Ahead of an critical advisory panel FDA reviewers have advised against approval of a novel drug for acute heart failure from Novartis Novartis. The once highly-promising drug, which received a ”breakthrough therapy” designation from the FDA final yr, was turned down for approval in Europe earlier this year.
On Thursday the FDA’s Cardiovascular and Renal Drugs Advisory Committee will talk about the biologics license application (BLA) for serelaxin injection (proposed trade name Reasanz) from Novartis. The indication is for the improvement of the signs and symptoms of acute heart failure by means of reduction of the fee of worsening of heart failure. (The meeting was originally scheduled for February but was postponed due to climate.) Serelaxin is a recombinant kind of the naturally occurring human hormone relaxin-2, which has been found to assist females adjust to the cardiovascular alterations that arise during pregnancy.
The FDA reviewers raised critical questions and concerns about the pivotal Unwind-AHF trial, which was published in the Lancet in 2012. The reviewers did not increase any security concerns about the drug but stated that “there is insufficient evidence to support the proposed indication.”
Typically, the reviewer notes, the FDA calls for two independent trials to demonstrate a drug’s efficacy. But the Loosen up-AHF trial, the single trial in support of the BLA, was more hampered due to the fact it effectively met only one particular of its two principal endpoints. Further, despite the fact that the trial “was made to assess dyspnea… the proposed declare is to enhance the symptoms of acute heart failure.” Acute heart failure signs other than dyspnea “were not systematically measured in this review,” wrote the reviewer, who went on to then query the reliability and relevance of the dyspnea findings.
The FDA reviewer also cast doubt on the reliability of the surprising locating of a mortality reduction at 180 days in the serelaxin group. Although the result adds self-confidence to the security of the compound, the endpoint was not prespecified and needs to be confirmed in a followup examine before gaining acceptance. The reviewer also considered that additional doubt was raised since the mortality advantage had not been observed at an earlier time point, regardless of the reality that the drug is employed acutely. (Novartis is presently conducting a big outcomes trial to confirm the mortality consequence.)
One particular good note for Novartis is that the roster for Thursday’s panel does not incorporate any of the extremely vocal critics from previous panels, this kind of as Steve Nissen, Sanjay Kaul, or Sidney Wolfe. Even more, speaking on behalf of Novartis will be Milton Packer, an eloquent and persuasive heart failure expert who is also a former chair of the advisory panel.