cirrhosis. In an upcoming commentary, Paul Y. Kwo, MD, will have a discussion about the use of ombitasvir/paritaprevir/ritonavir and dasabuvir in this setting.

Multiple Options: How to Choose?
In 2015, we are fortunate to have so many highly effective and tolerable options to consider for our patients, particularly those who have already experienced treatment failure following a challenging course of interferon-based therapy and who are in great need of treatment due to advanced fibrosis or cirrhosis. The key remaining challenge is in selection of therapy. When considering the use of ledipasvir/sofosbuvir, the guidance provides 2 options for this group of patients: a 24-week course without ribavirin or a 12-week course with ribavirin. So what is my approach to this decision for my patients?

Data Supporting Ledipasvir/Sofosbuvir Without Ribavirin for 24 Weeks
The recommendation for the use of a 24-week ribavirin-free regimen is based on data from the ION-2 study, which enrolled previously treated patients with genotype 1 HCV infection, 20% of whom had cirrhosis. The SVR rates in ION-2 were 94% and 96% with 12 weeks of ledipasvir/sofosbuvir, without and with ribavirin, respectively, vs 99% with 24 weeks of ledipasvir/sofosbuvir regardless of the addition of ribavirin. When the investigators analyzed the data, they found that the slight arithmetic difference between 12 and 24 weeks of therapy was driven by the subgroup of patients with cirrhosis who had SVR rates of 86% without ribavirin and 82% with ribavirin when treated for 12 weeks vs 100% with or without ribavirin when treated for 24 weeks. Although each of the 4 groups with cirrhosis included only 22 patients, the data strongly suggested that 24 weeks of therapy was optimal when using ledipasvir/sofosbuvir in treatment-experienced patients with cirrhosis and that ribavirin is not necessary. Therefore, the FDA-approved prescribing information recommends 24 weeks of ledipasvir/sofosbuvir without ribavirin for this group of patients.

Data Supporting Ledipasvir/Sofosbuvir Plus Ribavirin for 12 Weeks
One of the most notable stories that emerged at the 2014 AASLD annual meeting was an unexpected resurgence of interest in the use of ribavirin in this setting because of 2 reports suggesting that adding ribavirin to ledipasvir/sofosbuvir for 12 weeks may confer an advantage over ribavirin-free therapy for 12 weeks in treatment-experienced patients with genotype 1 HCV infection and cirrhosis, yielding an SVR rate that approached or even matched the SVR rates conferred by 24 weeks of ledipasvir/sofosbuvir without ribavirin. As the presenter noted from the podium, these data have the potential to create a paradigm shift in how ledipasvir/sofosbuvir is used in this population relatively soon after its approval.

Specifically, the 2 reports in question were from the SIRIUS study by Bourlière and colleagues and an integrated analysis of data from multiple studies. SIRIUS was a well-designed, placebo-controlled study comparing 12 weeks of ledipasvir/sofosbuvir plus ribavirin vs 24 weeks of ledipasvir/sofosbuvir without ribavirin in patients with genotype 1 HCV infection and cirrhosis who experienced previous treatment failure with peginterferon/ribavirin plus telaprevir or boceprevir. The SVR rates were 96% with the 12-week regimen and 97% with the 24-week regimen. This study included 154 cirrhotic patients, a larger number than the 88 patients with cirrhosis enrolled in ION-2.

In the integrated analysis, the same group of investigators evaluated data from 513 patients with cirrhosis—both treatment experienced and treatment naive—across the entire development program for ledipasvir/sofosbuvir, into which the data from the SIRIUS study were incorporated. Among treatment-experienced patients with cirrhosis, the results demonstrated a 90% SVR rate with ledipasvir/sofosbuvir alone for 12 weeks vs 96% with ledipasvir/sofosbuvir plus ribavirin for 12 weeks. The SVR rates with 24 weeks of treatment were 98% and 100% without and with ribavirin, respectively. This sparked much discussion about the potential to conserve resources and reduce costs by administering only 12 weeks of ledipasvir/sofosbuvir plus ribavirin with equivalent results to those achieved with the approved regimen of ledipasvir/sofosbuvir alone for 24 weeks in treatment-experienced patients with cirrhosis. Many hepatologists appeared quite ready to embrace the 12-week regimen with ribavirin as their new standard of practice when using ledipasvir/sofosbuvir in this patient population, whereas others seemed more hesitant to do so.

