Showing posts with label Epclusa® (Sofosbuvir/Velpatasvir). Show all posts
Showing posts with label Epclusa® (Sofosbuvir/Velpatasvir). Show all posts

Thursday, November 29, 2018

Ribavirin Beneficial For Patients with Hepatitis C Genotype 3

Ribavirin Beneficial For Patients with Hepatitis C Genotype 3
NOVEMBER 29, 2018
Kenneth Bender, PharmD, MA

The addition of ribavirin to a regimen of sofosbuvir and velpatasvir (Epclusa) to treat hepatitis C virus (HCV) genotype 3 appeared to increase efficacy for patients with compensated cirrhosis, particularly in those with resistance-associated substitution (RAS), in a trial that sought to confirm the therapeutic strategy for this considered difficult-to-cure population.

Rafael Esteban, MD, of the Vall d'Hebron Hospital University, Spain, and colleagues conducted the comparison in patients with compensated cirrhosis to elaborate on earlier indications of ribavirin benefit from phase 2 studies, and from the ASTRA-4 study in patients with HCV genotype 3 and decompensated cirrhosis.
Read more:
https://www.mdmag.com/medical-news/ribavirin-beneficial-for-patients-with-hepatitis-c-genotype-3

Recommended Reading
The Liver Meeting
San Francisco
November 2018

On This Blog
Review research articles with a focus on treating HCV according to genotype using FDA approved  medicines. Information is extracted from news articles, peer-reviewed journals, as well as liver meetings/conferences, research manuscripts and interactive learning activities.

Friday, November 9, 2018

Gilead Presents Latest Data from Viral Hepatitis Research Programs at The Liver Meeting® 2018

