Hepatitis C - Generic sofosbuvir-based interferon-free direct acting antiviral agents: a real-world multicenter observational study

In The News

Monday, September 24, 2018

Gilead Subsidiary to Launch Authorized Generics of Epclusa® (Sofosbuvir/Velpatasvir) and Harvoni® (Ledipasvir/Sofosbuvir) for the Treatment of Chronic Hepatitis C 

-- List Price of Authorized Generics to Reflect Discounts in the System Today -- 

Generic sofosbuvir-based interferon-free direct acting antiviral agents for patients with chronic hepatitis C virus infection: a real-world multicenter observational study

Chen-Hua Liu, Yi-Jie Huang, Sien-Sing Yang, Chung-Hsin Chang, Sheng-Shun Yang, Hsin-Yun Sun, Chun-Jen Liu, Wen-Chun Liu, Tung-Hung Su, Hung-Chih Yang, Chun-Ming Hong, Tai-Chung Tseng, Pei-Jer Chen, Ding-Shinn Chen, Chien-Ching Hung & Jia-Horng Kao

Full-Text Article 

Scientific Reports volume 8, Article number: 13699 (2018)

Published: 12 September 2018 

Abstract

Real-world data regarding the effectiveness and safety of generic sofosbuvir (SOF)-based interferon-free direct acting antiviral agents (DAAs) for patients with chronic hepatitis C virus (HCV) infection remain limited. A total of 517 chronic HCV-infected patients receiving 12 or 24 weeks of SOF-based therapies were retrospectively enrolled in 4 academic centers in Taiwan. The rate of sustained virologic response at week 12 off-therapy (SVR12) and that of treatment completion were assessed. The baseline characteristics and on-treatment HCV viral kinetics to predict SVR12 were analyzed. By evaluable population (EP) analysis, the SVR12 rate was 95.4% (95% confidence interval [CI]: 93.2–96.9%). The SVR12 was achieved in 29 of 34 patients (85.3%, 95% CI: 69.6–93.6%), 130 of 139 patients (93.5%, 95% CI: 88.2–96.6%), 119 of 124 patients (96.0%, 95% CI: 90.9–98.3%) and 215 of 220 patients (97.7%, 95% CI: 94.8–99.0%) who received SOF in combination with ribavirin (RBV), ledipasvir (LDV), daclatasvir (DCV) and velpatasvir (VEL), respectively. Of 517 patients, 514 (99.4%) completed the scheduled treatment. All 15 patients with true virologic failures were relapsers. Two decompensated cirrhotic patients had on-treatment deaths which were not related to DAAs. All 7 patients who were lost to follow-up had undetectable HCV RNA level at the last visit. The SVR12 rates were comparable in terms of baseline patient characteristics and viral decline at week 4 of treatment. In conclusion, generic SOF-based regimens are well tolerated and provide high SVR12 rates in patients with chronic HCV infection.

Introduction
Hepatitis C virus (HCV) infection remains a challenging health problem in the world. It is estimated that approximately 71.1 million people, which account for 1.0% of the world’s population, are HCV carriers1. Among patients with chronic HCV infection, about 20% of them will evolve to cirrhosis over a period of 20–30 years. Once cirrhosis is established, the annual rates of developing hepatic decompensation and hepatocellular carcinoma (HCC) are 3–6% and 1–4%, respectively2,3. In addition to increasing the risks of liver-related morbidity and mortality, HCV infection is also associated with various extra-hepatic manifestations which further compromised the patients’ health outcome and quality of life4. On the other hand, the morbidity and mortality are significantly reduced once these patients achieve sustained virologic response (SVR) by anti-HCV agents5,6,7,8,9.

