Should We Be Rationing Hepatitis Drugs? Obama Pressured to End Restrictions

Amid mounting evidence that federal and state authorities are rationing costly new wonder drugs for treating people with the potentially lethal hepatitis C virus, public health experts have begun pressing the White House to intervene to expand the use of Sovaldi and other new medications.

An estimated 3.2 million adults are chronically infected with hepatitis C while an estimated 20,000 people die from the serious liver ailment every year, including many military veterans.

The New York Times reported on Tuesday that a group of experts from the Public Health Service and President Obama’s Advisory Council on H.I.V./AIDS wrote a letter to the White House complaining that restrictions on the use of these drugs by many states are inconsistent with prudent and sound medical practices. Read more....

EASL 2015: Part 2 —Alan Franciscus, Editor-in-Chief

In part 2 of our European Association for the Study of the Liver (EASL) coverage I will wrap up with a brief overview of some of the remaining data. 

AbbVie:  Ombitasvir/Paritaprevir/Ritonavir for Treatment of HCV Genotype 1b In Japanese Patients with or without Cirrhosis: Results from Gift-I –K Chayama et al

In this current study, Japanese patients were treated with AbbVie’s 2D (paritaprevir/ritonavir plus ombitasvir) given once-a-day for 12 weeks.  This is different from the 3D regime given in the United States and elsewhere because Japanese patients metabolize AbbVie’s drugs differently.  With the 2D combinations Japanese patients reach high enough levels even without ribavirin or dasabuvir.    

In the study there were 215 HCV genotype 1b patients who received the study drugs, 42% were cirrhotic, and 35% were treatment experienced.  The overall cure rate was 95%.  The cure rates among those who had never been treated, as well as those who were treated previously (cirrhotic and non-cirrhotic) were all similar.  The most common side effects were headache, edema and sore throat. 

Comments:  Japan has a long history of hepatitis C.  AbbVie’s 2D combination will be a welcome addition to the drugs in Japan to treat Japanese patients.  For more information about HCV in Japan check out our HCV in Japan—HCV Around the World series.

 

NHANES:  Advanced Fibrosis is Common in Individuals whose Hepatitis C Has Not Been Diagnosed: Results from the National Health and Nutrition Examination Survey 2001-2012—P Udompap et al

This study has been reported at previous conferences, but it is worth discussing again.  The National Health and Nutrition Examination Survey (NHANES) used data from a group of 62,000 American adults of whom 45,000 were tested for hepatitis C antibodies—591 tested antibody positive and of those 420 were HCV RNA or viral load positive. 

Of the 420 who had chronic hepatitis C, 1 in 10 had cirrhosis and 1 in 5 had advanced fibrosis.  Approximately 50% did not know that they had hepatitis C. 

Comments:  This validates the recommendation for “Baby Boomer” testing.  This should WAKE UP the complacency among physicians and associations and start testing baby boomers NOW.  We want to test, monitor, treat, cure and save lives.

 

Gilead:  Ledipasvir/sofosbuvir treatment results in high SVR rates in patients with chronic genotype 4 and 5 HCV infection— A Abergel et al

A total of 44 HCV genotype 4 patients and 41 HCV genotype 5 patients were treated with the combination of sofosbuvir and ledipasvir for 12 weeks.  In both of the groups the patients were evenly divided between treatment experienced (TE) and those who had never been treated (TN) and those with and without cirrhosis (C & w/o C).  The cure rates in the HCV genotype 4 patients was TN =96% (21 of 22 pts); TE = 91% (20 of 22 pts); C= 100% (10 of 10 pts); w/o C = 91% (31 of 34 pts).  The most common side effects were fatigue and headache.

 

Comments:  These are very good cure rates with few side effects.  While the population of genotype 4 and 5 in the United States is very low—genotype 4 is very high in Egypt and other parts of the world (see HCV in Egypt in our HCV Around the World series).  Genotype 5 is primarily seen in South Africa and parts of Europe.  I will be writing an article on Genotype 5 for the June Mid-Monthly edition so stay-tuned.