November 09, 2018

– Data Demonstrate Sofosbuvir-Based Regimens Achieve High Cure Rates in Hepatitis C Patient Populations with Unmet Need –
– Early Data from Gilead’s Functional Hepatitis B Cure Program Suggest Activation of Immune Cells Crucial to Viral Clearance –
SAN FRANCISCO--(BUSINESS WIRE)--Nov. 9, 2018-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from studies investigating Epclusa® (sofosbuvir 400mg/velpatasvir 100mg) in chronic hepatitis C virus (HCV) infected patients with severe renal impairment undergoing dialysis and Harvoni® (ledipasvir/sofosbuvir) in pediatric HCV patients aged three to five years, adding to the efficacy and safety profile of sofosbuvir-based regimens across diverse patient populations. These results, along with data from Gilead’s hepatitis B virus (HBV) cure development program, are being presented at The Liver Meeting® 2018 in San Francisco this week.
“Our scientific leadership has helped transform the treatment of patients with chronic hepatitis C infection and we remain committed to ensuring effective and well-tolerated treatment options for a broad range of patient populations.” said John McHutchison, AO, MD, Chief Scientific Officer, Head of Research and Development, Gilead Sciences. “For patients with chronic hepatitis B infection, we are intensifying our efforts to advance research and development toward a functional cure.”
Further Progress in the Treatment of Hepatitis C
Results from an open-label Phase 2 study demonstrated that treatment with the once-daily single-tablet regimen of Epclusa for 12 weeks in patients with genotype 1, 2, 3, 4 or 6 HCV and severe renal impairment undergoing dialysis resulted in cure rates (SVR12, or undetectable viral load 12 weeks after completion of therapy) of 95 percent (n=56/59) with only two patients experiencing virologic failure. The most common adverse events (AEs) (>10 percent) were headache, fatigue, nausea, vomiting and insomnia. No patients discontinued therapy due to an adverse event.
In another open-label Phase 2 study, children aged three to five years old with genotype 1 or 4 HCV infection received weight-based oral dosing of ledipasvir/sofosbuvir granules 33.75 mg/150 mg if < 17 kg or 45 mg/ 200 mg if ≥ 17 kg) once-daily for 12 weeks. Overall, 97 percent (n=33/34) of the patients were cured, and none experienced virologic failure. The most common AEs (>10 percent) were vomiting, cough, pyrexia, rhinorrhea and streptococcal pharyngitis. One patient discontinued treatment due to an adverse event of abnormal drug taste.
The use of Epclusa and Harvoni, including granules formulation, in the aforementioned patient populations is investigational; their safety and efficacy have not been established. The granule formulation is not approved. Epclusa and Harvoni are both indicated in the US for the treatment of chronic HCV infection in patients with no cirrhosis or compensated cirrhosis: Epclusa for adults with genotypes 1-6; and Harvoni for patients 12 years and older (or ≥35 kg) with genotypes 1, 4, 5 and 6. The US product labels for Epclusa and Harvoni each contain a Boxed Warning for the risk of hepatitis B reactivation in HCV/HBV co-infected patients. See below for US Important Safety Information.
Hepatitis B Cure Research
Gilead is presenting data on GS-9688, an investigational, oral selective toll-like receptor 8 (TLR8) agonist, one of several compounds under investigation as part of Gilead’s HBV cure program. The data support continued development of GS-9688 as a potential therapeutic approach for achieving a functional cure for patients with chronic HBV infection.
In the first-in-human, healthy volunteer safety study, GS-9688 was well-tolerated at single ascending doses up to 5mg and resulted in pharmacodynamic activity as demonstrated by the production of the systemic cytokines IL-1RA and IL-12p40 and by the activation of key relevant immune cells including natural killer (NK) cells and mucosal-associated invariant T (MAIT) cells. The most commonly reported AEs among people receiving doses up to and including 5 mg were nausea and vomiting. There were no reports of Grade 3 or higher AEs, laboratory AEs or serious adverse events (SAEs) and no discontinuations or deaths.
In a Phase 1b safety and tolerability study of GS-9688 in HBV chronically infected patients, dose-dependent activation of the cytokines IL-12p40 and IL-1RA was demonstrated with once weekly dosing for up to 4 weeks in viremic and virally-suppressed patients. There were no reports of SAEs; the most common AEs were headache and nausea. Based on these data, GS-9688 is currently being evaluated in Phase 2 studies in patients with chronic hepatitis B.
GS-9688 is an investigational agent and not approved; its safety and efficacy have not been established.
Latest Research in Hepatitis B Treatment
Presentations on Vemlidy® (tenofovir alafenamide 25mg, TAF) add further evidence to its established safety and efficacy profile in adults with chronic HBV and compensated liver disease, including longer term data on the safety of Vemlidy in virologically suppressed HBV patients. Through three years of treatment, patients originally randomized to receive TAF continued to show an improved bone and renal safety profile compared to treatment with tenofovir disoproxil fumarate 300mg (TDF) with maintained viral suppression. In a separate study in post-liver transplant patients virally suppressed on TDF-based regimens, switching to TAF maintained viral suppression in all TAF-treated patients with improvements in renal function and bone mineral density, after 48 weeks of treatment.
The use of Vemlidy in post-liver transplant patients is investigational; its safety and efficacy have not been established. Vemlidy is indicated in the US for the treatment of chronic HBV infection in adults with compensated liver disease. The US Prescribing Information for VEMLIDY contains a Boxed Warning regarding the risk of post treatment severe acute exacerbation of hepatitis B; see below for Important Safety Information.
US Important Safety Information About Epclusa and Harvoni
BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with EPCLUSA or HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
Warnings and Precautions
Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with EPCLUSA or HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir containing regimen. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
Risk of Reduced Therapeutic Effect Due to Use with P-gp Inducers and/or Moderate to Potent Inducers of CYP: Rifampin, St. John’s wort and carbamazepine are not recommended for use with EPCLUSA or with HARVONI. P-gp inducers may significantly decrease ledipasvir, sofosbuvir and/or velpatasvir plasma concentrations. Moderate to potent inducers of CYP2B6, CYP2C8 or CYP3A4 may significantly decrease sofosbuvir and/or velpatasvir plasma concentrations.
Adverse Reactions
The most common adverse reactions (≥10%, all grades) with EPCLUSA were headache and fatigue.
The most common adverse reactions (≥10%, all grades) with HARVONI were fatigue, headache, and asthenia.
Drug Interactions
EPCLUSA: Coadministration is not recommended with topotecan due to increased concentrations of topotecan; or with proton-pump inhibitors, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, efavirenz, and tipranavir/ritonavir due to decreased concentrations of sofosbuvir and/or velpatasvir.
HARVONI: Coadministration is not recommended with oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir due to decreased concentrations of ledipasvir and sofosbuvir; or with co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of tenofovir; or with simeprevir due to increased concentrations of ledipasvir and simeprevir; or with rosuvastatin due to increased concentrations of rosuvastatin.
Consult the full Prescribing Information for EPCLUSA and HARVONI for more information on potentially significant drug interactions, including clinical comments.
US Important Safety Information About Vemlidy
BOXED WARNING: POST TREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS B
Discontinuation of anti-hepatitis B therapy, including VEMLIDY, may result in severe acute exacerbations of hepatitis B. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VEMLIDY. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
Warnings and Precautions
Risk of Development of HIV-1 Resistance in HBV/HIV-1 Coinfected Patients: Due to this risk, VEMLIDY alone should not be used for the treatment of HIV-1 infection. Safety and efficacy of VEMLIDY have not been established in HBV/HIV-1 coinfected patients. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with VEMLIDY, and, if positive, an appropriate antiretroviral combination regimen that is recommended for HBV/HIV-1 coinfected patients should be used.
New Onset or Worsening Renal Impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of VEMLIDY, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue VEMLIDY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Monitor renal function in all patients – See Dosage and Administration.
Lactic Acidosis and Severe Hepatomegaly with Steatosis: Fatal cases have been reported with the use of nucleoside analogs, including tenofovir DF. Discontinue VEMLIDY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.
Adverse Reactions
Most common adverse reactions (incidence ≥5%; all grades) were headache, abdominal pain, cough, back pain, fatigue, nausea, arthralgia, diarrhea, and dyspepsia.
Drug Interactions
Coadministration of VEMLIDY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir and the risk of adverse reactions.
Coadministration of VEMLIDY is not recommended with the following: oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, or St. John’s wort. Such coadministration is expected to decrease the concentration of tenofovir alafenamide, reducing the therapeutic effect of VEMLIDY. Drugs that strongly affect P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) activity may lead to changes in VEMLIDY absorption.
Consult the full prescribing information for VEMLIDY for more information on potentially significant drug interactions, including clinical comments.
Dosage and Administration
Dosage: Adults; 1 tablet taken once daily with food.
Renal Impairment, Screening, and Monitoring: VEMLIDY is not recommended in patients with CrCl <15 mL/min. In all patients, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein prior to initiating and during treatment, on a clinically appropriate schedule. In patients with chronic kidney disease, also assess serum phosphorus.
Hepatic Impairment: Not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment.
Testing Prior to Initiation: HIV infection.