The use of interferon (IFN)-free direct acting antiviral agents (DAAs) has made a paradigm shift and become the standard of care for HCV infection. Sofosbuvir (SOF) is a pyrimidine nucleotide analogue that inhibits the HCV non-structural protein 5B (NS5B) ribonucleic acid (RNA)-dependent RNA polymerase, which is essential for viral replication. After intra-hepatic metabolism to active uridine triphosphate form, the GS-461203, it is incorporated to HCV RNA by NS5B polymerase and acts as the chain terminator10. Clinically, SOF is administered once-daily with pangenotypic potency, well tolerability, a high genetic barrier to drug resistance, and low rates of drug-drug interactions (DDIs). Furthermore, SOF can be used in combination with various kinds of NS3/4 A protease inhibitors (PIs), NS5A inhibitors, and/or ribavirin (RBV) to achieve high SVR rates11,12,13,14,15,16,17,18,19,20,21,22,23. Because of the excellent therapeutic profiles, treatment of HCV by SOF-based regimens is appealing to most health care providers.

Although SOF-based IFN-free DAAs are highly efficacious and well tolerated, many HCV-infected individuals have limited governmental reimbursement or private insurance support for brand-name agents24,25,26. Allowing generic SOF-based DAAs through voluntary or compulsory licensing can scale up the HCV treatment to facilitate more efficient HCV control, particularly for patients in resource-constrained countries. Regarding the effectiveness and safety of generic SOF in combination with ledipasvir (LDV), daclatasvir (DCV), and/or RBV, several reports from China, India, Egypt and Argentina indicated that the SVR rates were >90% and most patients tolerated the treatment well27,28,29,30,31. On the basis of these encouraging results, we aimed to evaluate the performance of generic SOF-based DAAs for HCV and factors potentially affecting the treatment response in a multicenter cohort in Taiwan.

Open Access

Full-Text Article Available Online:

https://www.nature.com/articles/s41598-018-32060-7

Hepatitis drugs more affordable but disease still deadly: WHO

Hepatitis drugs more affordable but disease still deadly: WHO

Stephanie Nebehay

GENEVA (Reuters) - Prices of drugs to cure hepatitis C and to treat hepatitis B are dropping dramatically, offering affordability and hope to 325 million people living with the viral liver disease that can be fatal, the World Health Organisation (WHO) said on Thursday. A generic antiviral drug for hepatitis C, which can be cured in three months, was placed this week on WHO's list of pre-qualified medicines.

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Related On This Blog

The controversy over expensive new drugs for hepatitis C
Link to research and news articles addressing the high cost of hepatitis C drugs; insurance restrictions - private insurers/Medicaid - and availability of generic versions/India, Egypt and other lower-income countries or through online "buyers clubs"

Hepatitis C - Mylan Receives WHO Prequalification for Generic Sovaldi®

Mylan Receives WHO Prequalification for Generic Sovaldi®

First Generic Prequalification for Sofosbuvir Tablets

HERTFORDSHIRE, England and PITTSBURGH, July 26, 2017 /PRNewswire/ -- Mylan N.V. (NASDAQ, TASE: MYL), a leading global pharmaceutical company, today announced receipt of approval from the World Health Organization Prequalification of Medicines Program (WHO PQ) of its application for Sofosbuvir Tablets, 400 mg, a generic version of Gilead Sciences' Sovaldi®. Sofosbuvir, a directly acting antiretroviral, will be available in developing countries to treat hepatitis C.

Mylan's Sofosbuvir Tablets, 400 mg, which are produced under license from Gilead Sciences, are the first generic version to be approved under the WHO PQ Program. With WHO PQ approval, international donors and purchasers, such as UNITAID and U.N. agencies, will able to fund and procure the product, and other buyers can be assured of the product's quality, safety and efficacy.

"This marks another important step in Mylan's leadership to help fight infectious diseases around the world," commented Mylan President Rajiv Malik. "It also furthers our mission of increasing access to high quality, affordable medicines to patients, healthcare practitioners, governments and other stakeholders to help treat hepatitis C."

