Friday, August 10, 2012

Weekly HCV Rewind- A Look At Gileads Pan-Genotypic Drug GS-7977

It's Friday again folks, and that means it's time for our HCV weekly rewind, where we take a look back at some relevant news that made the headlines.

Investment commentary, found at The Street, Seeking Alpha, WSJ, Pharmalot, or Bloomberg, to name a few, offers us a backseat look at new hepatitis C agents making their way down the pipeline.

The savvy HCV audience has witnessed big pharma or investors, battle in the unpredictable arena of HCV drugs, as these often promising compounds either make it all the way to FDA approval, or crash and burn. Sadly, it's mostly the latter. However, success is only achieved after FDA approval, which can take an eternity for patients waiting in the wings.

Today, we look at new and revisit previous commentary for investigational hepatitis C drugs making there way through clinical trials, including one particular prediction made in April on BMS-986094 (formerly INX-189) over at The Street.

We know that HCV is curable, although when a cure is within our reach, we just can't seem to get there. With the approval of both Incivek/Telaprevir and Victrelis/Boceprevir we almost made it. However, both drugs are used in combination with peg-IFN and ribavirin which is a problem for patients with pre-existing conditions who aren’t eligible for treatment with interferon. Unfortunately the drugs are not pan-genotypic, and in genotype 1 patients not everyone clears the virus.

The need for all oral, effective and better tolerated agents regardless of genotype, genetic factors, or disease stage are desperately needed. We wait.

For a moment we had a glimmer of hope, when last spring interim data came out for the all oral combination of Gilead's GS-7977 and Bristol-Myers Squibbs' daclatasvir. Finally, a combo without interferon, with a 100% SVR in naive genotype 1 patients. Although, that soon crashed and burned when Gilead did not committed to a Phase III clinical trial, instead the company opted out, and has moved forward in clinical trials with their own drug GS-7977.

This week, Gilead was mentioned over at With a reminder of  the companies high hopes for HCV genotype 1 patients, who previously failed therapy. The company plans on testing their drug combination of GS-7977 and GS-5885 in 2013. If the results are successful, Gilead expects to file for regulatory approval in 2014, and launch the regimen in 2015.  Read the entire article written by R Chandrasekaran.

Gilead announced future trials for GS-7977 and GS-5885 at the end of July, view an article at NATAP with detailed information on the company, conference call, press release, other trial results, slides and all of GS-7977 future trials.

Adam Feuerstein back in April predicted a long wait for Gileads GS-7977/GS-5885 combo, and the possible outcome for Bristol-Myers drug BMS-986094 (formerly INX-189);

A 100% cure rate for genotype 1 patients! Obviously, results can't get better than that. You'd think there'd be a rush to move the combination regimen of daclatasvir and GS-7977 into a larger, confirmatory phase III trial, but you'd be mistaken. Amazingly, this most promising new treatment for hepatitis C patients may actually be discontinued because Bristol and Gilead can't work together. 
Instead, Gilead would prefer to combine GS-7977 with GS-5885, another drug it owns 100% that belongs to the same NS5A inhibitor class as daclatasvir. But a lot of work remains to be done on GS-5885; it may not be as safe or as effective as daclatasvir. It could also take longer for this all-Gilead combination to reach the market, which means Hep C patients in need of treatment will suffer.
Bristol is in a similar situation. Without access to GS-7977, the company is likely to move ahead with a combination of daclatasvir and INX-189, which belongs to the same nucleoside, or "nuc" class of drugs as GS-7977. Bristol acquired INX-189 when it bought Inhibitex for $2 billion earlier this year.  
Bristol still has a lot of work to do with the daclatasvir-INX-189 combination before it can move into phase III studies, which also potentially means Hep C patients will be waiting longer.

At the beginning of August Bristol-Myers Squibb suspended their phase IIb trial of BMS-986094 after a patient in the trial suffered heart failure. The patient was receiving 200 mg of the compound.

At the end of July Gilead announced plans to begin a study of two drugs in a "single pill" for the treatment of HCV.

Gilead announced plans to start a combination study of two drugs in a single pill to treat hepatitis C by the end of the year, putting it on track to request U.S. regulatory approval for the medicine in 2014The company aims for a therapy that "will clearly be a one pill, once daily, maybe a 12 week course," for patients with all different types of hepatitis C, Bischofberger said. "That's our goal. We are very close."

Gileads pan-genotypic trials are exciting, especially in non-genotype 1 patients which are desperately in need of effective therapy. As mentioned above, NATAP has a collection of updates on the company, which also includes the above article from bloomberg.

In closing, I wanted to mention this review from Medscape published at the end of July, which included GS-7977 - Hepatitis C Therapy in Non-genotype 1 Patients: The Near Future.