Thursday, September 27, 2018

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

Of Interest
October 29, 2018
Gilead $1,100 a day drug. Now it will launch a generic at quarter the price
Sep 27, 2018
An ‘unusual decision’: Gilead to launch hep C generics ten years early

Sept 26 2018
The U.S. drug pricing system is a mess. It's an absolute disaster. Just about every entity involved, from drug companies to consumers to insurers to the government, agrees that offering discounts off the list price is a convoluted way to sell a life-saving product.

Maria Carolina Marcello, Gram Slattery
A Brazilian court has stripped the patent protection of a Gilead Sciences Inc big-selling hepatitis C treatment in Brazil, paving the way for cheaper generics, a presidential candidate who pushed for the move said on Monday....

Gilead Sciences to Sell Authorized Generics of Hepatitis C Drugs
Gilead Sciences will sell authorized generics of its blockbuster hepatitis C drugs Epclusa and Harvoni, Bloomberg reported. The brand-name versions sparked widespread debate about US pharmaceutical costs when they were introduced at a price of more than $1000 per pill. The less expensive versions will cost $24,000 for a course of treatment, which compares with a list price for Harvoni of $94,500. The company’s hepatitis C drugs remain among the best-selling pharmaceutical products in history, but they've also made Gilead the subject of congressional hearings and accusations of greed.

Gilead Press Release
United States
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 --

FOSTER CITY, Calif.--(BUSINESS WIRE)--Sep. 24, 2018-- Gilead Sciences, Inc. (NASDAQ: GILD) announced today plans to launch authorized generic versions of Epclusa® (sofosbuvir 400mg/velpatasvir 100mg) and Harvoni® (ledipasvir 90mg/sofosbuvir 400mg), Gilead's leading treatments for chronic hepatitis C virus (HCV), in the United States, through a newly created subsidiary, Asegua Therapeutics LLC. The authorized generics will launch at a list price of $24,000 for the most common course of therapy and will be available in January 2019.

Since the launch of Gilead's first HCV medication in 2013, the average price paid for each bottle of medicine in the United States has decreased by more than 60 percent off of the public list prices, across health insurers and government payers. Due to the complexity and structure of the U.S. healthcare system, however, these discounts provided by Gilead may not always translate into lower costs for patients. Further, existing contracts, together with laws associated with government pricing policies, make it challenging to quickly lower a product's list price once it is on the market.

The authorized generics are priced to more closely reflect the discounts that health insurers and government payers receive today. Insurers will have the choice of offering either the authorized generics or the branded medications for both Epclusa and Harvoni. In the Medicare Part D setting, the authorized generics could save patients up to $2,500 in out-of-pocket costs per course of therapy. The authorized generics will also offer substantial savings to state managed Medicaid plans that do not currently benefit from negotiated rebates and that represent a significant number of people in need, potentially opening up access to our medications to beneficiaries who were previously denied coverage.

