An FDA advisory panel on Tuesday voted 11-2 that the benefit-risk profile of Correvio Pharma's anti-arrhythmic drug Brinavess (vernakalant) was not adequate to support approval. Correvio is looking to get the therapy cleared in the US for the rapid conversion of recent onset atrial fibrillation in adults, with the FDA scheduled to make its final decision by December 24.
Advisory committee members cited serious safety risks, including hypotension and irregular rhythm in the lower heart chambers, as well as deaths during the trials, echoing similar concerns raised in an FDA staff report earlier this month. "It clearly has benefit, but it does have risk," commented panelist Barry Davis, who voted against Brinavess, adding that "if this were the only drug or treatment around, yes, but there are other options."
However, Correvio CEO Mark Corrigan suggested that "the treatment landscape is currently missing a rapid, efficacious and well-tolerated option to treat patients with recent onset atrial fibrillation and...Brinavess has the potential to fill that unmet medical need." He added "we believe in the strength of the data we presented today for Brinavess."
A marketing application was first filed for Brinavess in 2006 by Astellas, the applicant at the time, but safety concerns eventually led the FDA to put US trials on hold following the death of a patient treated with the drug. The hold prohibiting the administration of vernakalant in clinical studies in the US still remains in place, although the agency accepted a resubmitted filing from Correvio this past July. Meanwhile, the drug has been cleared in 41 countries outside the US, including Canada and in Europe.
According to Correvio, its filing was backed by nine mid- and late-stage clinical trials, as well as "over eight years of post-marketing experience in approximately 50,000 treatment patients worldwide." It also highlighted results from the SPECTRUM post-authorisation safety study conducted in Europe that evaluated 1778 patients across a total of 2009 treatment episodes following administration of Brinavess. Results showed that Brinavess successfully converted 70.2% of patients into normal sinus rhythm, with a median time to conversion of 12 minutes from the start of the first infusion.
Further, the company noted that the cumulative incidence of "health outcomes of interest," defined as significant hypotension, ventricular arrhythmia, atrial flutter or bradycardia, was reported in less than 1% of patients. It added that 28 serious adverse events were reported in 26 of the 1778 patients, with no deaths and no torsades de pointes occurring in the study.
Bloom Burton analyst David Martin estimated that if approved, Brinavess could generate peak US sales of about $150 million by 2024. However, analyst Louise Chen of Cantor Fitzgerald said "the company may consider strategic alternatives for both its US and EU businesses if Brinavess fails to get approval."
Merck & Co. partnered with Correvio, formerly Cardiome Pharma, on the drug back in 2009, even buying up North American rights to the therapy from Astellas a few years later. However, Merck returned global rights to the drug back to Correvio in 2012.
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