Welcome to HCV Advocate’s hepatitis blog. The intent of this blog is to keep our website audience up-to-date on information about hepatitis and to answer some of our web site and training audience questions. People are encouraged to submit questions and post comments.

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Alan Franciscus
Editor-in-Chief
HCV Advocate
HBV Advocate

Tuesday, April 15, 2014

Chronic Hepatitis C Genotype 4: RESTORE Study Results

MedicalResearch.com Interview with:
Christophe Moreno, MD, PhD
Directeur clinique, clinique d’Hépatologie
Service de Gastroentérologie
Hépatopancréatologie et Oncologie Digestive

MedicalResearch.com: What are the main findings of the study?

Dr. Moreno: The RESTORE study is an open label, phase 3 study, evaluating Simeprevir in combination with PegIFN and ribavirin in genotype 4 Chronic Hepatitis C patients, either naïve or treatment experienced. Results of this study demonstrated high efficacy of this combination, with an overall SVR rate of 65.4%. Efficacy is particularly high in treatment naïve and prior relapsers patients, with SVR rate of 82.9% and 86.4%, respectively.

Moreover, treatment naïve patients and prior relapsers were eligible to a shorter treatment duration of 24 weeks if they met response-guided therapy (RGT) criteria (defined by an HCV RNA below 25 at week 4 and undetectable at week 12). 89.5% met RGT criteria. Of those, 94.1% achieved a SVR.

Read more....

BI rethinks hepatitis business, posts 2013 results

Family-owned Boehringer Ingelheim is bracing for a rough 2014. The drugmaker indicated in its 2013 annual report that “we can expect to face challenges,” and that it is not expecting BI, let alone the industry, to experience a significant upswing within the next 12 months.

This was not the German company's only downbeat news: BI has also indicated it has stepped out of the interferon-free Hepatitis C race. The company said Phase III results of interferon-free use of faldaprevir and deleobuvir “did not live up to expectations,” and the company has terminated development of the combination.

Although BI says it expects to get approvals for an interferon-faldaprevir treatment this year, the company “will now have to examine our activities in the field of hepatitis C therapy in depth, also in view of convincing clinical data from competitors in the field."

Read more...

New England Journal of Medicine - AbbVie, by Alan Franciscus (epub ahead of print)

 
  —Alan Franciscus, Editor-in-Chief


The information below is a review of three recently published studies that appeared in the New England Journal of Medicine (NEJM) in April 2014.  This type of information from a prestigious journal like the New England Journal of Medicine that was peer-reviewed lends more credibility to the information of the study results.   

AbbVie
There were 3 journal articles about AbbVie’s all oral medications released in the NEJM in April 2014—Phase 3 studies for the treatment of HCV genotype 1a & 1b (treatment-naïve, treatment-experienced, and treatment-experienced patients with cirrhosis).

The medications used in the studies included:
  • HCV protease inhibitor, 150mg ABT-450/r (ritonavir 100mg),
  • HCV NS5A inhibitor, 25 mg ombitasvir (formerly ABT-267),
  • HCV polymerase inhibitor 250mg dasabuvir (formerly ABT-333) and,
  • Ribavirin dosed by body weight. 
Note: ABT-450/r and ombitasvir are co-formulated into one pill, taken once-a-day.  Dasabuvir and ribavirin are taken twice daily.

#1 – Treatment Naïve (SAPPHIRE-I):

Patient Population:
There were two groups in this study—the information has been combined for this article.  There were a total of 631 patients who received at least one dose of the study drugs.  The majority of patients were male (344 pts), White (572 pts), and ~50 yo.  There were 427 patients with HCV genotype 1a and 204 patients with HCV genotype 1b.  There were no patients with cirrhosis.  The treatment duration was 12 weeks.  There were two different groups (group A and B) who were treated at different time points—group A received the AbbVie drugs at day 1.  Group B received placebo drugs at day 1 through week 12 and then received the AbbVie drugs beginning at the end of the week 12 placebo period.  This meant that they could have a comparator arm, but it also gave the placebo group an opportunity to receive the study drugs.  

Results: 
Overall cure rates were 96.2%—genotype 1a cure rates at 95.3% and 98.0% in the genotype 1b patients.  The cure rates were comparable between all groups (HCV genotype subtype, viral load, race, IL28B)

Side Effects: 
The most common side effects were fatigue and headache.  The rate of serious side effects was low (2.1%) and the rate of treatment discontinuation was also low (0.6%).

Comments: 
The data speaks for itself—high cure rates across all populations with hepatitis C infection, low rates of side effects and very few treatment discontinuations.  In addition, the study design allowed the placebo group to receive the entire course of therapy with the AbbVie drugs after the end of the placebo period—this is a real win for everyone and I hope more pharmaceutical companies will provide this in their clinical studies.

#2 – Retreatment (SAPPHIRE-II):

Patient Population: 
There were 297 patients who received the study drug (97 patients received placebo).  I am only including the information from the group that received the study drug.  Most of the patients were male (167 pts), White (269 pts), age ~52 yo, genotype 1a (173 pts), and genotype 1b (123 pts).  The treatment duration was 12 weeks. 