"Launching these authorized generics is the best solution available to us today to quickly introduce a lower-priced alternative to our HCV medications without significant disruption to the healthcare system and our business," said John F. Milligan, PhD, President and Chief Executive Officer, Gilead Sciences. "This launch also will hopefully help increase transparency by more closely aligning our medications' list prices with their cost. Our ultimate goal is to lower the list price of Epclusa - a medication we believe is of great importance given its clinical profile across genotypes - and Harvoni. We are committed to working with all of our partners in the healthcare system to help enable list price reductions of our HCV medications and find better solutions to reduce patients' out-of-pocket costs."

Beyond the company's efforts to reduce patient costs, Gilead is continuing to pursue innovative collaborations and long-term financing models, such as a potential subscription model, that could not only expand access, but aim to eliminate HCV in the United States and around the world.

About Gilead Sciences, Inc.
Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors that could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended June 30, 2018, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

Wednesday, September 12, 2018

Epclusa® (Sofosbuvir/Velpatasvir) with or without ribavirin in patients with decompensated cirrhosis

Journal of Gastroenterology - September 10, 2018 

Efficacy and safety of sofosbuvir–velpatasvir with or without ribavirin in HCV-infected Japanese patients with decompensated cirrhosis: an open-label phase 3 trial
Tetsuo Takehara Naoya Sakamoto Shuhei Nishiguchi Fusao IkedaTomohide TatsumiYoshiyuki UenoHiroshi Yatsuhashi Yasuhiro Takikawa Tatsuo Kanda Minoru Sakamoto Akihiro Tamori Eiji MitaKazuaki Chayama Gulan Zhang Shampa De-Oertel Hadas Dvory-SobolTakuma Matsuda Luisa M. Stamm Diana M. Brainard Yasuhito Tanaka Masayuki Kurosaki

Sofosbuvir –velpatasvir for 12 weeks provides a highly effective and well-tolerated therapy for Japanese patients with HCV and decompensated cirrhosis. Ribavirin did not improve efficacy but increased toxicity.

Open Access 
First Online: 10 September 2018
Full text article available online: 

Abstract
Background
In Japan, hepatitis C virus (HCV)-infected patients with decompensated cirrhosis currently have no treatment options. In this Phase 3 study, we evaluated sofosbuvir–velpatasvir with or without ribavirin for 12 weeks in patients with any HCV genotype and decompensated cirrhosis [Child–Pugh–Turcotte (CPT) class B or C] in Japan.

Methods
Patients were randomized 1:1 to receive sofosbuvir–velpatasvir with or without ribavirin for 12 weeks. Randomization was stratified by CPT class and genotype. Sustained virologic response 12 weeks following completion of treatment (SVR12) was the primary efficacy endpoint.

Results
Of the 102 patients enrolled, 57% were treatment naive, 78% and 20% had genotype 1 and 2 HCV infection, respectively, and 77% and 20% had CPT class B and C cirrhosis, respectively, at baseline. Overall, 61% of patients were female and the mean age was 66 years (range 41–83). SVR12 rates were 92% (47/51) in each group. Among patients who achieved SVR12, 26% had improved CPT class from baseline to posttreatment week 12. Most adverse events (AEs) were consistent with clinical sequelae of advanced liver disease or known toxicities of ribavirin. Four patients (8%) who received sofosbuvir–velpatasvir and seven (14%) who received sofosbuvir–velpatasvir plus ribavirin experienced a serious AE. The 3 deaths (bacterial sepsis, gastric varices hemorrhage, hepatocellular carcinoma) were attributed to liver disease progression.

Conclusion
Sofosbuvir–velpatasvir for 12 weeks provides a highly effective and well-tolerated therapy for Japanese patients with HCV and decompensated cirrhosis. Ribavirin did not improve efficacy but increased toxicity.

Thursday, June 21, 2018

Sofosbuvir/velpatasvir and Resistance-associated Substitutions in HCV genotype 3

SOF/VEL and Resistance-associated Substitutions in HCV GT3
Alimentary Pharmacology & Therapeutics, June 21, 2018
J. von Felden; J. Vermehren; P. Ingiliz; S. Mauss; T. Lutz; K. G. Simon; H. W. Busch; A. Baumgarten; K. Schewe; D. Hueppe; C. Boesecke; J. K. Rockstroh; M. Daeumer; N. Luebke; J. Timm; J. Schulze zur Wiesch; C. Sarrazin; S. Christensen

Does the presence of resistance-associated substitutions impact the efficacy of therapy with sofosbuvir/velpatasvir with or without ribavirin in patients with HCV genotype 3?
Medscape - Full Text

Abstract and Introduction
Abstract
Background Twelve weeks of the pangenotypic direct–acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL–3 approval study. However, presence of resistance–associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response.