Concerns With Ledipasvir/Sofosbuvir Plus Ribavirin for 12 Weeks
My opinion, cost differences aside, is based on the data from the integrated analysis showing an SVR rate of 96% with 12 weeks of ledipasvir/sofosbuvir plus ribavirin vs 98% to 100% with 24 weeks of ledipasvir/sofosbuvir with or without ribavirin. Even if not statistically significant, this may represent a trend that could result in treatment failure for a small number of patients who receive the 12-week ribavirin-containing regimen vs the 24-week ribavirin-free regimen.

The second concern I have is that all the evidence accumulated to date, including all the data on ledipasvir/sofosbuvir from the ION studies (ION-1 and -3 in treatment-naive and ION-2 in treatment-experienced patients) and the real-world data on sofosbuvir-based regimens from the TRIO and HCV-TARGET databases, has failed to provide a hint that adding ribavirin confers an incremental benefit in the efficacy of sofosbuvir-based therapy. Clinicians who are proposing to immediately start using 12 weeks of ledipasvir/sofosbuvir plus ribavirin in treatment-experienced patients with cirrhosis are accepting the idea that ribavirin adds benefit, despite the absence of any other signal across the entire development program or real-world studies and based only on the SIRIUS study and the recent integrated analysis. I find myself reluctant to deviate from what is still the FDA-approved regimen for ledipasvir/sofosbuvir based on that analysis alone. When considering that ribavirin is a relatively weak antiviral agent by itself, with a mechanism of action in combination with either interferon or direct-acting antivirals that is still entirely unclear, I am intuitively hesitant to conclude that adding ribavirin to a 12-week ledipasvir/sofosbuvir regimen can confer the same benefit as continuing 2 potent, well-tolerated direct-acting antiviral agents for 12 additional weeks. It is worth noting that the AASLD/IDSA guidance indicates the lower level of evidence to support the 12-week regimen vs the 24-week regimen by assigning level B, (data derived from a single randomized trial, nonrandomized studies, or equivalent) to the 12-week recommendation and level A data derived from multiple randomized clinical trials, meta-analyses, or equivalent) to the 24-week recommendation.

The Case for Ledipasvir/Sofosbuvir Without Ribavirin for 24 Weeks
In my practice, we follow the FDA-approved prescribing information for ledipasvir/sofosbuvir in treatment-experienced patients with genotype 1 HCV infection and cirrhosis, which indicates 24 weeks of treatment without ribavirin. In addition to an element of residual uncertainty about whether a 12-week regimen with ribavirin is every bit as effective as 24 weeks without ribavirin, there are considerations of tolerability relevant to ribavirin. Although ribavirin is admittedly better tolerated when not coadministered with interferon, particularly regarding anemia, the fact remains that it can cause anemia with 5% to 10% of patients experiencing declines in hemoglobin to < 10 g/dL, which may be problematic in patients such as those with cardiac or pulmonary disease, baseline anemia, or elderly patients. Ribavirin is also a category X drug that mandates strict birth control throughout the duration of therapy, as well as for 6 months thereafter due to potential teratogenicity. Other adverse effects of ribavirin, such as insomnia, pruritus, and nausea, may make 12 weeks of a ribavirin-containing regimen less well tolerated than 24 weeks of therapy with ledipasvir/sofosbuvir alone.

Of course, both regimens represent revolutionary development for the better in the treatment of hepatitis C. However, despite the inclusion of the 12-week, ribavirin-containing ledipasvir/sofosbuvir regimen in the revised AASLD/IDSA guidance, my personal preference when using ledipasvir/sofosbuvir in treatment-experienced patients with genotype 1 HCV infection and cirrhosis is to avoid ribavirin and administer treatment for 24 weeks, as long as I can obtain access to this regimen for my patients. Admittedly, 12 weeks of ledipasvir and sofosbuvir with ribavirin appear to also be a highly effective option.

