Deserted by Astellas and Merck, little Correvio still can't win over FDA panel concerned with its AFib drug's safety
When the FDA spurned Astellas’ pitch for atrial fibrillation drug vernakalant in 2008, regulators made it abundantly clear that it wasn’t the efficacy they had a problem with — two Phase III trials had shown the drug successfully restored 52% of patients’ heartbeat from irregular to normal — but the cardio safety issues for a drug that was to compete with well established, low-risk options. One licensing deal, one clinical hold and several studies later, the chances of approval aren’t looking any better.
Experts on the agency’s Cardiovascular and Renal Drugs Advisory Committee voted 11-2 against approving the drug, dealing a fresh blow to its maker, Correvio Pharma. The panel largely agreed with the FDA internal review that concluded the benefits didn’t outweigh the risks, raising issues such as low blood pressure, arrhythmias in the ventricles and even death.
Correvio, which markets vernakalant as Brinavess in its native Canada, Europe and several other countries, saw its stock $CORV sink below the $1 mark after plummeting 55%.
“We are disappointed with today’s outcome because we believe in the strength of the data we presented today for Brinavess,” CEO Mark Corrigan said in a statement. “The treatment landscape is currently missing a rapid, efficacious and well tolerated option to treat patients with recent onset atrial fibrillation and we believe Brinavess has the potential to fill that unmet medical need.”
It had taken Correvio a decade to get here. In response to the FDA’s rejection in 2008 — which actually followed a refuse-to-file letter two years prior — the biotech, then known as Cardiome, planned and started a new Phase III trial, ACT V. But in 2010, a case of cardiovascular collapse with pulseless electrical activity eventually leading to death triggered a full clinical hold on that study.
Merck, which had licensed rights to the oral version of vernakalant earlier, took over the IV side too for a short while, only to have its application to remove the hold and proposed modifications slammed by regulators. The FDA’s conclusion:
We do not believe that you have identified either a definitive mechanism or root cause of these episodes of vernakalant-induced severe hypotension and/or clinical shock and do not believe that your proposed modifications to the eligibility criteria are adequate to assure that such events will not recur in another trial.
The team that is now Correvio has since conducted multiple animal studies in attempts to understand what’s going on and find a satisfying mitigation strategy — in vain.
“(T)he hold remains in place at this time,” the FDA reviewers noted in their dossier ahead of the adcomm.
Also packaged in the NDA were data from postmarketing studies done outside the US, particularly an EU trial dubbed SPECTRUM, in which the treatment converted 70.2% of AFib patients into normal sinus rhythm, with a median to conversion time of 12 minutes.
But the FDA still noted a total of 174 serious adverse drug reactions and five deaths. And some members of the panel pointed out that given the patients in the trials were at low risk of developing complications, there didn’t seem to be a convincing way to predict who needs special monitoring for safety issues.
“It clearly has benefit but it does have risk,” said Barry Davis of the University of Texas School of Public Health, who voted against the drug, per Reuters. “If this were the only drug or treatment around, yes, but there are other options.”
In addition to medication such as flecainide, dofetilide, propafenone and ibutilide, physicians may also prescribe electrical cardioversion — if they decide an intervention is needed at all.
There is still a possibility — no matter how slim — that the FDA will override the adcomm’s recommendation and OK the drug. The final decision will be handed down by December 24.