 

Merck: The Phase 3 C-Edge Treatment-Naive (TN) Study of a 12-Week Oral Regimen of Grazoprevir (GZR, MK-5172)/Elbasvir (EBR, MK-8742) in Patients with Chronic HCV Genotype (Gt) 1, 4, or 6 Infection—S Zeuzem et al

This was a phase 3 study of a one pill, once-a-day grazoprevir and elbasvir pill taken for 12 weeks.  The study included treatment naïve (TN). The trial included a total of 421 infected HCV genotype 1, 4 or 6.  Most of the trial participants were male sex, and White.  Ninety-one percent were genotype 1.   Approximately 22% had cirrhosis. 

The overall cure rate was 95%: 92% for genotype 1a and 99% for genotype 1b; 100% (36 of 36 pts) of the genotype 4 patients were cured; 80% (5 of 6 pts) of genotype 6 patients were cured.  The most common side effects were headache, fatigue, nausea and joint pain.

 
Comments:  These are high cure rates with a low side effect profile and it will make a good addition to the treatment landscape of HCV in 2016.  In people with the genotype 1a NS5A resistance-associated variants (RAVs) it shows greater than a 5-fold loss in sensitivity to elbasvir (a protease inhibitor).  What this means in clinical practice in unknown at this time.

http://hcvadvocate.org/news/newsLetter/2015/advocate0615.html#1

AbbVie Presents New Data for its Investigational Hepatitis C Treatment in Japanese Patients With and Without Cirrhosis

- New data from GIFT-I study presented at the Annual Meeting of the Japan Society of Hepatology

- Primary endpoint of 95 percent and secondary endpoint of 91 percent SVR12 achieved in genotype 1b hepatitis C virus infected Japanese patients without and with compensated cirrhosis, respectively(1)

- 98 percent SVR12 achieved in additional analysis of patients without cirrhosis receiving double-blind placebo for 12 weeks, followed by open-label therapy with AbbVie's investigational treatment(1)

- AbbVie's ribavirin-free treatment for genotype 1 hepatitis C Japanese patients consists of a 12-week, two direct-acting antiviral, fixed-dosed combination of paritaprevir/ritonavir with ombitasvir, dosed once daily

NORTH CHICAGO, Ill., May 26, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV) presented new results from the Phase 3 GIFT-I study of its investigational, all-oral, interferon (IFN)- and ribavirin (RBV)-free, two direct-acting antiviral treatment with ombitasvir/paritaprevir/ritonavir at the Annual Meeting of the Japan Society of Hepatology in Kumamoto, Japan.¹ GIFT-I evaluated genotype 1b (GT1b) chronic hepatitis C virus (HCV) infected Japanese patients, with and without cirrhosis, who were either treatment-naïve or IFN (with or without RBV) treatment-experienced.¹ The primary endpoint was achieved, demonstrating 95 percent (n=106/112) SVR₁₂ in a sub-group of treatment-naïve, non-cirrhotic, adult GT1b HCV infected Japanese patients who were eligible for therapy with IFN and had a high viral load.¹ In study results related to the secondary endpoint, GT1b HCV patients with compensated cirrhosis achieved 91 percent (n=38/42) SVR₁₂.¹

In an additional intent-to-treat (ITT) analysis, SVR₁₂ was achieved in 98 percent (n=104/106) of the GT1b HCV infected patients without cirrhosis (Arm B) who were randomized to initially receive double-blind placebo for 12 weeks, followed by open-label treatment with ombitasvir/paritaprevir/ritonavir.¹ The ITT population included every patient that was randomized to placebo and received at least one dose of active, open-label study drug.

"It is critical to address the burden of hepatitis C in Japan, with GT1b being the most prevalent sub-type of the disease in the country," said Kazuaki Chayama, M.D., Ph.D, professor and head of the Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University. "GIFT-I shows the potential of this treatment to achieve high SVR rates for Japanese patients with GT1b hepatitis C, including those with compensated cirrhosis."

