A second large, randomized clinical trial for assessing CV safety outcomes of naltrexone-bupropion (Contrave, Orexigen/Takeda Pharmaceuticals) has been halted prematurely—this time due to between-company politics.
The phase 4, Takeda-sponsored CONVENE trial was started December 18, 2015 to assess major adverse cardiovascular events (MACE), including CV death, nonfatal MI, and nonfatal stroke, in obese patients with CV disease after 6 years of follow-up. Although the investigators had hoped to include 8800 patients, enrollment was stopped last week—soon after the announcement that Takeda was selling its US rights to the drug to Orexigen.
As reported by heartwire from Medscape, another large Contrave study was stopped prematurely a year ago. The LIGHT trial was also supposed to assess CV safety, but early disclosure of the trial results caused its executive steering committee to put a halt to it in March 2015. Because of this leak, CONVENE was created to give a fresh eye to safety issues for the obesity-treating drug.
However, with the transfer of the Contrave new drug application and investigational new drug exemption, Orexigen took over postmarketing development programs in the US, as well as for Mysimba in Europe, and this included taking on CONVENE—which the company said was too complicated to complete.
"In order for this trial to have continued under Orexigen sponsorship, a significant number of operational details would require reinitiation," said the pharmaceutical company in a statement sent to heartwire . "Based on the amount of time that it will take to effectuate these changes and the very limited number of subjects enrolled in the CONVENE study, Orexigen is terminating the study."
Trial chair Dr Steven Nissen (Cleveland Clinic, OH) reiterated to heartwire that the number of patients enrolled was very few. "But keep in mind that's it's the pretrial efforts, writing the protocol, etc, that takes quite a bit of time. All that effort of designing a trial and getting it up and running . . . that work will need to start over."
The FDA approved the drug in September 2014 by a pathway created to fast-track meds so they could be accessed while safety evaluations continue.
Orexigen reported that it has already notified the FDA of the CONVENE changes and plans on conducting an all-new CV outcomes trial for the drug "to satisfy the FDA's postmarketing requirements."
However, Nissen isn't optimistic that this will be done anytime soon. "In my view, it will be very difficult for them to initiate a new trial and meet [these] requirements. But they have taken on that responsibility. They have the right to do what they want to do, although they will be held accountable by the agency."
He added that it's been nearly a year and a half since the drug was approved, "and there is now no ongoing trial" to meet the postmarketing requirement.
Overall, "it's been a very disappointing saga," said Nissen. "We set out to determine whether the drug would be safe from a cardiovascular perspective. But now two separate trials have been terminated under irregular circumstances."
Heartwire from Medscape © 2016 Medscape, LLC
Cite this: Orexigen Orders Second Contrave CV Safety Trial Halted - Medscape - Apr 13, 2016.