Worldwide, there are more than 70 million people living with chronic hepatitis C, which results in nearly 400,000 related deaths every year. (1) The WHO estimates that antiviral medication can cure more than 95% of chronic hepatitis C cases. (2)

About Mylan
Mylan is a global pharmaceutical company committed to setting new standards in healthcare. Working together around the world to provide 7 billion people access to high quality medicine, we innovate to satisfy unmet needs; make reliability and service excellence a habit; do what's right, not what's easy; and impact the future through passionate global leadership. We offer a growing portfolio of more than 7,500 marketed products around the world, including antiretroviral therapies on which approximately 50% of people being treated for HIV/AIDS in the developing world depend. We market our products in more than 165 countries and territories. We are one of the world's largest producers of active pharmaceutical ingredients. Every member of our more than 35,000-strong workforce is dedicated to creating better health for a better world, one person at a time. Learn more at Mylan.com.

(1, 2) http://www.who.int/mediacentre/factsheets/fs164/en/

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WHO prequalifies first generic hepatitis C medicine and first HIV self-test

In the lead-up to Paris AIDS conference, WHO prequalifies first generic hepatitis C medicine and first HIV self-test

Hepatitis C
WHO today prequalified the first generic version of sofosbuvir, a critical medicine for the treatment of hepatitis C. The development could expand access to treatment by increasing the number of quality-assured generic medicines on the market. Sofosbuvir, 400 mg tablet, is manufactured by Mylan Laboratories Ltd., India.

“This is a break-through medicine with a 95% cure,” said Dr Suzanne Hill, Director, Essential Medicines and Health Products at WHO. “The first WHO-prequalified generic of this product will give large procurers and countries the assurance of quality for an affordable product.”

WHO prequalification means the product can now be procured by the United Nations and financing agencies such as UNITAID, which has recently introduced hepatitis C in the portfolio of diseases it covers. Countries such as Indonesia, Vietnam, Cambodia, Myanmar, Mongolia, Nepal, Rwanda, Uganda, Kenya, Zambia, Ethiopia, Pakistan and Egypt are already procuring generic versions of sofosbuvir. The fact that WHO has prequalified one of those generics will give them extra guarantee of the product’s quality, safety and efficacy.

“Direct acting antiviral medicines such as sofosbuvir are highly effective for treating and curing chronic hepatitis C infection. But, at best, 1 out of 10 people in need had access to these medicines in 2015,” said Dr Gottfried Hirnschall, WHO’s Director of the HIV Department. “Prequalification of the hepatitis C medicine for the first-time is therefore exciting news, ahead of World Hepatitis Day next week.”

The average price of the required three-month treatment course of Mylan’s sofosbuvir is around US$ 260, a small fraction of the medicine’s market entry price in late 2013, and of the price set in the majority of high-income countries. The medicine remains highly expensive in many countries, but licensing agreements between Gilead Sciences, who developed sofosbuvir, and a number of generic manufacturers have made it possible for low-income and some middle-income countries to provide the medicine at more affordable prices.

HIV self-test
WHO today prequalified the first HIV self-test in a move to increase HIV diagnosis and treatment. The product, OraQuick ® HIV Self-Test (manufactured by OraSure Technologies Inc.) uses oral fluid as a specimen and provides results in as little as twenty minutes.

“The prequalification of this product means that countries with poor laboratory infrastructure will be able to safely increase testing capacity, thereby facilitating treatment of people living with HIV,” said Dr Suzanne Hill, Director, Essential Medicines and Health Products, WHO.

The move also marks a significant step in allowing countries to implement WHO guidelines, released in 2016, recommending HIV self-testing as a complementary approach to reach those who remain undiagnosed due to fear of stigma and discrimination.

“Over the past year, the number of countries incorporating HIV self-testing into their policies has increased from 16 to 40. This is impressive progress,” said Dr Gottfried Hirnschall, WHO’s Director of the HIV Department. “Having quality-assured self-tests is essential to enable countries to implement more rapidly. It is a positive step towards making innovative HIV self-testing accessible to all those who would benefit from it.”

In 2016, an estimated 30% of all people living with HIV remained unaware of their HIV status, many from higher risk populations who are either less likely to approach a health facility or are unable to do so.

“As the first HIV self-testing product to obtain WHO prequalification, this is a major step that will help give governments the confidence they need to adopt and scale up use of self-testing,” said Philippe Duneton, Deputy Executive Director of Unitaid.