Aim To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real–world setting.

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Tuesday, June 5, 2018

Cost‐effectiveness of generic sofosbuvir/velpatasvir versus genotype‐dependent direct‐acting antivirals for hepatitis C treatment

In Case You Missed It
*Article downloaded and shared by @HenryEChang via Twitter. 

Cost‐effectiveness of generic pan‐genotypic sofosbuvir/velpatasvir versus genotype‐dependent direct‐acting antivirals for hepatitis C treatment
Amit Goel Qiushi Chen Jagpreet Chhatwal Rakesh Aggarwal
First published: 04 June 2018 https://doi.org/10.1111/jgh.14301

Download Full-Text
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Abstract
Background
Treatment of HCV infection with low‐cost generic direct‐acting antivirals (DAAs) available in India and other developing countries needs determination of HCV genotype (‘genotype‐dependent' regimens). Generic velpatasvir, a DAA that obviates the need for genotype determination (‘pan‐genotypic' regimen) recently became available but is costlier.

Aim
To evaluate the cost‐effectiveness of genotype‐dependent versus pan‐genotypic DAA treatments in India.

Methods
A previously‐validated microsimulation model, adapted to Indian population, was used to compare the costs and long‐term outcomes of three scenarios: no treatment, and treatment with genotype‐dependent and pan‐genotypic regimens. Input parameters were derived from literature. Using a payer's perspective and life‐time time horizon, quality‐adjusted life years (QALYs), total costs, and incremental cost‐effectiveness ratio (ICER) were calculated. Both deterministic and probabilistic sensitivity analyses were also conducted.

Results
At the current price (US$ 223 for 4 weeks), pan‐genotypic regimen was cost‐saving compared to no treatment. Compared with genotype‐dependent regimens, it increased QALYs by 0.92 and increased costs by US$ 107, but was deemed cost‐effective with an ICER of US$ 242 per QALY gained. Probabilistic sensitivity analysis also supported the cost‐effectiveness of pan‐genotypic regimen. At the reduced price of US$ 188 for 4 weeks, the pan‐genotypic regimen will become cost‐neutral to genotype‐dependent regimens (current price: US$100 for 4 weeks).

Conclusions
At current prices, velpatasvir‐based pan‐genotypic regimen is cost‐effective for HCV treatment in India where generic drugs are available. A reduction in the prices of pan‐genotypic regimen has the potential to make its use cost‐saving, while simplifying treatment in community‐level programs aimed at HCV elimination.
Continue reading:
https://jumpshare.com/v/AGnldst6EL08X8iGM13N

Available 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"

Wednesday, May 30, 2018

China Drug Administration Approves Epclusa® (Sofosbuvir/Velpatasvir)

China Drug Administration Approves Epclusa® (Sofosbuvir/Velpatasvir), Gilead's Pan-Genotypic Treatment for Chronic Hepatitis C Virus Infection

- Epclusa is the First Approved Pan-Genotypic Once Daily Single Table Regimen for Chronic Hepatitis C Virus Infection in China -

FOSTER CITY, Calif.--(BUSINESS WIRE)--May 30, 2018-- Gilead Sciences, Inc. (NASDAQ: GILD) announced today that the China Drug Administration (CDA) has approved Epclusa® (sofosbuvir 400 mg/velpatasvir 100 mg) for the treatment of adults with genotype 1-6 chronic hepatitis C virus (HCV) infection. The CDA also approved Epclusa in combination with ribavirin (RBV) for adults with HCV and decompensated cirrhosis. Epclusa is the first pan-genotypic HCV single tablet regimen (STR) approved in China.

The approval of Epclusa in China is supported by five international Phase 3 studies, ASTRAL-1, ASTRAL-2, ASTRAL-3, ASTRAL-4 and ASTRAL-5. High overall rates of SVR12 (defined as undetectable HCV RNA 12 weeks after completing therapy), ranging from 92-100 percent, were achieved across difficult-to-cure patient populations including treatment-experienced patients and those with compensated or decompensated cirrhosis.

"The safety and efficacy profile of Epclusa are supported by large clinical and real-world global datasets," said Professor Lai Wei, Peking University People's Hospital and Institute of Hepatology, Peking University. "With high cure rates across all HCV genotypes, Epclusa could increase HCV treatment in China by potentially eliminating the need for genotype testing, which can be a barrier to treatment in many settings."

HCV is the fourth-most commonly reported infectious disease in China, with approximately 10 million people infected. HCV genotypes 1, 2, 3 and 6 account for more than 96 percent of all cases.

