By Peter Loftus
A regimen containing an experimental Merck & Co. (>> Merck & Co., Inc.) drug suppressed the hepatitis C virus in most patients in a new clinical trial, and appears to be more potent than the company's Victrelis treatment.
The mid-stage study included the injectable drug interferon that Merck and its rivals hope to drop from future regimens. Merck now plans to conduct new studies of its drug, MK-5172, as part of a potential all-oral hepatitis C regimen that eliminates interferon, which can be difficult for patients to tolerate.
Merck is among a pack of drug companies--including Gilead Sciences Inc. (>> Gilead Sciences, Inc.) and Abbott Laboratories (>> Abbott Laboratories)--racing to tap what's expected to be a multibillion-dollar market for all-oral regimens. Current standard therapies, including Merck's Victrelis, are typically given with interferon.
Hepatitis C is a viral disease that attacks the liver, and is believed to afflict about 180 million people world-wide, with more than four million in the U.S., according to the National Institute of Allergy and Infectious Diseases. At-risk groups include people who had blood transfusions before 1992, when a screening test for the virus was developed.
Merck is presenting clinical data for MK-5172 at the annual meeting of the American Association for the Study of Liver Diseases in Boston, which began Friday.
MK-5172 is a so-called protease inhibitor, the same class of drug as Victrelis, which went on sale last year and generated $387 million in sales for the first nine months of 2012. But MK-5172 is designed to be more potent and to carry a higher barrier to treatment resistance than Victrelis, said Eliav Barr, vice president of infectious diseases with Merck's research arm.
In a phase 2, or mid-stage, clinical trial of about 330 patients with hepatitis C, patients were given various dose levels of MK-5172 in combination with the drugs ribavirin and interferon for 12 weeks. One group of patients received Victrelis plus ribavirin and interferon--which is now a standard treatment.
The study found that 96% of patients who received the 100-milligram dose of MK-5172 had sustained virologic response 12 weeks after treatment ended, the highest response rate of the various treatment groups. Sustained virologic response is roughly equivalent to being virus-free or having nearly undetectable viral levels.
By comparison, some 54% of patients in the Victrelis group achieved sustained virologic response at 12 weeks. This is lower than what prior, larger studies have shown for Victrelis. In prior studies, the drug led to sustained virologic response in about two-thirds of patients at 24 weeks after treatment.
Higher doses of MK-5172 were associated with liver toxicities, said Dr. Barr.
Because the study contained interferon, additional studies are needed to test whether MK-5172 is efficacious without interferon.
Merck plans to conduct phase 2 studies of MK-5172 in combination with another experimental oral drug, MK-8742, plus ribavirin, which is also an oral drug. If testing goes well, Merck may consider removing ribavirin from the regimen and pursuing a combination of MK-5172 and MK-8742, he said. Ideally, they could be combined in a once-daily tablet.
"We're looking for something highly efficacious, short duration, well-tolerated and all-oral," he said.
Dr. Barr declined to provide a timeline for when Merck might be in a position to submit a new hepatitis C regimen for regulatory approval.
Analysts generally view Gilead as leading the all-oral hepatitis C race, with Abbott Labs and Bristol-Myers Squibb Co. (>> Bristol Myers Squibb Co.) also still in the hunt. Bristol experienced a setback this summer when one of its hepatitis C compounds failed because of safety issues, but it has others in the pipeline. These companies are expected to present additional, updated data on their drugs at the AASLD meeting.
Abbott Labs reported some results for its hepatitis C drugs in October. Updated results show that a combination of three experimental Abbott drugs--ABT-450 combined with the boosting agent ritonavir, ABT-267 and ABT-333--plus ribavirin led to 12-week sustained virologic response rates of 97% in patients who hadn't received prior treatment, and 93% in patients who had received prior treatment.
In addition, a group of patients who received the Abbott drugs without ribavirin had a sustained virologic response rate of 87% at 12 weeks. These patients hadn't received prior treatment.
"We think the efficacy is a very exciting result to see," said Barry Bernstein, head of hepatitis C development at Abbott.
About 1% of patients discontinued study treatment due to adverse events, Abbott said.
Abbott has begun phase 3, or late-stage testing, of its hepatitis C regimen, with and without ribavirin. The company expects it may secure regulatory approval for a regimen by early 2015 if further testing is positive.
Write to Peter Loftus at [email protected]
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