Takeda and Orexigen have pulled the plug on a post-marketing study assessing the cardiovascular effects of their obesity pill Contrave, not because of superior efficacy or safety issues but because of premature data disclosure.
Early termination of the Light Study was recommended by the Executive Steering Committee, chaired by Steven Nissen of The Cleveland Clinic, after Orexigen published interim data back in March without consent, compromising the near 9,000-patient trial.
The company, whose management shouldn’t have been in possession of interim data in the first place, said the first 25% of the trial showed that Contrave (buproprion-naltrexone) was linked with a more than 40% reduction in the risk of death, stroke and heart attack, sending its shares rocketing.
This upset the steering committee as it felt there was a danger that doctors were prescribing Contrave based on ‘unreliable’ information. And in fact, subsequent analysis including the next portion of patients - 50% of the trial - indeed shows the purported CV benefit to be dramatically reduced.
No benefit, no harm
“These results show neither benefit nor harm for patients taking the drug, but are consistent with the requirement by the FDA that the Light Trial demonstrate an absence of a doubling of cardiovascular risk for patients taking the drug,” said Nissen.
However, “the inconsistency of effects on cardiovascular outcomes between the first 25% and the second 25% of the Light Study clearly illustrates the risks inherent in pre-judgment of clinical trial results based upon an interim analysis and demonstrate why interim results should remain confidential during any ongoing trial.”
Orexigen now has to start a whole new CV outcomes study, as required by the FDA under its approval of Contrave, which is now set to complete in 2022.