Arca AF med back from brink with FDA Phase 3 go-ahead

• Arca Biopharma’s atrial fibrillation medicine, Gencaro, could soon be moving forward again after the company says it received word from the Food and Drug Administration that a single Phase 3 study could support regulatory submission of the drug.
• Based on the FDA’s feedback in an end-of-Phase 2 meeting, Arca plans to submit a special protocol assessment for the trial in the third quarter of 2018. Gencaro, a beta-blocker and vasodilator, has Fast Track Designation as a potential genetically targeted cardiovascular therapy.
• The market doesn’t seem as upbeat as Arca though — after an initial spike in share price this week, the company’s stock fell back below $1 per share.

Gencaro, also known as bucindolol, was originally developed for hypertension and heart failure. But it has had a checkered history. The drug was sidelined after failing to reduce the risk of death by any cause in a 2,708-patient National Institutes of Health-sponsored study.

In 2008, data presented at the Heart Failure Society of America meeting, showed heart failure patients with a particular genetic mutation treated with bucindolol were 38% less likely to die from any cause compared with placebo, as well as 48% less likely to die of heart-related causes, and 44% less likely to be hospitalized for heart failure.

However, in 2009, the Food and Drug Administration rejected the drug for chronic heart failure. The Complete Response Letter requested additional data and also questioned the trial data that had been presented.

According to the FDA, the BEST clinical study — the pivotal Phase 3 trial — did not adequately demonstrate efficacy of Gencaro in reducing all-cause mortality in patients with heart failure. There were questions about the integrity of the BEST data based on the FDA’s audit of certain clinical sites, and about the statistical significance of the pharmacogenetic data used to claim that individual patient response could be predicted by genotype.

In the recently completed GENETIC-AF Phase 2b trial, Gencaro failed to beat out Toprol-XL in the overall study population of heart failure patients in preventing recurrence of atrial fibrillation or all cause mortality. Subgroup analyses conducted by Arca showed a trend toward potential benefit for Gencaro in U.S. patients, but such reviews are often statistically problematic.

In order to fund the Phase 3 development, Arca expects to secure additional financing through a strategic partnership or additional sale of securities.

https://bit.ly/2LN9rDX