When I Would Choose Ledipasvir/Sofosbuvir Plus Ribavirin for 12 Weeks
Are there any instances in which I would choose the 12-week course of ledipasvir/sofosbuvir plus ribavirin over the 24-week course of ledipasvir/sofosbuvir alone? Yes—in patients for whom there are anticipated adherence challenges or economic barriers. In these cases, I have a dialogue with my patients to ensure they understand that we are making a decision with potential medical implications, particularly regarding tolerability, on the basis of economic concerns. They should be counseled as to the potential adverse effects, such as anemia and teratogenicity.

Your Thoughts?
I am interested to hear your thoughts. How will you be using ledipasvir/sofosbuvir in treatment-experienced patients with genotype 1 HCV infection and cirrhosis?

Topics: HCV - Treatment, Fibrosis and Cirrhosis - Treatment

Related Discussions

Improving Access to HCV Treatment: The Clinician’s Role

Genotype 3 HCV: Still Difficult to Treat?

Looking Beyond Liver Disease Stage When Determining Need for HCV Therapy

My Take on the Guidance From AASLD/IDSA for Managing Treatment-Experienced Patients With Genotype 3 HCV Infection and Cirrhosis

Source - Clinical Care Options / Clinical Thought

Multiple Canadian Provinces to Provide Public Funding for Gilead's Harvoni™

Gilead's hepatitis C treatment Harvoni accepted in Canadian health reimbursement plan
NEW YORK — Gilead Sciences said multiple Canadian provinces will provide access to the biotechnology company's hepatitis C drug Harvoni following a positive reimbursement recommendation from regulators...

Multiple Canadian Provinces to Provide Public Funding for Gilead's Harvoni™

Gilead Sciences Canada today announced that multiple provinces will provide public access to Harvoni ™ (ledipasvir/sofosbuvir), the first once-daily, single tablet regimen for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection in adults. In Canada, it is estimated that more than 250,000 Canadians are living with chronic HCV infection, with thousands of new cases diagnosed each year. 1 Genotype 1 infection represents an estimated 65 per cent of patient cases.

Public reimbursement comes after a positive recommendation from the Common Drug Review, and as a result of a productive collaboration between Gilead Canada and the Pan-Canadian Pharmaceutical Alliance (pCPA) to ensure participating provinces are able to provide timely access to patients in need of curative treatment. This review, co-led by the BC Ministry of Health and the Ontario Ministry of Health and Long-Term Care, resulted in an agreement with member provinces to fund the innovative therapy for patients.

“We have been waiting for an innovative therapy like Harvoni since interferon was first used to treat the disease,” said Dr. Alnoor Ramji, Clinical Associate Professor of Medicine (Gastroenterology and Hepatology), University of British Columbia. “This is a transformative, interferon-free therapy, with a combination of high cure rates, good tolerability and simplicity of treatment. Harvoni provides patients with the confidence to commit to therapy and a very high probability to achieve a cure.”

Current treatments include interferon and ribavirin that often exclude patients from treatment or lead to early discontinuation of treatment due to associated side effects. Harvoni represents a significant advance in the treatment of genotype 1 HCV infection, the most prevalent genotype in Canada. Harvoni is the only once-daily, single tablet regimen that offers cure rates between 94 and 99 per cent, eliminates the need for interferon and ribavirin, and shortens the duration of treatment to as little as eight weeks for many patients. Eight weeks of treatment with Harvoni can be considered for treatment-naïve patients without cirrhosis who have baseline HCV viral load below 6 million IU/mL. Recently, the Canadian Association for the Study of the Liver updated the Canadian consensus guidelines on the management of hepatitis C and recommended Harvoni as first-line therapy for all genotype 1 patients.