There is currently great interest from the international community in deploying tests intended for HIV self-testing, with numerous countries having developed national guidelines and plans for implementation. Support for procurement and deployment of these tests has been pledged by most major international financing and procurement agencies, including a specific agreement on affordable pricing for 50 lower-middle income countries in Africa and Asia between the manufacturer and the Bill and Melinda Gates Foundation, a funder of WHO Prequalification.

http://www.who.int/medicines/news/2017/1st_generic-hepC_1stHIVself-test-prequalified/en/

Towards supporting greater and lower cost access to direct acting antiviral treatment for hepatitis C for all patients

Saudi J Gastroenterol [serial online] 2017 [cited 2017 Jul 20];23:263-4. Available from: http://www.saudijgastro.com/text.asp?2017/23/4/263/210834

LETTER TO EDITOR
Towards supporting greater and lower cost access to direct acting antiviral treatment for hepatitis C for all patients

Said A Al-Busafi1, Heba Omar2

Sir, It is with great interest that we read the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) position statement [1] and guidelines [2] on direct-acting antiviral agents (DAAs) for the treatment of hepatitis C virus (HCV) infection. The position statement and the guidelines, which were clearly influenced by the limited availability of highly priced DAAs, recommend that HCV treatment should be prioritized to patients at higher risk for developing HCV-related complications. The introduction of the curative DAAs to the global market caused worldwide celebration because it is expected to save millions of lives and control if not eliminate one of the major infectious disease worldwide.[3] Unfortunately, for the majority of HCV patients, these costly medications are not readily available, accessible, or affordable even for those in the developed countries.[3] This is likely going to affect many countries in their ability to minimize the burden of this disease.[4] On the other hand, generic DAAs (sofosbuvir, ledipasvir, and daclatasvir) are being produced in India and other countries with permission of the concerned pharmaceutical agencies and priced less than 1% of their current actual price in USA and Europe. The evidence for the clinical safety and efficacy of these generics is compelling including the recent interim results from international REDEMPTION trial presented by Freeman et al.[5] The results of this trial, which was supported by the European Association for the Study of the Liver (EASL), are important in indicating that generic DAAs are highly effective and safe comparable to those reported in clinical trials of branded DAAs. Another abstract presented by Hill et al. at the same meeting showed that the active pharmaceutical ingredient for the combination of sofosbuvir and daclatasvir was approximately $200 for 12 weeks' course of treatment per patient.[6] Oman, with an estimated HCV prevalence of 1%, is one such country where access to those important agents is also limited.[7] This has led many of our patients to self-import these drugs from India giving them hope instead of waiting for years to be treated from this debilitating disease. At the Sultan Qaboos University Hospital, using the EASL 2016 guidelines,[8] we have treated 58 HCV patients [28% genotype 3, 26% cirrhotic with 40% of them decompensated, and 3% severe chronic kidney disease (CKD)] with generic DAAs including (sofosbuvir, ledipasvir, and daclatasvir). Sustained virological response was achieved in 57 patients (98%), the remaining one patient with severe CKD discontinued treatment due to worsening renal function. All patients with decompensated cirrhosis were delisted from transplantation. Therefore, healthcare leaders and policy makers at the national and international level should adopt strategies to ensure that these DAAs are made available and are accessible and affordable for all in need. Download PDF Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.    References 1. Alghamdi AS, Alqutub A, Abaalkhail F, Sanai FM, Alghamdi H, Altraif I, et al. SASLT position statement on the direct-acting antiviral agents for the treatment of hepatitis C virus infection. Saudi J Gastroenterol 2015;21:60-3. [PUBMED]  [Full text]   2. Alghamdi AS, Alghamdi M, Sanai FM, Alghamdi H, Aba-Alkhail F, Alswat K, et al. SASLT Guidelines: Update in Treatment of Hepatitis C Virus Infection. Saudi J Gastroenterol 2016;22(Suppl 2):S25-S57.      3. Freeman JA, Hill A. The use of generic medications for hepatitis C. Liver Int 2016;36:929-32.      4. Edwards DJ, Coppens DG, Prasad TL, Rook LA, Iyer JK. Access to hepatitis C medicine. Bull World Health Organ 2015;93:799-805.      5. Freeman J, Sallie R, Kennedy A, Hieu PT, Jeffreys G, Hill AM. High sustained virological response rates using generic Direct Acting Antiviral treatment for Hepatitis C, imported into Australia. J Hepatol 2016;2:S209.      6. Hill A, Gotham D, Fortunak J. Significant Reductions in Costs of Generic Production of Sofosbuvir and Daclatasvir for Hepatitis C Treatment in Low- and Middle-Income Countries. J Hepatol 2016;2:S209.      7. Alnaqdy A, Alfahdi A, Alkobaisi M, Kaminski GZ. Prevalence of autoantibodies in patients with hepatitis C virus infection in Oman. Ann Saudi Med 2003;23:127-31.      8. European Association of the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2016. J Hepatol 2017;66:153-94.