HCV Drugs In The News
The Rewind - Aug 9 - 3

Aug 9
Achillion HCV drug sovaprevir: 100% Late to the Party
Aug 8
Sovaprevir (Formerly ACH-1625)-Positive SVR4 Results From Phase 2 Study
Gilead Sciences’ Hepatitis C Drug Candidate May Have First Mover Advantage
HCV Genotype 1 Patients -Plan to Initiate Treatment with Already-Available Regimen within the Next Year
Aug 6
Focus on boceprevir - New developments in the management of hepatitis C virus infection
Rethinking Idenix Pharma in Wake of Bristol's Hep C Blow Up
Vaniprevir with peginterferon, ribavirin effectively treated chronic HCV
Curing Chronic Hepatitis C: The New World of Antivirals
Aug 3
Bristol weighs writedown of hepatitis drug

Other News And Research

High-dose Silibinin Rescue Treatment for HCV-infected Patients Showing Suboptimal Virologic Response to Standard Combination Therapy

BREAKING NEWS: Grand Jury Indicts Desai, Nurses on Murder Charge
LAS VEGAS – Dr. Dipak Desai and the two nurse anesthetists charged in the 2007 hepatitis C outbreak case have been indicted for second-degree murder by a Clark County grand jury.

Inovio influenza drugs show promise in Q2, trials ongoing for HIV, Hep C vaccines
Dentist: 'No comment' on investigation
The Denver-area oral surgeon accused of reusing needles and syringes refused comment Thursday on accusations he could have infected his patients with HIV and hepatitis B and C. "I have no comment," Stein said at his door when asked to respond to state health department accusations he reused needles and syringes on at least 8,000 patients.

Update: Two Patients Test Positive in Hepatitis C Investigation
As the investigation continues at hospitals across the country, Hays Medical Center has released an update on its efforts to help patients who may have been infected with hepatitis C by a contract radiology technologist. The man, who was arrested in New Hampshire, was employed at HaysMed in the cardiac catheterization laboratory from May 24, 2010 to September 22, 2010.

So far two patients have tested positive for hepatitis C out of over 400 who Hays Medical Center identified as having a procedure at the cath lab during the time in question. The testing procedure takes time, and not all of the tests are completed, but 311 patients have tested negative for HCV.

Hepatitis C testing begins for 3,300 Exeter Hospital patients

India Offers Rules For Trial Death Compensation

Managing HIV/HCV Coinfection: How Are We Doing?
Drs. Paul Sax and Mark Sulkowski discuss current management strategies for patients with HIV and hepatitis C coinfection and look at how newer regimens might change the treatment landscape. Medscape HIV/AIDS

Height, weight and BMI changes seen in children treated with peginterferon alpha for hepatitis C
In the U.S. an estimated 240,000 children have the HCV antibody and up to 100,000 have chronic HCV (Jonas, 2002). "While HCV in children is typically mild, some cases do progress to cirrhosis and liver cancer," explains lead author Maureen Jonas, Director of the Center for Childhood Liver Disease and Medical Director of the Liver Transplant Program at Boston Children's Hospital in Massachusetts. "Treatment of HCV with peginterferon and ribavirin is approved for young children and offers the most benefit while liver disease is mild. However, there are concerns about the potential side effects of peginterferon therapy in children, which is the focus of our current study."
Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma
We found a different age distribution with non-HCC patients being much younger than HCC patients. There was an increased risk after the age of 42 and a further increase in risk after 60. This is consistent with data on 2166 chronic hepatitis C patients which reported a 15-fold higher risk for HCC in patients over 65 years of age compared to patients in their 20’s [6]. The age peak in our study was between 60 and 69 years. A US study showed an age peak in patients aged 70–74 years for the years 2000 to 2002 [3]. They reported a substantial shift towards younger age with the maximum age being 75–79 in 1991–1993 and 80–84 years in 1982–1984. Our age peak was in line with this trend towards younger age over time.

Delcath Is About To Change The Way We Treat Liver Cancer
The CHEMOSAT® delivery system allows the administration of concentrated regional chemotherapy by isolating the circulatory system of the targeted organ. Once the organ is isolated, the CHEMOSAT® delivery system delivers high doses of chemotherapeutic agents directly to the liver, while limiting systemic exposure and the related side effects by filtering the blood prior to returning it to the patient. The procedure is minimally invasive and repeatable allowing for multiple courses of treatment with chemotherapeutic drugs and the potential for concomitant cancer therapies.

Drug Successfully Halts Fibrosis in Animal Model of Liver Disease
A study published in the online journal Hepatology reports a potential new NADPH oxidase (NOX) inhibitor therapy for liver fibrosis, a scarring process associated with chronic liver disease that can lead to loss of liver function.

Hypertension ups retinopathy risk with HCV treatment
For patients with hepatitis C virus treated with pegylated interferon alpha and ribavirin, retinopathy occurs frequently, especially in those with hypertension, according to a study published in the August issue of Hepatology.

Glucose Abnormalities in Pre-diabetic Chronic Hepatitis C Patients Receiving Peginterferon Plus Ribavirin Therapy
Hepatitis C virus (HCV) infection is the major cause of cirrhosis and hepatocellular carcinoma worldwide.[1, 2] There is robust experimental and clinical data showing the prominent association between chronic HCV (CHC) and type 2 diabetes mellitus (DM).[3–7] For those without known DM, there was a 3.5-folds increase in the prevalence of glucose abnormalities in CHC patients in comparison with that in controls.[8] In addition to its various extrahepatic manifestations [9-12], HCV infection is currently considered to be a diabetogenic factor.

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