“Today’s announcement recognizes the significant health-system and societal benefits associated with curing this disease and preventing its complications,” said Dr. Paul Marotta, Associate Professor, University of Western Ontario and with London Health Sciences Centre. “Access to Harvoni will help us confront this serious public health issue and start formulating longer-term solutions that may prove relevant to the hepatitis C disease elimination efforts across Canada.”

In a recent article, “Burden of disease and cost of chronic hepatitis C virus infection in Canada,” ( Canadian Journal of Gastroenterology and Hepatology ), leading Canadian hepatitis C specialists highlighted an expected 205 per cent increase in cases of liver cancer, a 160 per cent increase in liver-related deaths, and a 60 per cent increase in total healthcare costs over the next 20 years. 2 Recently, the article was recognized with a scientific award for its groundbreaking research in Canada.

In addition to Harvoni, Gilead Canada’s Sovaldi ® (sofosbuvir) has also been listed for public reimbursement for chronic HCV genotypes 1, 2 and 3 infection in multiple provinces.

“We live in an era of rapid evolution in the treatment of chronic hepatitis C infection, and Gilead Canada is pleased that our collaboration with the pCPA has allowed multiple provinces to recognize the clinical value of Harvoni as a simple, well tolerated and curative therapy for patients living with genotype 1 HCV,” said Edward Gudaitis, General Manager, Gilead Sciences Canada, Inc. “Gilead Canada will continue to work closely with all provinces and territories to bring this cost-effective, once-daily treatment to patients across Canada.”

Source

Fibrosis progression in NAFLD vs NASH

Fibrosis progression in NAFLD vs NASH 

34% had fibrosis progression at follow-up evaluation
Clinical Gastroenterology & Hepatology

View full text article,here

A study in April's Clinical Gastroenterology & Hepatology estimates the rates of fibrosis progression in patients with nonalcoholic fatty liver disease and NASH.

Little is known about differences in rates of fibrosis progression between patients with nonalcoholic fatty liver (NAFL) vs nonalcoholic steatohepatitis (NASH).

Professor Rohit Loomba and colleagues from California, USA conducted a systematic review and meta-analysis of all studies that assessed paired liver biopsy specimens to estimate the rates of fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD) including NAFL and NASH.

Through a systematic search of multiple databases and author contact, up to 2013, the researchers identified studies of adults with NAFLD that collected paired liver biopsy specimens at least 1 year apart.

From these, the team calculated a pooled-weighted annual fibrosis progression rate with 95% confidence intervals, and identified clinical risk factors associated with progression.


The researchers identified 11 cohort studies including 411 patients with biopsy-proven NAFLD.

At baseline, the distribution of fibrosis for stages 0, 1, 2, 3, and 4 was 33%, 33%, 17%, 9%, and 6%, respectively.

The team observed that over 2146 person-years of follow-up evaluation, 34% had fibrosis progression, 43% had stable fibrosis, and 22% had an improvement in fibrosis stage.

The annual fibrosis progression rate in patients with NAFL who had stage 0 fibrosis at baseline was 0.07 stages, compared with 0.14 stages in patients with NASH.

The team found that these findings correspond to 1 stage of progression over 14 years for patients with NAFL, and 7 years for patients with NASH.

Professor Loomba's team commented, "Based on a meta-analysis of studies of paired liver biopsy studies, liver fibrosis progresses in patients with NAFL and NASH."

Clin Gastroenterol Hepatol 2015: 13(4): 643–654.e9
23 March 2015

Dr Reddy's partners Hetero to sell Hepatitis C drug in India

Dr Reddy's partners Hetero to sell Hepatitis C drug in India

Drug to be sold under Resof brand; Company says diagnosis rates for Hepatitis C in India abysmally low

K Rajani Kanth | Hyderabad
March 23, 2015 Last Updated at 17:18 IST

Pharmaceutical major Dr Reddy's Laboratories Limited has entered into an agreement with Hetero Drugs, also from Hyderabad, under which Dr Reddy's has been licenced to distribute and market Sofosbuvir tablets in 400 mg strength in India.

The drug, to be sold under the Resof brand, is indicated for the treatment of chronic Hepatitis C.

