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.

For more information on how to use this blog
click here, the HCV drug pipeline click here, and for more information on HCV clinical trials click here

Be sure to check out our other blogs: The HBV Advocate Blog and Hepatitis & Tattoos.

Alan Franciscus
Editor-in-Chief
HCV Advocate
HBV Advocate

Drugs in Development / Clinical Trials—Updated March 17, 2015

Friday, May 29, 2015

Senator Kirk Joins American Legion to Raise Hepatitis C Awareness for Veterans

Kirk’s Veterans Bill Passed by Appropriations Committee Funds $900 Million Worth of Groundbreaking New Hepatitis C Treatments; Veterans Suffer From Hepatitis C at a Rate Three Times That of the Civilian Population

Summit, Ill. --(ENEWSPF)--May 29, 2015.  In an effort to raise hepatitis C virus (HCV) awareness for veterans, U.S. Senator Mark Kirk (R-Ill.) joined Marty Conatser, Adjutant of the American Legion Department of Illinois, Paul Gardner, Senior Vice Commander of the American Legion Department of Illinois, and Argo Summit Post Commander Reggie Rice at a free Hepatitis C testing event in Summit, IL. Service Officers from the American Legion and representatives from the Department of Veterans Affairs were also present to counsel veterans on VA benefit claims and recommend next steps for HCV medical care to any veterans that tested positive for the virus.

“In the Department of Veterans Affairs we have cured more people of Hepatitis C in the last 16 months than in the last 16 years,” Senator Kirk said. “We will continue work to make sure that those who wore the uniform can have a better life.”

Read more...

Lee County Health Department offers Hep C rapid test

Also looks into creating a needle exchange in response to heroin increase in county 

 DIXON – It's not just law enforcement agencies that are taking a proactive approach to Lee County's increased heroin usage — the health department is making strides, too.

This week, the Lee County Health Department started offering rapid screening for Hepatitis C. It's an action that Administrator Cathy Ferguson hopes will stave off any future heroin-related public health crises, like the one that southeastern Indiana has seen.

According to the latest figures, there are now 162 people in Indiana who have been diagnosed with HIV as part of an outbreak that, officials say, stemmed from the sharing of heroin needles.

Meeting Report Now Available: Hepatitis C among African Americans

African Americans are among the populations prioritized by the Action Plan for the Prevention, Care, and Treatment of Viral Hepatitis (Action Plan) which outlines steps to educate communities about the benefits of viral hepatitis prevention, care, and treatment as well as actions to enhance healthcare provider knowledge about populations disproportionately impacted. A two-day forum convened by HHS in March 2015 focused on strengthening the response to hepatitis C in African American communities and included participation from over 30 organizations from across the country. The Action Plan is a national plan that requires the participation and engagement of many partners in order to achieve its goals and the newly released forum report includes themes and strategic considerations that all stakeholders can use to address the important health disparity of hepatitis C among African Americans in the United States.

Read the full report from the HHS Forum on Hepatitis C in African American Communities (PDF 8.4MB)

- See more at: https://blog.aids.gov/2015/05/meeting-report-now-available-hepatitis-c-among-african-americans.html#sthash.8N3zjGUp.dpuf

Phase I/II Opdivo (nivolumab) Trial Shows Bristol-Myers Squibb’s PD-1 Immune Checkpoint Inhibitor is First to Demonstrate Anti-Tumor Activity In Patients With Hepatocellular Carcinoma

  • Interim results show favorable safety profile of Opdivo, and durable responses in previously-treated patients
  • Overall survival rate of 62% at 12 months observed at this interim analysis
  • Hepatocellular carcinoma is the second most frequent cause of cancer-related death worldwide and remains an area of significant unmet medical need
  • Patients with hepatocellular carcinoma who have relapsed or have disease progression, following standard of care, have a median survival with best supportive care of ~7 to 8 months

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced results from an interim analysis of CA209-040, a Phase I/II dose-ranging trial evaluating the safety and anti-tumor activity of Opdivo (nivolumab) in previously-treated patients with hepatocellular carcinoma (HCC) or advanced liver cancer. Initial findings demonstrated that the estimated survival rate in evaluable patients (n=47) was 62% at 12 months. Results also show the safety profile of Opdivo is generally consistent with that previously-reported for Opdivo in other tumor types. These data will be featured today, May 29, during the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) press briefing at 1:00 – 2:00 p.m. CDT and presented on Saturday, May 30 from 8:27 a.m. – 8:39 a.m. CDT (Late Breaking Abstract #101).