Across all study arms, three patients (n=3/363) discontinued treatment due to adverse events.¹ The most commonly reported adverse events (>5 percent in any arm) were nasopharyngitis, headache, peripheral edema, nausea, pyrexia and decreased platelet count.¹

"We are pleased to present full results from GIFT-I, which provide further insight into our hepatitis C treatment currently under priority review by the Japanese health authorities," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "We know physicians weigh the risks and benefits of HCV treatments for their patients as they look for an option that offers a potential cure. These data will help guide clinicians in their decision making and support AbbVie's goal of bringing an interferon- and ribavirin-free treatment to people living with genotype 1 hepatitis C in Japan."

In Japan, approximately 1.5 to 2 million people are living with HCV.² Genotype 1 is the most common HCV genotype in Japan with 60 to 70 percent of patients infected and, of those, about 95 percent are infected with the GT1b sub-type.³ AbbVie studied its two direct-acting antiviral treatment regimen without RBV in Japan due to patient and viral characteristics specific to the Japanese population, including high prevalence of GT1b.

AbbVie's investigational, two direct-acting antiviral treatment consists of ombitasvir/paritaprevir/ritonavir and is currently under priority review by the Japanese Ministry of Health, Labour and Welfare.

About GIFT-I Study
GIFT-I comprises 363 patients in two sub-studies. In sub-study 1, 321 genotype 1b (GT1b) patients without cirrhosis, both treatment-naïve and interferon (IFN) [with or without ribavirin (RBV)] treatment-experienced, were randomized to receive either ombitasvir/paritaprevir/ritonavir (Arm A) [OBV/PTV/r] or placebo (Arm B) [2:1 randomization ratio, stratified by treatment history, past response, viral load and IFN eligibility]. Patients initially randomized to placebo (Arm B) then received OBV/PTV/r for an additional 12 weeks of open-label treatment. Sustained virologic response was assessed 12 weeks post-treatment (SVR₁₂) as a primary efficacy endpoint in a sub-group of previously untreated, non-cirrhotic GT1b patients who were eligible for therapy with IFN and had a high viral load, defined as an HCV RNA level ≥ 100,000 IU/mL and received at least one dose of the double-blind, active study drug.¹

In sub-study 2, 42 GT1b treatment-naïve and IFN (with our without RBV) treatment-experienced patients with compensated cirrhosis received open-label treatment for 12 weeks (Arm C) with SVR₁₂ and assessed as a secondary efficacy endpoint.¹

One patient from each arm (n=3/363) experienced on-treatment virologic failure [Arm A, 0.5% (n=1/215); Arm B, 0.9% (n=1/106); Arm C, 2.4% (n=1/42)].¹ Across all arms, eight patients (n=8/354) experienced post-treatment relapse [Arm A, 2.4% (n=5/209); Arm B, 1.0% (n=1/105); Arm C, 5.0% (n=2/40)].¹  

About AbbVie's Investigational Two Direct-Acting Antiviral HCV Treatment
For the treatment of genotype 1 chronic hepatitis C virus (HCV) infection in Japan, AbbVie's investigational, two direct-acting antiviral treatment consists of the fixed-dosed combination of paritaprevir/ritonavir (150/100 mg) with ombitasvir (25 mg), dosed once daily.

AbbVie's chronic HCV treatment combines two direct-acting antivirals, each with a distinct mechanism of action that targets and inhibits specific HCV proteins of the viral replication process.

About AbbVie's HCV Clinical Development Program in Japan
AbbVie's HCV clinical development program in Japan focuses on our investigational, two direct-acting antiviral treatment and is designed with the goal of achieving high SVR rates in chronic HCV infected patients, including additional genotypes and patients with compensated cirrhosis.

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

Ombitasvir/paritaprevir/ritonavir is an investigational product and its safety and efficacy have not been established in Japan.

Additional information about AbbVie's clinical development program in Japan can be found on www.clinicaltrials.gov.

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

Read the complete press release here