With the diagnosis rates for Hepatitis C in India being abysmally low, Dr Reddy's will make a significant difference in the diagnosis and treatment of this disease, Dr Reddy's said in a filing to the exchanges on Monday.

Early this month, Hetero has received approval for generic Sofosbuvir 400 mg tablets from Drug Controller General of India.

The company has a non-exclusive licence agreement with Irish firm Gilead Sciences to manufacture and sell generic versions of its chronic Hepatitis C medicines in 91 developing countries.

According to World Health Organisation (WHO), close to 12 million Indians suffer from chronic Hepatitis C, a disease that can seriously affect the liver, leading to potentially life-threatening complications, including cancer of the liver.

"Clinical studies have indicated that Sofosbuvir 400 mg, in combination with other agents, achieved very high cure rates, while shortening the duration of the treatment to as little as 12 weeks and reducing or completely eliminating the need for interferon injections, depending on the viral genotype," Dr Reddy's said.

"The launch of Resof is in line with Dr Reddy's philosophy of 'innovative medicine at an affordable price' and will provide significant relief to patients, resulting in potential cure and a high barrier to resistance at an affordable price for those living with Hepatitis C," said GV Prasad, co-chairman of Dr Reddy's.

Dr Reddy's Laboratories Limited's scrip ended the trade at Rs 3,448.25 on the BSE on Monday, up 0.56 per cent, over the previous close of Rs 3,428.95 a share.

Source

FDA Update - Important safety information: Harvoni , and Sovaldi‏

Related Update: April 16
FDA approved changes to the Olysio (simeprevir) package insert to include two new Warnings and Precautions;
--serious symptomatic bradycardia when co-administered with sofosbuvir and amiodarone
--hepatic decompensation and hepatic failure.

March 24
FDA - Safety Announcement
Facts about Harvoni and Sovaldi
More Info for Patients
More Info for Health Care Professionals
Data Summary

March 21:

FDA update and Gilead Sciences issued letter to Healthcare Providers;

FDA Hepatitis Update - Important safety information: Harvoni , and Sovaldi‏

Serious and Life-Threatening Cases of Symptomatic Bradycardia as well as One Case of Fatal Cardiac Arrest Reported with Coadministration of amiodarone with either Harvoni® (ledipasvir and sofosbuvir fixed-dose combination) or with Sovaldi® (sofosbuvir) in combination with another direct acting antiviral.

Please see Gilead Sciences has issued a Dear Healthcare Provider letter:
SVD HVN - DHCP Letter 20March15 - FINAL.DOCX - COPY provided below......

On March 20, 2015, FDA approved changes to the Harvoni (ledipasvir/sofosbuvir fixed dose combination) and Sovaldi (sofosbuvir) labels to update the WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS, and DRUG INTERATIONS sections of the labeling and the patient package insert with information on post-marketing cases of symptomatic bradycardia when co-administered with amiodarone. Additionally, Gilead Sciences has issued a Dear Healthcare Provider letter (see below).

The specific changes to the each label are summarized below.

Harvoni label changes:

5 WARNINGS AND PRECAUTIONS

5.1 Serious Symptomatic Bradycardia When Coadministered with Amiodarone

Postmarketing cases of symptomatic bradycardia, including fatal cardiac arrest and cases requiring pacemaker intervention, have been reported when amiodarone is coadministered with HARVONI. Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. Bradycardia generally resolved after discontinuation of HCV treatment. The mechanism for this effect is unknown.

Coadministration of amiodarone with HARVONI is not recommended. For patients taking amiodarone who have no other alternative, viable treatment options and who will be coadministered HARVONI:

• Counsel patients about the risk of serious symptomatic bradycardia

• Cardiac monitoring in an in-patient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.

Patients who are taking HARVONI who need to start amiodarone therapy due to no other alternative, viable treatment options should undergo similar cardiac monitoring as outlined above.

Due to amiodarone’s long half-life, patients discontinuing amiodarone just prior to starting HARVONI should also undergo similar cardiac monitoring as outlined above.

