UPDATE: Takeda threatens to break off Orexigen collab after Contrave data drama
UPDATE: Orexigen CEO Mike Narachi responded to the Cleveland Clinic's unauthorized data dump and study overseer Dr. Steven Nissen's claims that the company had "misled" patients and investors on its obesity medication Contrave's heart benefits during the Bank of America Merrill Lynch Healthcare Conference on Tuesday.
"Contrary to allegations cited today by a journalist, Orexigen has never misled patients," said Narachi in a statement, referring to Forbes' Matt Herper. "At the time of the patent issuance in March, we stated plainly and clearly that the effect of Contrave on CV morbidity and mortality has not been established and that a larger number of MACE are required to precisely determine the effect of Contrave on CV outcomes." The data released by the Cleveland Clinic showed the ostensible heart benefits vanished over the long term, as evidenced by a 50% interim analysis.
The company also revealed that Takeda had begun a dispute resolution procedure with Orexigen and is asking the firm to pay the full $200 million to run a second trial, as has been demanded by the FDA.
"Takeda sent a dispute letter to Orexigen on May 12 whereby Takeda seeks termination of its collaboration agreement with Orexigen based on Orexigen’s material breach of the agreement," said Takeda spokesperson Sandy Rodriguez in an e-mail to Bloomberg. "Takeda is working closely with Orexigen to try to resolve the situation and avoid termination of the agreement."
- Forbes' Matt Herper reports that Dr. Steven Nissen, the chair of cardiology at the Cleveland Clinic and the doctor who oversaw a 9,000-patient study on the obesity med Contrave, is claiming that the drug's maker, Orexigen Therapeutics, misled patients and investors about the therapy and that he has the data to prove it.
- Orexigen got into hot water in March after prematurely releasing data implying that Contrave significantly reduced adverse CVD events like heart attacks and strokes (to the tune of 41%)—particularly staggering for an obesity drug. Officials overseeing the trial and others from the FDA slammed the unauthorized data release and said the results were "unreliable" and "misleading."
- The company and its partner, Takeda, have faced enormous pressure to release the full trial data. In fact, the executive committee overseeing the trial voted unanimously in late March to halt it midway through and disclose the results—but Orexigen stalled, sending out a press release on Tuesday that only said the trial had been stopped. Nissen and the Cleveland Clinic have responded by releasing the full trial data without permission from Orexigen/Takeda. And it shows that the ostensible heart benefit vanishes completely over the long-term. Takeda is now reportedly asking Orexigen to bear the full cost of running a second trial for Contrave, and some in the industry are speculating whether or not the FDA will yank the drug's approval.
Orexigen's Contrave data debacle has taken a dramatic turn. For a more detailed history of this saga, read Herper's piece on the FDA's deal with Orexigen (and how the company defied it).
The data that the Cleveland Clinic released today shows nothing approaching the sunny results initially touted by Orexigen. In fact, the placebo-Contrave gap in adverse CVD events dwindled to a statistically insignificant 12%, versus the staggering 41% that the company selectively leaked in March. In fact, a closer look at the data shows that many of the patients enjoying the ostensible benefits were actually no longer taking Contrave at all.
"Patients were misled, investors were misled," Nissen told Forbes. "It is so critically important that investors and other people understand why early data in a trial are unreliable or unstable."
Orexigen and Takeda have yet to respond to the Cleveland Clinic's data dump (updated above). As of Wednesday morning, Orexigen shares have plummeted nearly 20%.