BMS halts development of Phase 1 anti-HCV nuc, BMS-986094...

Posted 8/2/12 on MedPage Today.com. BMS halts development of its investigational nuc BMS-986094 for treatment of chronic HCV after one of the patients the 200mg arm of the  phase 1 trial suffered heart failure. It is unknown at time of publishing whether the drug was directly linked to the drug and all patients involved with the trial are undergoing full assessment.  This effectively makes GS-7977, Gilead's nucleotide analog one of the only nucs currently in advanced development unscathed by toxicity and certainly adds to it's luster, at least in the short term. 

Safety Issue Halts Study of BMS HCV Drug

By Michael Smith, North American Correspondent, MedPage Today
Published: August 02, 2012

Bristol-Myers Squibb has suspended treatment "to protect patient safety" in a phase IIb trial of an investigational oral drug for hepatitis C.

A spokeswoman for the company said the decision was made after one of the patients getting 200 mg of the compound, dubbed BMS-986094, suffered heart failure.

Bristol-Myers Squibb is not giving further details on the patient's condition, according to Cristi Barnett, the company's associate director of public affairs.

In an email to MedPage Today, Barnett said it's still not clear what caused the heart failure or whether it's related to the study drug. To try to clarify the issue, BMS is doing "an immediate assessment of all patients receiving 094 at any dose," Barnett said.

"This assessment includes full physical exams and histories, and cardio ECHO imaging and ECGs for all patients," Barnett said. "Any clinically significant cardiac ECHO abnormality will then be reviewed by a consulting cardiologist as soon as possible."

The drug is a nucleotide NS5B polymerase inhibitor and was acquired by the company when it paid $2.5 billion in January to purchase Inhibitex, the original developer. It was first known as INX-08189.

It's one of several under development -- both Gilead Sciences of Foster City, Calif., and Vertex Pharmaceuticals of Cambridge, Mass., have competitors in the field.

The range of potential treatments for the virus, blamed for about 15,000 deaths annually in the U.S., has been expanding dramatically with the recent development of so-called direct-acting agents.

Two HCV protease inhibitors -- telaprevir (Incivek) and boceprevir (Victrelis) -- are already on the market, but they are indicated for use with pegylated interferon-alfa and ribavirin, which aim at stimulating the immune system rather than targeting the virus directly.

The goal has been to develop all-oral combinations of direct-acting agents that would eliminate the need to use interferon and ribavirin.

BMS-986094 was being tested in a two-part dose-ranging study, dubbed AI472-003, among patients with HCV genotypes 2 or 3 who had not been previously treated. Genotypes 2 and 3 are regarded as being easier to cure than genotype 1.

The first part of the 12-week study was double-blinded and included 90 patients in four treatment arms. In the comparator arm, patients were treated with pegylated interferon-alfa and ribavirin, plus an oral placebo.

In the remaining arms, patients got interferon and ribavirin plus 25, 50, or 100 mg of BMS-986094.

The second part of the study, planned to include 120 patients, was open label for 12 weeks and had five arms.

In two arms, patients took either 100 or 200 mg of BMS-986094, combined with ribavirin. In two others, they took the same doses of the drug, this time combined with daclatasvir, the company's investigational NS5A replication complex inhibitor.

Finally, in the fifth arm, they took 50 mg of BMS-986094 and both daclatasvir and ribavirin.