Patients who develop signs or symptoms of bradycardia should seek medical evaluation immediately.

6 ADVERSE REACTIONS

6.2 Postmarketing Experience

Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been identified during post approval use of HARVONI.

7 DRUG INTERACTIONS

Added amiodarone information to Table 3, Potentially Significant Drug Interactions: Alterations in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction.

Concomitant Drug Class: Drug Name	Effect on Concentration	Clinical Comment
Antiarrhythmics: amiodarone	Effect on amiodarone, ledipasvir, and sofosbuvir concentrations unknown	Coadministration of HARVONI with amiodarone may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. Coadministration of amiodarone with HARVONI is not recommended; if coadministration is required, cardiac monitoring is recommended [see Warnings and Precautions (5.1)]

Sovaldi Label Changes:

5 WARNINGS AND PRECAUTIONS

5.1 Serious Symptomatic Bradycardia When Coadministered with Amiodarone and Another HCV Direct Acting Antiviral

Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with SOVALDI in combination with an investigational agent (NS5A inhibitor) or simeprevir. A fatal cardiac arrest was reported in a patient receiving a sofosbuvir-containing regimen (HARVONI (ledipasvir/sofosbuvir)). Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. Bradycardia generally resolved after discontinuation of HCV treatment. The mechanism for this effect is unknown.

Coadministration of amiodarone with SOVALDI in combination with another direct acting antiviral (DAA) is not recommended. For patients taking amiodarone who have no other alternative, viable treatment options and who will be coadministered SOVALDI and another DAA:

• Counsel patients about the risk of serious symptomatic bradycardia

• Cardiac monitoring in an in-patient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.

Patients who are taking SOVALDI in combination with another DAA who need to start amiodarone therapy due to no other alternative, viable treatment options should undergo similar cardiac monitoring as outlined above.

Due to amiodarone’s long half-life, patients discontinuing amiodarone just prior to starting SOVALDI in combination with a DAA should also undergo similar cardiac monitoring as outlined above.

Patients who develop signs or symptoms of bradycardia should seek medical evaluation immediately. Symptoms may include near-fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pains, confusion or memory problems [See Adverse Reactions (6.2), Drug Interactions (7.2)].

6 ADVERSE REACTIONS

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of SOVALDI. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac Disorders

Serious symptomatic bradycardia has been reported in patients taking amiodarone who initiate treatment with SOVALDI in combination with another HCV direct acting antiviral [See Warnings and Precautions (5.1), Drug Interactions (7.2)].

7 DRUG INTERACTIONS

Added amiodarone information to Table 5, Potentially Significant Drug Interactions: Alterations in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction.

Concomitant Drug Class: Drug Name	Effect on Concentration	Clinical Comment
Antiarrhythmics: amiodarone	Effect on amiodarone and sofosbuvir concentrations unknown	Coadministration of amiodarone with SOVALDI in combination with another DAA may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. Coadministration of amiodarone with SOVALDI in combination with another DAA is not recommended; if coadministration is required, cardiac monitoring is recommended [See Warnings and Precautions (5.1), Adverse Reactions (6.2)].

Updated labeling will be posted soon at DailyMed

Please see Gilead Sciences has issued a Dear Healthcare Provider letter:

SVD HVN - DHCP Letter 20March15 - FINAL.DOCX - COPY provided below......

Harvoni and Sovaldi are products of Gilead Sciences.

Richard Klein

Office of Special Health Issues

Food and Drug Administration

Kimberly Struble

Division of Antiviral Drug Products

Food and Drug Administration

Steve Morin

Office of Special Health Issues

Food and Drug Administration

Gilead Sciences issued letter to Healthcare Providers 

FDA Hepatitis Update - Important safety information: Harvoni , and Sovaldi

IMPORTANT DRUG WARNING

Subject: Serious and Life-Threatening Cases of Symptomatic Bradycardia as well as One Case of Fatal Cardiac Arrest Reported with Coadministration of Amiodarone With Either Harvoni® (ledipasvir and sofosbuvir fixed-dose combination) or With Sovaldi® (sofosbuvir) in Combination with Another Direct Acting Antiviral.