“Hepatocellular carcinoma is an aggressive and fatal cancer, comprising 90 percent of all liver cancer in adults worldwide with limited therapeutic options for patients with advanced stage disease; no treatment advances have been made for patients who fail to respond or progress on the current standard of care,” said Anthony B. El-Khoueiry, MD, lead study author and associate professor of clinical medicine and phase I program director at the University of Southern California Norris Comprehensive Cancer Center. “These preliminary data are encouraging and support the ongoing evaluation of nivolumab in this patient population, as they show promising preliminary survival data, and durable partial or complete response in one out of five nivolumab-treated patients, with many others experiencing stable disease.”

More than 700,000 people around the world are diagnosed with HCC each year with a majority of all HCC cases caused by infection with the hepatitis B virus (HBV) or hepatitis C virus (HCV), making HBV/HCV the most common risk factor for liver cancer worldwide. Patients with advanced HCC receiving the current standard of care have a median overall survival of less than 1 year. For patients who have relapsed or have disease progression, median survival with best supportive care is approximately 7 to 8 months.

“Bristol-Myers Squibb’s experience in hepatitis and Immuno-Oncology make us poised as leaders to advance Opdivo into additional studies of hepatocellular carcinoma,” said Michael Giordano, senior vice president, Head of Development, Oncology, Bristol-Myers Squibb. “Opdivo has demonstrated improvements in survival in a number of different tumor types. We are excited that this trial has shown the potential that this may extend to advanced liver cancer and hope to confirm these findings in future trials.”

About the CA209-040
CA209-040 is a Phase I/II dose-ranging trial that evaluated the safety and anti-tumor activity of Opdivo in patients with HCC, the majority of whom had received prior treatment. The trial included 47 HCC patients who were enrolled into one of three treatment arms depending on whether or not they were infected with HCV or HBV. Patients enrolled in the trial received Opdivo doses ranging from 0.1 – 10 mg/kg intravenously every 2 weeks for up to 2 years. The primary objective was safety, tolerability, dose limiting toxicities, and maximum tolerated dose. Anti-tumor activity was a secondary objective (using RECIST 1.1 criteria), and overall survival was an exploratory objective.

As of this interim analysis, 62% of patients in the study were still alive after 12 months. Eight (19%) patients (of 42 evaluable patients) achieved a complete or partial response, meaning that the size of their tumors measured at baseline decreased by 30–100% with Opdivo treatment. In patients with response, duration of response ranged from more than 1.4 – 12.5 months. Seventeen patients remained on study treatment and 30 discontinued treatment due to progressive disease (n=26), complete response (n=2), or adverse events (n=2).

CA209-040 is the first trial to characterize the safety profile of Opdivo monotherapy in patients with HCC, including those with HCV and HBV infections. In the trial, safety and tolerability were well-characterized, with the frequency and intensity of treatment-related adverse events (AEs) being consistent across Opdivo dose levels. The majority of side effects were mild to moderate in nature with abnormal liver enzymes (19% AST and 15% ALT), rash (17%) and elevation of amylase (15%) and lipase (17%) being the most common; the abnormal liver enzymes and elevated amylase and lipase were not accompanied by any significant clinical symptoms. Grade 3–4 treatment-related AEs were infrequent (19%). There were no treatment-related deaths reported.

About Opdivo
Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials – as monotherapy or in combination with other therapies – in which more than 8,000 patients have been enrolled worldwide.

Opdivo became the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world on July 4, 2014 when Ono Pharmaceutical Co. announced that it received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma. In the U.S., the U.S. Food and Drug Administration (FDA) granted its first approval for Opdivo for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. On March 4, 2015, Opdivo received its second FDA approval for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.