Treatment with generic ledipasvir-sofosbuvir for 8 to 12 weeks was affective in Chinese patients with HCV genotype 1b

In the Journals
Generic ledipasvir-sofosbuvir achieved SVR12 in HCV genotype 1b
May 23, 2017
Healio
Treatment with generic ledipasvir-sofosbuvir for 8 to 12 weeks was affective in Chinese patients with hepatitis C genotype 1b, according to a recently published study.

“Genotype 1 is the most common in China, as it accounts for 58.4% of all HCV-infected persons, principally genotype 1b,” the researchers wrote. “As an eliminator of HCV and a leader of direct-acting antiviral agents (DAAs), sofosbuvir has revolutionized the treatment of [chronic hepatitis C] since 2013. However, brand name DAAs are unaffordable. Fortunately, Gilead Sciences ... approved generic ledipasvir-sofosbuvir with a very low price in many neighboring countries of China, and patients can go to these countries to purchase the drug and for treatment.”

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Of Interest
The controversy over expensive new drugs for hepatitis C
Link to research and news articles addressing the high cost of hepatitis C drugs; insurance restrictions - private insurers/Medicaid - and availability of generic versions/India, Egypt and other lower-income countries or through online "buyers clubs"

Costs for generic hepatitis C drugs available in India would be paid back in 5 to 10 years

PLOS ONE
Published: May 17, 2017
https://doi.org/10.1371/journal.pone.0176503
Full Text Article
Cost-effectiveness of hepatitis C treatment using generic direct-acting antivirals available in India
Treatment with generic DAAs available in India will improve patient outcomes, provide a good value for money within 2 years, and be ultimately cost-saving. Therefore, in this and similar settings, HCV treatment should be a priority from a public health as well an economic perspective.

Media Coverage Of This Article:
Costs for generic hepatitis C drugs available in India would be paid back in 5 to 10 years
May 17, 2017
Use of the generic versions of directly-acting antiviral (DAA) drugs that are available in India to treat hepatitis C virus (HCV) infection is not only cost effective but actually saves lifetime costs for treating infected patients in that country. A report from an international research team appears in the open-access journal PLOS ONE and describes finding that the upfront costs of DAA are offset by the avoidance of costs incurred to treat late-stage disease.

"More than 9 million people are infected with HCV in India, and more than 70 million worldwide," says Jagpreet Chhatwal, PhD, of the Institute for Technology Assessment at Massachusetts General Hospital (MGH), senior and corresponding author of the paper. "These persons are at risk of developing serious conditions such as cirrhosis and liver cancer, which can be fatal. However, only a fraction of them have been treated with these drugs so far."

First introduced in 2011, DAAs such as sofosbuvir (Sovaldi) and ledipasvir (which is combined with sofosbuvir in Harvoni) have proven to be remarkably successful in the battle against HCV infection, with cure rates exceeding 95 percent. In developed countries, treatment with DAAs is very expensive—reaching nearly $65,000 in the U.S.—although it meets standards for cost effectiveness. In those countries the advent of these drugs has drastically changed the landscape of HCV infection. But other countries have lagged behind in their use.