Dear Health Care Provider,
The purpose of this letter is to inform you of new important safety information for Harvoni and Sovaldi

· Harvoni is indicated for the treatment of chronic hepatitis C genotype 1 infection in adults.
· Sovaldi is indicated for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen.

Serious Risk of Symptomatic Bradycardia With Co-Use of Amiodarone with Either Harvoni or With Sovaldi in Combination with Another Direct Acting Antiviral (DAA)

· Postmarketing cases of symptomatic bradycardia, as well as one fatal cardiac arrest and cases requiring pacemaker insertion, have been reported in patients taking amiodarone and Harvoni, or amiodarone and Sovaldi in combination with another DAA.
· Bradycardia was observed within hours to days of starting Harvoni, or Sovaldi in combination with another DAA, but cases have been observed up to 2 weeks after initiating HCV treatment.
· Risk factors for the development of symptomatic bradycardia in patients receiving amiodarone may include coadministration of a beta blocker, or those with underlying cardiac comorbidities and/or advanced liver disease.
· Similar cases have not been reported in patients receiving Sovaldi with ribavirin or with pegylated interferon and ribavirin.

Warning and Precaution
Coadministration of amiodarone with either Harvoni or with Sovaldi in combination with another DAA is not recommended.

Further Information

Nine cases of symptomatic bradycardia have been reported during postmarketing in patients receiving amiodarone with either Harvoni, or Sovaldi in combination with another DAA (daclatasvir, an investigational DAA, or Olysio (simeprevir)). Seven patients were also receiving a beta blocker.

· Six cases occurred within the first 24 hours and the remaining 3 cases occurred within the first 2-12 days following HCV treatment initiation.
· One case was a fatal cardiac arrest and 3 cases required pacemaker intervention.
· In 3 cases, rechallenge with HCV treatment in the setting of continued amiodarone therapy resulted in recurrence of symptomatic bradycardia.
· In one case discontinuation of amiodarone followed by rechallenge of HCV treatment after 8 weeks did not result in recurrent bradycardia.
· Three of the 9 cases were in patients receiving Harvoni, 5 cases were in patients receiving Sovaldi plus an investigational agent (daclatasvir) and 1 case was in a patient receiving Sovaldi with Olysio (simeprevir).

The mechanism of the potential interaction between amiodarone and Harvoni, or Sovaldi in combination with another DAA is unknown.

Because the number of patients taking amiodarone who have been exposed to Harvoni or Sovaldi in combination with another DAA is unknown, it is not possible to estimate the incidence of occurrence of these events.

Prescriber Action
For patients taking amiodarone who have no other alternative, viable treatment options and who will be co-administered Harvoni, or Sovaldi in combination with another DAA:
· Counsel patients about the risk of serious symptomatic bradycardia
· Cardiac monitoring in an in-patient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.

Patients who are taking Harvoni or Sovaldi in combination with another DAA who need to start amiodarone therapy due to no other alternative, viable treatment options should undergo similar cardiac monitoring as outlined above.

Due to amiodarone’s long half-life, patients discontinuing amiodarone just prior to starting Harvoni or Sovaldi in combination with a DAA should also undergo similar cardiac monitoring as outlined above.

Tell your patients if they develop signs or symptoms that might suggest symptomatic bradycardia they should seek medical evaluation immediately. Symptoms may include:

· Near-fainting or fainting
· Excessive tiredness
· Dizziness or lightheadedness
· Shortness of breath
· Malaise
· Chest pains
· Weakness
· Confusion or memory problems

Patients should not stop taking any of their medicines without talking to their healthcare provider.
This information is based on currently available data and recommendations may change. Additionally, the product labeling will be updated.

Reporting Adverse Events

Please report all adverse events, following or coincident with the use of Harvoni or Sovaldi, to Gilead Global Drug Safety at 1-800-GILEAD-5, option 3; or to FDA's MedWatch program by telephone at 1-800-332-1088; by fax at 1-800-332-0178; via www.FDA.gov/medwatch; or by mail to MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20857 (use postage-paid FDA Form 3500).