In the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,035 treatment-naïve and treatment-experienced patients with genotype 1-6 HCV infection, without cirrhosis or with compensated cirrhosis, received 12 weeks of Epclusa. Ninety-eight percent (1,015/1,035) of patients achieved SVR12. In the ASTRAL-5 study, 106 treatment-naïve and treatment-experienced patients with genotype 1-6 HCV infection, without cirrhosis or with compensated cirrhosis, who were coinfected with HIV and on a stable antiretroviral therapy, received 12 weeks of Epclusa. Ninety-five percent (101/106) of patients achieved SVR12.

The ASTRAL-4 study assessed the safety and efficacy of 12 weeks of Epclusa with or without RBV or 24 weeks of Epclusa in 267 HCV-infected patients with genotypes 1-4 and 6 decompensated cirrhosis (Child-Pugh B). Patients with decompensated cirrhosis receiving Epclusa with RBV for 12 weeks achieved 94 percent (82/87) SVR12.

The most common adverse reactions (=10 percent) experienced by patients treated with Epclusa in ASTRAL-1, ASTRAL-2, ASTRAL-3 and ASTRAL-5 were headache and fatigue. The placebo-treated patients in the ASTRAL-1 experienced headache and fatigue at a similar frequency. The most common adverse reactions (=10 percent) experienced by HCV-infected patients with decompensated cirrhosis treated with Epclusa and RBV in ASTRAL-4 were fatigue, anemia, nausea, headache, diarrhea and insomnia. Four patients treated with Epclusa with RBV, discontinued treatment due to adverse events.

"As the first once-daily, interferon-free single tablet regimen for HCV patients regardless of genotype, Epclusa offers physicians in China an important new option for effectively treating their patients while potentially helping to reduce the significant burden of HCV at a population level," said John F. Milligan, PhD, Gilead's President and Chief Executive Officer. "Gilead has now launched two direct-acting antiviral treatments in China, and we are committed to supporting efforts to screen and link patients to treatment, to help address the country's HCV epidemic."

Epclusa received marketing approval from the U.S. Food and Drug Administration (FDA) and the European Commission in 2016 as the first pan-genotypic STR for HCV infection. It is also approved for use in 54 countries.

Sovaldi (sofosbuvir) as a single agent received marketing approval from the China Food and Drug Administration in 2017 for the treatment of adults infected with HCV genotype 1, 2, 3, 4, 5 or 6 and for adolescents (aged 12 to 18 years) with HCV genotype 2 or 3, as a component of a combination antiviral treatment regimen.

Friday, April 13, 2018

Eight weeks of treatment with Epclusa cured almost all people receiving opioid substitution therapy

Conference news @infohep
Eight weeks of treatment with Epclusa cured almost all people receiving opioid substitution therapy
Keith Alcorn
Published: 12 April 2018
An eight-week course of sofosbuvir/velpatasvir (Epclusa) cured almost all people with hepatitis C genotype 3 without cirrhosis receiving treatment alongside opioid substitution therapy through community pharmacies or prisons in the Greater Glasgow area, Alison Boyle of Gartnavel Hospital, Glasgow, reported at the 2018 International Liver Congress in Paris on Thursday. Genotype 3 is especially common in people who inject drugs and former drug users. It has been considered 'harder to cure' although recent studies of newer agents in people with genotype 3 have shown high cure rates.
Continue reading......

Slides @ NATAP
8 weeks sofosbuvir/velpatasvir in genotype 3 patients with significant fibrosis: Highly effective amongst an OST cohort - (04/13/18)

New @infohep
New Hepatocellular carcinoma (HCC)
EASL updates liver cancer guidelines at International Liver Congress
Liz Highleyman / 7 hours ago
The European Association for the Study of the Liver (EASL) presented updated clinical practice guidelines for the management of hepatocellular carcinoma (HCC) during a special session at the 2018 International Liver Congress yesterday

New NAFLD
Cenicriviroc treatment improves liver fibrosis in people with NASH
Liz Highleyman / 7 hours ago
Cenicriviroc, a drug that blocks both CCR5 and CCR2 receptors on immune cells, continued to show an anti-fibrotic effect in people with non-alcoholic steatosis (NASH) after two years of follow-up, according to a

New Treatment for people who use drugs
Eight weeks of treatment with Epclusa cured almost all people with HCV receiving opioid substitution therapy
Keith Alcorn / 18 hours ago
An eight-week course of sofosbuvir/velpatasvir (Epclusa) cured almost all people with hepatitis C genotype 3 without cirrhosis receiving treatment alongside opioid substitution therapy through community pharmacies or prisons in the Greater Glasgow area...

