Wednesday, January 9, 2013

Nucleotide Polymerase Inhibitors - The Search For A Safe Interferon Free Trial

The Search For A Safe Interferon Free Trial

While the HCV community is waiting in the wings for the first all interferon-sparing therapy to make its way down the pipeline and hopefully all the way to FDA approval, the search for a clinical trial without interferon has become a reality.

Searching for clinical trial has always been a daunting task, after the tragic outcome of the Bristol-Myers trial the search has taken on additional concerns and is now being executed with extra caution.

 Bristol-Myers BMS-986094, formerly known as INX-189

In August 2012 -  BMS-986094, formerly known as INX-189 was initially suspended. In the phase II trial (safety issues are studied in phase I clinical trials)  one of 30 patients suffered heart failure while receiving the highest daily dose of the nucleotide polymerase inhibitor. "Nucs" work by targeting polymerase - an enzyme essential for replication of the hepatitis C virus.

Bristol-Myers continues to investigate the safety issues of BMS-986094 with a recent initiated follow up evaluation for people who participated in the phase I trial, here is a link to the observational study.  

***The purpose of this study is to determine the rate of kidney or heart impairment, if any, in subjects who received BMS-986094 (INX-08189) in Phase 1 clinical trials

IDX184 from Idenix

Readers may recall last August when IDX184 from Idenix was put on a partial clinical hold. The U.S. Food and Drug Administration wanted a further review of the drug, citing the serious heart-related adverse event seen in Bristol's drug BMS-986094. Both drugs belong to a promising new class of hepatitis C medicines known as nucleotide polymerase inhibitors which do not require the use of interferon. 

Today Reuters reported;

Idenix says FDA seeks more time to review hepatitis C drug
Wed Jan 9, 2013 12:12pm EST
(Reuters) - Idenix Pharmaceuticals Inc said the U.S. health regulator had informed the company that it would need more time to conduct a safety review of Idenix's hepatitis C drug. 
The company said on its website that the FDA had conveyed the need for additional time earlier this month. (
Idenix said it submitted data to the U.S. Food and Drug Administration in December.
The FDA had placed the drug, IDX184, on a partial clinical hold last August, citing adverse cardiac events seen in rival Bristol-Myers Squibb Co's hepatitis C drug.
Idenix cannot enroll patients in further studies until it gets FDA clearance for the trial design. The company now expects a response in the first quarter of 2013. 
(Reporting by Pallavi Ail in Bangalore; Editing by Roshni Menon)

Published Jan 10 @ Fierce Biotech  
Idenix looks to Plan B as FDA hep C review plods on

The Process - Understanding Clinical Trials - Research - Industry-funded Trials

1- Before searching for a trial understanding each phase of a clinical trial and the protocol is essential. An easy to understand guideline can be found in this HCV Advocate publication, updated September 2012.

2- Research , research, research, begin with this 2013 update: Interferon free therapy with direct acting antivirals for HCV. Additional links can be found on the blog in a series of education-related information that point the reader to relevant data and updates.

HCV Treatment Pipeline Update
12 December 2012 - It is difficult to be anything other than dazzled by astounding cure rates of up to 100% from a multitude of interferon-free hepatitis C virus (HCV) clinical trials presented at the American Association for the Study of Liver Diseases (AASLD) meeting in November 2012. Proof of concept has been established: hepatitis C, a disease that claims more than 350,000 lives annually, can be cured with three months of oral antiviral drugs.

3- Clinical trials are sponsored by either a pharmaceutical company, a federal agency - for example the National Institutes of Health or an individual like a physician or health care provider. Participants should also determine who is sponsoring the clinical trial, recently controversy over industry-supported trials was investigated in this article "Industry sponsorship and research outcome" published in the Dec. 12, 2012 issue of the Cochrane Database of Systematic Reviews. The analysis suggests that drugs and medical devices undergoing clinical trials appear more beneficial when industry sponsored.

Results from clinical studies on drugs and medical devices affect how doctors practice medicine and thereby the treatments offered to patients. However, clinical research is increasingly sponsored by companies that make these products, either because the companies directly perform the studies, or fully or partially fund them. Previous research has found that pharmaceutical industry sponsored studies tend to favor the sponsors’ drugs much more than studies with any other sources of sponsorship. This suggests that industry sponsored studies are biased in favor of the sponsor’s products.

The article can be found here.

In September The New England Journal of Medicine published "A Randomized Study of How Physicians Interpret Research Funding Disclosures" showing that physicians draw clear distinctions in regards to data from industry-supported trials over "the same trials randomly characterized as having NIH funding or having no source of support listed." These privately funded trials were not outright dismissed by the medical community, however, the funding source is looked at with skepticism.

Well-publicized controversies related to industry-funded research may help explain these findings. Reports have emerged of trials that withheld critical data35-37 or that presented positive results while withholding negative results.38,39 Other concerns stem from reports of industry-financed articles that were ghostwritten40 or published primarily as instruments of marketing.41 Physicians' skepticism of industry-funded research may be a response to such trends.

The study is available here.

The Buzz  - Interferon Free Combinations

Hepatitis C - 2013 Interferon Free Combinations

Gilead's lead 'nuc' sofosbuvir anchoring what could become the first interferon-free regimen 

Where To Look For A Clinical Trial

Basic Questions and Answers about Clinical Trials provides regularly updated information about federally and privately supported clinical research in human volunteers. Site gives information about a trial's purpose, who may participate, locations, and phone numbers for more details.

Clinical Trial Updates updated in the last 30 days

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