Last year, Anthera Pharmaceuticals ($ANTH) pulled the plug on its lead drug after the cardiovascular disease treatment ran into some insurmountable efficacy problems in Phase III. What the company didn't mention, however, is that the now-discarded varespladib actually increased patients' risks of heart attack and stroke, and the trial's lead investigator said Anthera dragged its feet in releasing the data.
The study, finally unveiled at this week's American Heart Association meeting, found varespladib to have little benefit for patients with acute coronary syndrome, instead boosting their risk of heart attack by about 65%. Its primary endpoint--a composite of sudden death, heart attack, stroke and unstable angina--occurred in 5.1% of patients on placebo and 6.1% of those taking varespladib. The drug's effect on heart attack risk was even more significant, with 3.2% of patients in the treatment arm suffering infarctions compared to 2.2% taking placebo.
And, as Medscape reports, lead investigator Stephen Nicholls said Anthera is to blame for the 18-month delay between wrap and publication, as the company refused to turn over the final database to researchers "despite multiple requests and what was a contractual obligation."
"In fact, more than a year after the cessation of this study, it was only at that point that we received the database, when the sponsor's license of the compound expired and the license actually returned to the original developer of the compound," Nicholls told Medscape. Anthera also failed to follow up with all of the patients in the study at 6 months, breaking trial protocol and ignoring a letter from investigators, he said.
An Anthera spokesman told FierceBiotech that the company doesn't dispute the study's results but has no comment on Nicholls' claims about prolonging its publication.
Varespladib is designed to inhibit the body's production of the enzyme sPLA2, which promotes the vascular inflammation tied to arterial clogging. Just what went wrong in the study remains a mystery to investigators, who remain unsure whether the spike in heart attack risk is due to varespladib alone or a pitfall of any and all sPLA2 inhibitions. In addition to spurring cardiovascular inflammation, the enzyme is known to have a few protective effects, the researchers said.
Just last week, GlaxoSmithKline ($GSK) hit a major Phase III roadblock with a similar therapy, finding that its blockbuster hopeful darapladib had no significant effect on heart attack, stroke or death. That drug targets the enzyme Lp-PLA2, also linked with the development of atherosclerosis.