Pan-genotypic regimens
New affordable hepatitis C combination shows 97% cure rate
Keith Alcorn / 12 April 2018
The combination of sofosbuvir and the new NS5A inhibitor ravidasvir cured 97% of people with hepatitis C in a study carried out in Malaysia, and could provide a safe and

Thursday, April 12, 2018

Liver Congress 2018 - ‘what you need to know in 5-minutes’ video clips each day from the conference

 ‘what you need to know in 5-minutes’

Hi folks, if you need help navigating the International Liver Congress, begin here: For Patients: The International Liver Congress 2018 . This page is a collection of links with conference updates and a list of websites you may be interested in visiting. As once a patient myself, exploring Practice Point was an easy way to review key data presented at the meeting.  Each day of the conference Practice Point uploads 5-minute video clips summarizing that day's hepatitis C presentations. However, you need to register, its free, check out the process below with highlights of today's clip. 

Link: Practice Point
Independent Conference Coverage from the 53rd Annual Congress of the European Association for the Study of the Liver (EASL)*
In this video series, Dr. Brown will present ‘what you need to know in 5‐minutes’ regarding today's presentations from The International Liver Congress EASL 2018 in Paris, France. These educational Clinical Clips will spotlight the latest advances in the prevention and treatment of hepatitis C through a series of daily, ‘what you need to know in 5-minutes’ videos each day from the conference. 

Clinical Clips Day One - April 12, 2018
Highlights: Harvoni® (Ledipasvir/Sofosbuvir) 8wks treatment vs 12wks in black treatment-naïve genotype 1 patients.

HCV genotype 3 using 8wks of Epclusa® (Sofosbuvir/Velpatasvir) for patients on Opioid Substitution therapy.

Epclusa® (Sofosbuvir/Velpatasvir) plus ribavirin for HCV genotype 3 patients with cirrhosis, and finally HCV treatment for patients with decompensated cirrhosis.
Start here.....

Check Practice Point each day of the conference, April-12 - April 15.

For patients, navigating registration
Link - Click here to register
The good news, only areas marked with * are required. The process is self-explanatory, it goes like this.

Email *
Confirm Email *
Password * Confirm Password *
First Name *
Last Name *
Degree * If you do not have a medical degree type in "Other" when the next box appears, type in "Patient"
Select the category that best represents your specialty * Pick one, anyone.
Areas of Interest (Check all that apply) * Pick one, anyone.

Good luck

Thursday, March 29, 2018

Hepatitis C genotype 3 - 12 weeks of SOF/VEL safe and highly efficient across a diverse patient population

In conclusion, we confirm an overall very high efficacy and safety of 12 weeks of SOF/VEL in patients with HCV GT3 infection in a real-world setting. While the prevalence of clinically relevant NS5A RASs was low, our data indicate that their impact may be of less importance than previously expected. Thus, addition of RBV may only be required in certain subgroups, including patients with previous DAA-experience and/or decompensated cirrhosis.

Alimentary Pharmacology and Therapeutics
High efficacy of sofosbuvir/velpatasvir and impact of baseline resistance‐associated substitutions in hepatitis C genotype 3 infection
J. von Felden J. Vermehren P. Ingiliz S. Mauss T. Lutz K. G. Simon H. W. Busch A. Baumgarten K. Schewe D. Hueppe C. Boesecke J. K. Rockstroh M. Daeumer N. Luebke ...

First published: 14 March 2018 https://doi.org/10.1111/apt.14592

Full-Text Article
View Online
Download PDF

Summary Background
Twelve weeks of the pangenotypic direct‐acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL‐3 approval study. However, presence of resistance‐associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response.

Aim
To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real‐world setting.

Methods
In this multicentre cohort study, GT3 patients from ten treatment centres across Germany were included. Sustained virological response was assessed 12 weeks after end‐of‐treatment (SVR12) in modified intention‐to‐treat (mITT) and per‐protocol analysis (PP). NS5A RASs were tested by population‐based sequencing.

Results
A total of 293 GT3 patients were included. The median age was 48 years, 70% were male, 25.3% were cirrhotic, 9.2% were HCV/HIV co‐infected and 21.8% were treatment‐experienced, including 4.1% with DAA experience. Baseline NS5A RASs (Y93H, A30K, L31M) were detected in 11.2%. RBV was added in 5% of noncirrhotic and 58.9% of cirrhotic patients, respectively. SVR12 rates for SOF/VEL±RBV were 95.9% (mITT) and 99.5% (PP), respectively. Only 1 virological relapse occurred in a cirrhotic patient previously treated with SOF/RBV. No treatment‐related major adverse events occurred.

