www.hivandhepatitis.com

Hepatitis C Candidate BMS-986094 Halted after Death, IDX19368 Gets Clinical Hold

Bristol-Myers Squibb (BMS) announced last week that it has discontinued development of its experimental hepatitis C virus (HCV) NS5B nucleotide polymerase inhibitor BMS-986094 (formerly known as INX-189) due to serious adverse events including 1 death. In related news, the Food and Drug Administration (FDA) placed a clinical hold on another drug in the same class -- Idenix's IDX19368 -- due to concerns about BMS-986094.

BMS-986094

As previously reported, BMS announced early this month that it was halting development of BMS-986094 to protect patients after identification of a "serious safety issue" in a Phase 2 clinical trial.

According to further information released last week, several study participants experienced serious cardiac- and kidney-related adverse events; 9 people have been hospitalized to date. Within this group, 1 participant died and 2 remain in the hospital.

"While the cause of these unexpected events, which involve heart and kidney toxicity, has not been definitively established, the company has determined that it is in the best interest of patients to halt development of BMS-986094," BMS stated in a press release.

The company added that it is "working in close collaboration with the FDA and clinical study investigators to conduct ongoing, comprehensive assessments and close follow-up of all BMS-986094 study patients."

"In the interest of all patients participating in hepatitis C clinical studies, and in cooperation with the FDA, we will make relevant information on BMS-986094 available to inform the development of other investigational compounds to treat hepatitis C," said BMS Executive Vice President and Chief Scientific Officer Elliott Sigal. "We will also work expeditiously to share the results of our further investigations more broadly in the medical and scientific community."

IDX19368

Idenix Pharmaceuticals announced on August 27 that it received verbal notice from the FDA that the agency placed a clinical hold on IDX19368 -- which so far no patients have received -- another next-generation nucleotide HCV polymerase inhibitor.

"Based on our discussions with the FDA, we understand the clinical hold is a precautionary decision made by the FDA in light of the adverse events seen with BMS-986094," said Idenix President and CEO Ron Renaud in a company press release issued this week.

This news follows an announcement on August 16 about a partial clinical hold on IDX184, the company's lead investigational nucleotide polymerase inhibitor. The FDA previously suspended clinical trials of IDX184 in September 2010 due to concerns about liver toxicity among participants who took the drug in combination with IDX320, an experimental HCV protease inhibitor. The hold on IDX184 was lifted in full in February of this year, after further investigation indicated that the liver problems were probably due to IDX320.

"Both
IDX184 and IDX19368 fall into the same broader class of NS5B inhibitors, and share the same active metabolite as BMS-986094," Renaud explained.
"However, there are many attributes of our compounds, particularly the prodrug approach, that we believe favorably differentiate the toxicity profiles from that of BMS-986094."

As part of the earlier clinical hold, the FDA requested additional cardiac testing of trial participants who took IDX184. More than 50 patients have been scheduled for echocardiograms, and tests performed on a small number of these people to date have been normal, according to the company.

8/30/12

Sources

Bristol-Myers Squibb. Bristol-Myers Squibb Discontinues Development of BMS-986094, an Investigational NS5B Nucleotide for the Treatment of Hepatitis C. Press release. August 23, 2012.

Idenix Pharmaceuticals. IDX19368, for Which Idenix Has Submitted an IND Application, Has Been Placed on Clinical Hold by FDA. Press release. August 27, 2012.