Through agreements with the pharmaceutical companies that developed these drugs, generic drug manufacturers in India are now able to produce versions that cost as little as $300 for the entire duration of treatment. But the absence of data on the cost effectiveness of these drugs in that country and low budgets for HCV treatment have meant that only a small proportion of people needing these drugs have received them.

The research team—including investigators from Sanjay Gandhi Postgraduate Institute of Medical Sciences in Lucknow, India, and the World Health Organization - used a mathematical model to compare the outcomes of DAA treatment with those of no DAA treatment based on profiles of 30 hypothetical patients with characteristics typical of Indian patients with HCV infection. Factors incorporated into the model included the natural history of HCV disease, the costs of DAA administration, the costs of treating the adverse outcomes of HCV disease, and quality of life of individuals infected with HCV.

The model indicated that, compared with no DAA treatment, use of the generic drugs in HCV-infected Indian patients would increase life expectancy by more than eight years while reducing lifetime health care costs by more than $1,300 per person. Payback for the upfront costs of DAA drugs would be achieved in an overall average of less than 10 years - under 5 years for patients at advanced stages of HCV disease and almost 12 years if treatment begins at earlier stages. Even though there was wide variation in the factors—such as patient age, disease stage, and viral genotype - input to the model, results always indicated that generic DAA treatment reduced lifetime costs.

"Our hypothesis was that treatment would be cost saving, given the low drug costs in India. However, we were pleasantly surprised to find that the full payback was achieved so soon after treatment," says Chhatwal, who is an assistant professor of Radiology at Harvard Medical School. "Our finding that treatment pays back its initial costs makes a very strong statement - that investment in HCV screening and treatment should be a priority for public health agencies in India and other countries where generic DAAs are available. It could also be argued that generic DAAs should be made available in other low- and middle-income countries where HCV infection is common and budgets for treatment limited."

Lead author Rakesh Aggarwal, MD, DM, of the Department of Gastroenterology at Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), a WHO Collaborating Center on Viral Hepatitis, says, "This is a win-win situation for the low- and low-middle-income countries where the generic DAAs can be sold. If these countries spend money on HCV treatment today, they will recoup it in the form of reduced health care expenditure within less than one decade. There is hardly any other health care intervention with such good return. Our results should show political leaders in those countries that they have a wonderful opportunity to make a difference for their constituents."

Read more at: https://medicalxpress.com/news/2017-05-hepatitis-drugs-india-paid-years.html#jCp

Sofosbuvir - WHO prequalifies first generic active ingredient for hepatitis C medicines

WHO prequalifies first generic active ingredient for hepatitis C medicines

On 31 March 2017, WHO for the first time prequalified a generic active pharmaceutical ingredient (API) for hepatitis C – sofosbuvir. Sofosbuvir is an essential ingredient for new, highly effective medicines to treat hepatitis C called direct active antivirals (DAAs). The prequalified product’s manufacturer is Mylan Laboratories Ltd - INDIA.

The emergence of DAAs in 2014 gave new hope to the 80-110 million people suffering from chronic hepatitis C, a disease that attacks the liver and kills approximately 700 000 people each year. The new medicines have an average 90% cure rate, have fewer side effects than previously available therapies and treatment regimens generally last just twelve weeks against the many months required with the older medicines. But these products are priced prohibitively, even for health systems in high-income countries.

Through a series of pricing strategies, including sub-licensing agreements, generic competition and price negotiations, some countries are making progress in tackling the disease. However, high-income and upper-middle-income countries are excluded from some of these arrangements and are often forced to ration treatment by making it available only for the sickest patients. To date, many of the people who need treatment before the virus causes permanent and often lethal liver damage are not accessing it.