Conclusion
Twelve weeks of SOL/VEL±RBV was safe and highly efficient in HCV GT3 across a diverse patient population. Baseline NS5A RASs were rarely observed and presence did not seem to impact SVR, regardless of the use of RBV.

Full article:
https://onlinelibrary.wiley.com/doi/full/10.1111/apt.14592

Monday, January 8, 2018

Epclusa - Study Backs Hepatitis C Treatment in Injection Drug Users

Study Backs Hepatitis C Treatment in Injection Drug Users
By Amy Orciari Herman
Edited by Susan Sadoughi, MD, and André Sofair, MD, MPH

Use of sofosbuvir-velpatasvir to treat hepatitis C virus (HCV) infection in injection drug users usually leads to a sustained virologic response at 12 weeks, according to an industry-supported study in the Lancet Gastroenterology & Hepatology.


Monday, December 18, 2017

China: MSF challenges Gilead’s patent application for hepatitis C treatment

In case you missed it

China: MSF challenges Gilead’s patent application for hepatitis C treatment

Médecins Sans Frontières (MSF) has filed a legal patent challenge in China against US pharmaceutical corporation Gilead’s patent application for the combination of two crucial oral hepatitis C medicines, sofosbuvir and velpatasvir. This combination is the first direct-acting antiviral (DAA) treatment to be registered for use against all genotypes of the disease. Rejection of patents for this combination would pave the way towards the availability of affordable generic versions of this treatment that millions of people need in China and around the world....

Monday, October 23, 2017

The Liver Meeting® 2017 - Is Ribavirin Really Needed for Patients With HCV Genotype 3 on Sofosbuvir/Velpatasvir 

Is Ribavirin Really Needed for Patients With HCV Genotype 3 on Sofosbuvir/Velpatasvir
By Andrew D. Bowser
The findings add new perspective to the ongoing discussion among researchers and clinicians as to whether adding ribavirin might prevent a relapse in patients with HCV genotype 3, particularly if they were previously treated.

Results of the current study represent “real world” experience with patients with HCV genotype 3 treated at 9 sites in Germany, according to Stefan Christensen, MD, Department of Infectious Diseases, Center for Interdisciplinary Medicine, Muenster, Germany.

“We could confirm the high SVR12 rates [sustained virologic response at 12 weeks] from the clinical phase 3 studies with sofosbuvir/velpatasvir, [but] in our cohort, it seems like the addition of ribavirin in cirrhotic patients did not have further benefit for those patients,” he said.
Read the article @ FirstWord Pharma

Of Interest - FirstWord Pharma

The Liver Meeting® 2017 - Mavyret (Glecaprevir/Pibrentasvir) for Treatment-Naive Patients With HCV Genotype 3

NAM Publications
An integrated analysis of clinical trial data showed that glecaprevir/pibrentasvir taken for 8 weeks cured 98% of people without cirrhosis with hard-to-treat genotype 3, while a 12-week course cured 100% of people with genotype 3 with cirrhosis. A related analysis showed that the combination taken for 12 or 16 weeks cured 96% of people with compensated cirrhosis across all genotypes.

Steven Flamm of Northwestern Feinberg School of Medicine in Chicago and colleagues performed an integrated analysis of efficacy and safety data from phase 2 and 3 clinical trials of glecaprevir/pibrentasvir for previously untreated people with HCV genotype 3, either without cirrhosis or with compensated cirrhosis.
Read the article @ aidsmap

aidsmap coverage
Conference news: The Liver Meeting

NATAP
WASHINGTON, DC -- October 23, 2017 -- Glecaprevir/pibrentasvir was well-tolerated and resulted in high virologic response rates in treatment-naive patients with hepatitis C virus (HCV) genotype 3 infection, according to a study presented here at The Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
Read the article @ FirstWord Pharma

Of Interest - HCV Genotype 3
Of Interest - FirstWord Pharma
By Andrew D. Bowser
The findings add new perspective to the ongoing discussion among researchers and clinicians as to whether adding ribavirin might prevent a relapse in patients with HCV genotype 3, particularly if they were previously treated.

Results of the current study represent “real world” experience with patients with HCV genotype 3 treated at 9 sites in Germany, according to Stefan Christensen, MD, Department of Infectious Diseases, Center for Interdisciplinary Medicine, Muenster, Germany.

“We could confirm the high SVR12 rates [sustained virologic response at 12 weeks] from the clinical phase 3 studies with sofosbuvir/velpatasvir, [but] in our cohort, it seems like the addition of ribavirin in cirrhotic patients did not have further benefit for those patients,” he said.
Read the article @ FirstWord Pharma

FirstWord Pharma