Please refer to the accompanying full prescribing information and approved patient information for a complete description of the risk profile for Harvoni or Sovaldi.
Contact Gilead Medical Information at 1-800-GILEAD-5, option 2 if you have additional questions.

This information is being sent in agreement with the FDA.

Sincerely,
John McHutchison, MD
Executive Vice President, Clinical Research
Gilead Sciences, Inc.
Download - SVD HVN - DHCP Letter 20March15 - FINAL.DOCX

Gilead Sciences gathering details of buyers of hepatitis-C drug to prevent its diversion

Gilead Sciences gathering details of buyers of hepatitis-C drug to prevent its diversion

Gilead Sciences is collecting details of patients who buy generic versions of hepatitis-C medicine Sofosbuvir to ensure that stocks aren’t diverted to other markets.

DIVYA RAJAGOPAL  |  20 March 2015, 11:30 AM IST

MUMBAI: Gilead Sciences is collecting details of patients who buy generic versions of its blockbuster hepatitis-C medicine Sofosbuvir, on which it had signed voluntary licensing deals with several Indian companies, people with knowledge of the matter said. The move, aimed at ensuring that the stocks meant for local supplies aren't diverted to other markets, has raised concerns among activists.

Under the licensing agreements, US company had asked local partners to put in place an anti-diversion strategy and, as part of that, they are collecting each patient's phone number and the name of the doctor who prescribed the drug through chemists, the people said. The drug's distributors have been told to keep a record of the sales.

Gilead's overcautious move is a result of dual pricing that it has introduced for the drug. In India, the generic versions of the drug are priced at $900 (Rs 56,400) for a 12-week treatment, compared with $84,000 in the western markets for Sofosbuvir. And, with several generic makers in the fray, the drug might cost lower than $900 in some 90 countries.

Gilead didn't respond to an email seeking comment. One of its generic partners confirmed, on the condition of anonymity, that it has been instructed to maintain records on the contact details of Indian patients.

"With this pre-condition of revealing one's details, patients have no choice but to give in, if they want to access this drug," said Shiba Phurailatpam of the Asia Pacific Network, an organisation that works with HIV-positive people. Hepatitis C and B are common among people who are living with HIV.

Leena Menghaney, regional head of MSF South Asia, said companies aren't authorised to collect the identities (name and phone numbers) of hepatitis-C positive patients who procure medicines in India. "As HIV activists we fought hard for confidentiality rights for people living with HIV to ensure that patients were not faced with discrimination and misuse of their medical data," she said, while warning that the conditions to sell the drug could lead to serious human rights violations, if the data were abused.

Last year, Gilead gave voluntary licenses to seven Indian drug companies to manufacture and sell generic versions of Sofosbuvir in 91 countries, excluding western markets and a few countries in Asia. It fears that the drug, made available in these markets at a fraction of the branded version's selling price, could find its way to developed markets. So, it is looking to account for every dosage sold.

Gilead asked partners to put in place the antidiversion strategy to help prevent the drug being routed to western markets, the sources said. In countries like Pakistan and Egypt, Gilead has instructed its distributors to sell new stocks only after patients return the empty bottles of previously purchased drugs.

Natco Pharma, a Gilead partner that has launched the drug in the local market last week, refused to comment. Zydus Cadila, which announced the launch of the drug, couldn't be reached for comment, despite repeated phone call to a senior executive.

In India, only companies that sell drugs that come under Schedule X have to keep such stringent records of distribution.

"Companies and chemists have no business collecting patients' details; personal information about a patient stays with doctors alone," said Anand Grover, senior advocate with Lawyers Collective. 

Source

Related

Fact sheet: Gilead's chronic hepatitis C treatment restrictions

Gilead Sciences and several Indian companies which have entered into an agreement with Gilead to produce hepatitis C drugs, Médecins Sans Frontières/Doctors Without Borders (MSF) urged the generic companies to reject a highly-controversial programme that could compromise people’s treatment and confidentiality.