By prequalifying the API, WHO has identified a quality source for generic manufacturers who wish to produce sofosbuvir. This should increase the availability of affordable generic medicines, thereby contributing to increased patient access. For example, generic competition has so far reduced prices in a number of countries: a three-month course of treatment in Egypt dropped from US$ 900 in 2015 to less than US$ 200 in 2016, and in Pakistan the same course today costs as little as
US$ 100.

http://www.who.int/medicines/news/2017/1st_generic-hepCprequalified_active_ingredient/en/?platform=hootsuite

Generic ledipasvir-sofosbuvir for patients with chronic hepatitis C: a real-life observational study

Journal of Hepatology

Lay summary
The expensiveness of Harvoni® led to restrictions and access limitations in many developing and even developed countries with limited healthcare budgets. Gilead approved generic ledipasvir-sofosbuvir costs far less than Harvoni® and presents similar cure rate for patients with chronic hepatitis C.

Generic ledipasvir-sofosbuvir for patients with chronic hepatitis C: a real-life observational study
Qing-Lei Zeng , Guang-Hua Xu†, Ji-Yuan Zhang†, Wei Li†, Da-Wei Zhang, Zhi-Qin Li, Hong-Xia Liang, Chun-Xia Li, Zu-Jiang Yu

Abstract

Background & aims
Few patients from developing countries can afford brand name direct-acting antiviral agents for treatment of hepatitis C virus (HCV) infection, and controversy regarding the bioequivalence of generics exists. This study aimed to observe the safety and efficacy of 8 or 12 weeks of generic ledipasvir-sofosbuvir with or without ribavirin for Chinese genotype 1b HCV-infected patients.

Methods
In this open-labelled observational study, 63 cirrhotic (group 1) and 65 non-cirrhotic (group 2) patients were administered generic ledipasvir-sofosbuvir plus 1,000-1,200 mg of ribavirin daily for 12 and 8 weeks, respectively; and 64 non-cirrhotic patients (group 3) received ledipasvir-sofosbuvir for 8 weeks. The primary efficacy endpoint was undetectable HCV RNA at week 12 (SVR12) after cessation of therapy. Safety and pharmacokinetic data were collected.

Results
One hundred and eighty-seven patients completed treatment, and the latest undetectable HCV RNA was observed in three cirrhotic patient at week 5 during treatment. Intention-to-treat analysis revealed 96.8% (61/63), 96.9% (63/65), and 96.9% (62/64) of SVR12 rates in groups 1, 2, and 3, respectively. One patient in group 3 relapsed at post-treatment week 4. The regimens were generally well-tolerated. The most common adverse events were fatigue (17.8%), diarrhea (10.9%), and headache (9.9%). Four patients discontinued therapy due to diarrhea and vomiting. One patient from group 2 discontinued treatment on day 29 because of drug-unaffordability; fortunately, she achieved SVR12.

Conclusion
This study first demonstrated that 8 or 12 weeks of generic ledipasvir-sofosbuvir with or without ribavirin are safe and effective for patients with genotype 1b HCV infection.

DOI: http://dx.doi.org/10.1016/j.jhep.2017.01.025

Of Interest
Link To Articles On This Blog -  HCV Generics

AASLD 2016
Generic sofosbuvir-based therapy under performs in real-world setting, but is use of suboptimal regimens the reason?
Michael Carter
Published:09 December 2016
Generic sofosbuvir-based combinations may not perform as well as therapy based on branded sofosbuvir-containing regimens, according to result of a study conducted in Qatar and presented to the recent 2016 AASLD Liver Meeting. People treated with generics were less likely to have a sustained virological response 12-weeks post treatment (SVR12) and were also more likely to experience an adverse event, compared to people who received branded drugs.
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Generic Sofosbuvir Underperforms in Real World, May Be Due to Suboptimal Regimens

AASLD 2016: Generic Sofosbuvir Underperforms in Real World, May Be Due to Suboptimal Regimens

HCV Treatment Published on Thursday, 15 December 2016

Written by Michael Carter

Generic sofosbuvir-based combinations for hepatitis C may not perform as well as branded sofosbuvir-containing regimens, according to a study conducted in Qatar and presented at the recent 2016 AASLD Liver Meeting. People treated with generics were less likely to be cured and more likely to experience adverse events compared to people who received branded drugs. But the investigators speculate that the generics may have underperformed because many people treated were with suboptimal regimens, and believe this deserves further research.

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