Results: 
  • All patients – cure: 96.3% (cure rates the same in genotype 1a and 1b)
  • Relapsed patients – cure:  95.3%
  • Prior partial response – cure:  100%
  • Prior null response – cure:  95.2%
Side Effects:  The most common side effects reported in group that received the study drug vs. the placebo group were headache (36.4% vs. 35.1%) and fatigue (33.3% vs. 22.7%).  Itching occurred more frequently in the group that received the study drugs (13.8% vs. 5.2%). There were 1.3% treatment discontinuations.  

Comments:  These results are impressive especially in the group of prior null-responder patients who are the most difficult to cure—95.2% in the AbbVie drugs compared to historical cures of up to 53% with interferon and ribavirin-based therapies that included telaprevir, boceprevir or simeprevir. 

#3—Treatment-Naïve & Treatment-Experienced Patients with Compensated Cirrhosis (TURQUOISE-II):

Patient Population: 
  • Group A:  12 weeks of treatment—208 patients, the majority of patients were male (146 pts), White (199 pts), age (~57 yo), genotype 1a (140 pts), and genotype 1b (68 pts)
  • Group B:  24 weeks of treatment—172 patients, the majority of patients were male (121 pts), White (161 pts), age (~56 yo), genotype 1a (121 pts), and genotype 1b (51 pts). 
Results:
The cure rates by treatment group, genotype subtype (1a or 1b), and type of prior response are listed below:

(A) 12 Week Group
(B) 24 Week Group
HCV Genotype 1a
  • Treatment naïve
92.2% (59 of 64 pts)
92.9% (52 of 56 pts)
  • Prior null response
80% (40 of 50 pts)
92.9% (39 of 42 pts)
  • Prior partial responders
100% (11 of 11 pts)
100% (10 of 10 pts)
  • Prior relapsers
93.3% (14 of 15 pts)
100% (13 of 13 pts)

HCV Genotype 1b
  • Treatment naïve
100% (22 of 22 pts)
100% (18 of 18 pts)
  • Prior null response
100% (25 of 25 pts)
100% (20 of 20 pts)
  • Prior partial responders
85.7% (6 of 7 pts)
100% (3 of 3 pts)
  • Prior relapsers
100% (14 of 14 pts)
100% (10 of 10 pts)

Side Effects:
There were more side effects in the 24-week treatment group—no big surprise there.  The most common side effects (in more than 18% of patients in both groups) were fatigue, headache, nausea and itching.  Two percent of the trial participants discontinued treatment due to side effects. 

Comments: 
As in the other AbbVie studies the cure rates are remarkable and the side effects were low—this is especially important in this group of patients who typically have higher rate and severity of side effects. The study found that most of the patients in the study had similar cure rates regardless of treatment duration.  The only group that may need 24 weeks of treatment with the AbbVie combination is the HCV genotype 1a prior null-responders—80% in the 12 week group vs. 92.9% in the 24 week group. 

It is also important to know that people who are typically excluded from studies (compensated cirrhotic patients with thrombocytopenia (low platelets), hypoalbuminemia (low albumin) or major depression) were enrolled in the study and achieved similar cure rates to those in the other study arms.  This is a patient population that is at the highest risk for severe disease progression, and treatment for this group should be a priority for the development of safe and effective drugs. This study proves that even these patients who are the most difficult to treat can be safely treated and cured.

Mechanism Helps Explain Persistence of Hepatitis C Virus

Researchers at the University of California, San Diego School of Medicine have identified a mechanism that explains why people with the hepatitis C virus get liver disease and why the virus is able to persist in the body for so long.

The hard-to-kill pathogen, which infects an estimated 200 million people worldwide, attacks the liver cells' energy centers – the mitochondria – dismantling the cell's innate ability to fight infection. It does this by altering cells mitochondrial dynamics.

The study, published in today's issue of the Proceedings of the National Academy of Sciences, suggests that mitochondrial operations could be a therapeutic target against hepatitis C, the leading cause of liver transplants and a major cause of liver cancer in the U.S.

Read more...

EASL 2014: Treatment as Prevention for Drug Users Could Slash HCV Prevalence

A combination of increased testing, improved linkage to care, and earlier treatment with interferon-free regimens has the potential to substantially reduce the incidence and prevalence of hepatitis C among people who inject drugs in France over the next 10 years, as well as reducing the burden of disease arising from cirrhosis over 40 years, according to a study presented at the 49th EASL International Liver Congress (EASL 2014) last week in London.

Using treatment to reduce the rate of new infections is already an established aim of antiretroviral treatment for HIV, although the full potential of the strategy is still being tested in large studies.

Several research groups have likewise developed models of the impact of hepatitis C treatment on new infections, focusing in particular on HCV incidence among people who inject drugs, where rates of transmission continue to be high in many settings.

Read more....

Sunday, April 13, 2014

Meet the HCV Expert, April 17, 2014: Falls Church VA


To register, please call 1-877-925-9550 or email info@ChronicLiverDisease.org

Destigmatizing Hepatitis C

To destigmatize Hepatitis C, education and information are key.

When Debbie Panarase learned she had Hepatitis C nearly 20 years ago, she kept things to herself.

“I was very closed-mouth about it at first because when I did start learning about it, it was IV drug users,it was sexually transmitted, it was all the things that I had never done before,” she says. “I did not want that stigma to follow me.”

As she learned more, she opened up and even started support group for others in the Chicago area.

Read more and watch the video here...