Orexigen puts Contrave at risk by stopping yet another heart study

stop sign

Orexigen has already lost its Contrave marketing partner and poured good money down the drain by fumbling a safety trial on the drug. Now, its second attempt at that cardiovascular trial is kaput.

As CardioBrief reports, Orexigen has terminated enrollment in the Convene trial, designed to fulfill the FDA’s mandate for a cardiovascular outcomes study. The company notified trial sites of the halt and stopped enrolling new patients.

The trial news comes a month after partner Takeda canned its marketing deal, leaving Orexigen to fly solo. The Japanese drugmaker had helped launch the med, with 900 reps on the ground and its marketing expertise at work, but though Contrave had managed to gain a foothold in the tough obesity drug market, it still wasn’t bringing in much in the way of sales. It delivered just $53 million in 2015 revenue, and Takeda was still on the hook for $50 million in marketing spend this year and next. 

Orexigen says it’s going to start over on that CV outcomes trial now that Takeda is no longer involved. Re-starting the Convene trial under Orexigen’s control would have been too cumbersome and time consuming, the company told CardioBrief in a statement, so it decided to terminate the study instead.

“The company expects to make certain changes to optimize the Contrave/Mysimba post-marketing requirement studies for the company's global needs,” the company told CardioBrief, adding that it has “reaffirmed its commitment” to meeting the FDA’s post-marketing trial requirements.

But as CardioBrief notes, the FDA could well take action against Contrave, given that its approval depended on that CV outcomes trial. Former FDA Commissioner Joshua Sharfstein has already called on the agency to put new restrictions on its use until more is known about its heart safety.

Contrave hit the market for next-gen obesity meds behind Arena Pharmaceuticals’ Belviq and Vivus’ Qsymia. But the Orexigen drug was seen as a potential first-place contender because of stronger study data. The FDA’s required outcomes trial, dubbed Light, was already in process.

The trouble began last March, when Orexigen included interim data from that trial--which was supposed to be private--in a patent application. The early data, analyzed when the trial was just 25% complete, appeared to show that Contrave not only was safe for the heart, but might deliver some cardiovascular benefits.

Analysts cheered, but the FDA cracked down. With data gone public early, the trial was compromised, the agency said. By May, Takeda and Orexigen had shut down the 9,000-patient trial. To make matters worse, researchers released data from the trial’s halfway point, and the early CV benefits had completely disappeared.

Understandably, Takeda wasn’t happy--and it threatened to walk on the marketing deal then. It stuck around only after putting Orexigen on the hook for a replacement study, projected to cost up to $250 million.

Now, of course, Takeda has changed its mind and decided to bag the drug. Data from the Light trial hit the Journal of the American Medical Association, where researchers said Contrave not only didn’t deliver CV benefits--it might not even be safe for long-term use in obesity. Last month, Sharfstein called on the agency to slap new limits on Contrave as a counter to the “misleading” information executives had touted last year.

After Takeda handed back U.S. rights to Contrave, Orexigen said it would pursue a “more focused” launch strategy with a “modestly sized” sales force to target the most active prescribers of obesity meds. Valeant signed on to market the drug in Europe, where it goes by the name Mysimba, but that company has problems of its own, with its marketing techniques in question and no guarantee that it can develop effective new ones.

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