Read complete press release here
 

Thursday, May 28, 2015

Merck Submits U.S. New Drug Application for Grazoprevir/Elbasvir, an Investigational Once-Daily, Single Tablet Combination Therapy, for Treatment of Chronic Hepatitis C Genotypes 1, 4, and 6 Infection

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the company has submitted a New Drug Application to the U.S. Food and Drug Administration (FDA) for grazoprevir/elbasvir (100mg/50mg), an investigational once-daily, single tablet combination therapy for the treatment of adult patients with chronic hepatitis C genotypes (GT) 1, 4 or 6 infection. Within 60 days of submission, the FDA will determine whether it will accept for review Merck's application as filed. The company plans to submit additional license applications in the European Union and other markets by the end of 2015.

“Merck's submission is based on evidence from our wide-ranging clinical program assessing the efficacy and tolerability profile of grazoprevir/elbasvir in populations with chronic hepatitis C,” said Dr. Roy Baynes, senior vice president of clinical development, Merck Research Laboratories. “This submission to the U.S. FDA is an important milestone as we seek to provide patients with a new treatment option for this serious infection.”

The FDA has previously granted Breakthrough Therapy designation status for grazoprevir/elbasvir for the treatment of patients infected with chronic HCV GT1 with end stage renal disease on hemodialysis, and for patients infected with chronic HCV GT4. Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

The New Drug Application for grazoprevir/elbasvir (100mg/50mg) is based in part upon data from the pivotal C-EDGE clinical trials program, as well as the C-SURFER and C-SALVAGE trials, evaluating grazoprevir/elbasvir (100mg/50mg), with or without ribavirin, in patients with chronic hepatitis C infection. Data from these trials were presented at The International Liver CongressTM 2015 in April 2015.
 
About Grazoprevir/Elbasvir
Grazoprevir/elbasvir is an investigational, once-daily single tablet regimen consisting of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A replication complex inhibitor). As part of Merck’s broad clinical trials program, grazoprevir/elbasvir is being studied in multiple HCV genotypes and in patients with difficult-to-treat conditions such as HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, liver cirrhosis and those on opiate substitution therapy.
 
About Merck
Today’s Merck is a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.
 
Read the complete press release here

Harvoni added benefit for patients with HCV/HIV coinfection

In a manufacturer dossier assessment conducted by the Institute for Quality and Efficiency in Health Care in Germany, Harvoni was deemed to have an added benefit for patients with hepatitis C genotype 1a virus infection and HIV without cirrhosis, according to a press release.

The dossier assessment is a procedural part of the Reform of the Market for Medicinal Products Act, overseen by the Federal Joint Committee (G-BA). The G-BA conducts a commenting procedure once the dossier assessment is complete and then determines the extent of the added benefit determined by the Institute for Quality and Efficacy in Health Care (IQWiG).

The assessment was based on additional data from five clinical studies submitted by Gilead Sciences. The information led the IQWiG to conclude that SVR achieved by patients without HIV coinfection was “transferable” to patients with HIV coinfection without cirrhosis. However, the extent of the added benefit in this population of patients is “non-quantifiable” due to the fact it is unclear in how many patients with undetectable viral load prevention of late complications and liver cancer can be achieved, according to the release.

Wednesday, May 27, 2015

Cooperation among viral variants helps hepatitis C survive immune system attacks

Warring armies use a variety of tactics as they struggle to gain the upper hand. Among their tricks is to attack with a decoy force that occupies the defenders while an unseen force launches a separate attack that the defenders fail to notice.

A study published earlier this month in the journal Proceedings of the National Academy of Sciences suggests that the Hepatitis C virus (HCV) may employ similar tactics to distract the body's natural defenses. After infecting patients, Hepatitis C evolves many variants, among them an "altruistic" group of viral particles that appears to sacrifice itself to protect other mutants from the body's immune system.

The findings, reported by researchers from the Georgia Institute of Technology and the Centers for Disease Control and Prevention (CDC), could help guide development of future vaccines and treatments for the virus, which affects an estimated 170 million people in the world. Developing slowly over many years and often without symptoms, Hepatitis C can cause severe liver damage and cancer. There are currently no vaccines for the disease.

Read more....