Sunday, April 7, 2013

Sofosbuvir/ Ledipasvir -An ‘apocalypse moment’ for HCV?

GI & Hepatology News is the official newspaper of the AGA Institute and provides the gastroenterologist with timely and relevant news and commentary about clinical developments and about the impact of health-care policy. The newspaper is led by an internationally renowned board of editors.

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(VOL. 7 NO. 5 APRIL 2013):
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Issue Highlights

Interferon-free HCV regimen cured all genotype 1 patients
Included: sofosbuvir, ledipasvir, ribavirin..

Medical News ATLANTA –

Adding ledipasvir to sofosbuvir and ribavirin produced sustained virological responses 12 weeks after therapy in 100% of treatment-naive and prior nonresponder patients with chronic hepatitis C genotype 1 in the ELECTRON trial. “Certainly adding a second direct-acting antiviral agent, ledipasvir, increases the efficacy of sofosbuvir plus ribavirin,” Dr. Edward Gane said at the Conference on Retroviruses and Opportunistic Infections. Three-quarters of the roughly 170 million people infected with hepatitis C virus (HCV) worldwide have genotype 1, the most difficult strain to treat. Current treatment includes triple therapy with a protease inhibitor plus peginterferon and ribavirin for 24-48 weeks, but PIbased therapy is limited by complex dosing regimens, the potential for resistance, and lower responses in prior nonresponders, explained Dr. Gane of Auckland Clinical Studies in New Zealand. The investigators hypothesized that combining two direct-acting antivirals with a different mechanism would enhance response.......

Ledipasvir and sofosbuvir have been combined into a single fixeddose tablet and it is being evaluated in phase III studies in patients with cirrhosis and to determine whether there is a need for ribavirin, he said. Additional studies are also underway to explore shorter durations of therapy. The ELECTRON trial was sponsored by Gilead Sciences. Dr. Gane reported ties with Gilead, Janssen- Cilag, Novartis, Pharmasset, Roche and Vertex...............

An ‘apocalypse moment’ for HCV?

Current therapeutic approaches to treatment of chronic HCV genotype 1 are limited by troublesome side effects, long courses of therapy, drug-drug interactions, and regimens that include pegylated interferon (administered by injection) and a protease inhibitor (administered thrice daily with food). Many patients are ineligible for therapy because of contraindications to the medications.
Furthermore, the current regimens do not have high efficacy in null responders. This has provided the impetus to develop all-oral regimens with better efficacy, improved side-effect profiles, and shorter courses of therapy.
These results of the phase II ELECTRON trial arm testing the all-oral regimen of sofosbuvir (NS5b polymerase inhibitor), ledipasvir (NS5a inhibitor), and weight based ribavirin in patients with chronic HCV genotype 1 (without cirrhosis) add to the recent number of stunning reports describing all oral treatment regimens for chronic HCV.
Such therapeutic approaches offer the promise of tolerable regimens that have outstanding efficacy and may have few or no contraindications to therapy.
It is unclear if patients with cirrhosis will respond as well as noncirrhotic patients did in ELECTRON and whether or not ribavirin is needed; phase III trials are currently underway to address these issues. If the phase II results are replicated in these phase III trials and if the medications are available to all patients who have chronic HCV genotype 1, this type of a regimen could represent the “apocalypse moment” for HCV, when the most common type of HCV worldwide (genotype 1) is largely eliminated.

Steven L. Flamm, M.D., is chief of transplant hepatology and is professor of medicine in the division of gastroenterology and hepatology at Northwestern University Feinberg School of Medicine, Chicago. He disclosed receiving research support from Gilead and serving as an advisor to the company......

Everolimus approved for liver transplant indication

Food and Drug Administration approval of the immunosuppressant drug everolimus has been expanded to include prophylaxis of organ rejection in adults undergoing a liver transplant....

Alpha-fetoprotein useful marker in HCC

Changes in serum alpha-fetoprotein levels over time correlated with the development of hepatocellular carcinoma in hepatitis C patients, wrote Dr. Elliot Lee and his colleagues in the April issue of Clinical Gastroenterology and Hepatology.......

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