In the heat of the race for an interferon-free treatment for hepatitis C virus (HCV), Bristol-Myers Squibb Co. (BMS) stumbled over a serious safety issue in a Phase IIb trial of BMS-986094.
One of the 30 subjects enrolled in the highest dosing arm of the open-label trial experienced heart failure, causing BMS to suspend the trial while it evaluates all the subjects and the data.
The serious adverse event was seen in an arm of the trial combining 200 mg of the nucleotide polymerase inhibitor with BMS' daclatasvir, company spokeswoman Cristi Barnett told BioWorld Today. Daclatasvir has performed well in other HCV combination therapies. (See BioWorld Today, July 30, 2012.)
Until it assesses the data and determines whether the heart failure was related to the study drug, BMS is not sure what the future holds for BMS-986094, Barnett said. The drug, formerly known as INX-189, spurred BMS' $2.5 billion buyout of Inhibitex Inc. earlier this year. (See BioWorld Today, Jan. 10, 2012.)
No serious cardiovascular events were seen in the first part of the Phase II study, Barnett said. The double-blind, placebo-controlled Phase IIa trial evaluated three doses 25 mg, 50 mg and 100 mg of BMS-986094 in combination with the HCV standard of care, peginterferon alfa-2a and ribavirin.
Two arms of the interferon-free Phase IIb trial were testing the 200-mg dose of BMS-986094. Besides the arm with daclatasvir, the 200-mg dose was being evaluated in combination with ribavirin. The other arms of the trial were testing 100 mg of the study drug with ribavirin, 100 mg with daclatasvir and 50 mg of BMS-986094 with both ribavirin and daclatasvir. The trial was designed to enroll 120 patients, but it wasn't fully enrolled yet, Barnett said.
The setback isn't pushing BMS out of the HCV race. Seeing the space as a viable market, the company will continue to move its other candidates forward in a multipronged approach, Barnett said. But the company (NYSE:BMY) got a bit bruised on the news, with its shares losing $3.05, or 8.6 percent.
After a day of heavy trading with a volume more than five times higher than the 7 million shares traded Wednesday BMS closed Thursday at $32.55.
Of course, allegations of an insider trading scandal probably didn't help. Robert Ramnarine, director of pensions and savings investments at the Princeton, N.J.-based BMS, was arrested this week by the FBI on charges of insider trading for buying stock options in three drugmakers BMS was looking to acquire.
BMS' possible stumble in HCV leaves frontrunner Gilead Sciences Inc. well ahead of the pack as it heads toward the finish line. Gilead's GS-7977, an NS5B inhibitor, is already in Phase III trials, and a Phase III trial of GS-7977 in combination with GS-5885 is likely to begin in the fourth quarter. "We expect Gilead to be both the first company to market with an all-oral combination regimen and the only one with a co-formulated [nucleotide plus] NS5A combination," Piper Jaffray analyst M. Ian Somaiya said in an investor note.
The irony is that Gilead, of Foster City, Calif., acquired GS-7977 as part of its $11 billion buyout last year of Pharmasset Inc., a company BMS had targeted for acquisition. In fact, Pharmasset was one of the three drugmakers Ramnarine bought stock in. The other two were ZymoGenetics Inc. and Amylin Pharmaceuticals Inc. (See BioWorld Today, Nov. 22, 2011.)
Shares of Gilead (NASDAQ:GILD) hit a high of $58.84 Thursday, up nearly 10 percent from Wednesday's close of $53.63. Like BMS, Gilead saw more than a fivefold increase in its trading. It closed Thursday at $57.29, up 6.8 percent.
Gilead isn't the only HCV competitor that may come out ahead because of BMS' falter. If BMS-986094 is permanently sidelined, Abbott could become a stronger challenger, RBC Capital Markets analyst Glenn Novarro said. Its Phase II CO-PILOT trial demonstrated more than 90 percent cure rates with a combination of ABT-450, ABT-333 and ribavirin. The company also is studying several other HCV combinations, including some without ribavirin. (See BioWorld Today, April 20, 2012.)