- Arca Biopharma Inc. hopes to move forward with late-stage development of its experimental beta blocker despite messy results from a Phase 2b trial that leave questions about the drug's efficacy in treating atrial fibrillation.
- Data released Feb. 26 showed patients treated with Arca's drug, called Gencaro, experienced no greater benefit as those who were administrated Tropol-XL, another beta blocker used off label to prevent atrial fibrillation in patients with heart failure and reduced left ventricular ejection fraction (HFrEF).
- Arca, however, chose to highlight Gencaro's performance in the U.S. patient cohort, in which the drug seemed to reduce the risk of atrial fibrillation recurring compared to Tropol-XL by about 30%. Investors were not impressed by the sub-group analysis, sending shares in the biotech down Monday by $1.15, or 72%.
Arca set up the Phase 2b study to allow for a speedy transition into Phase 3 if interim results suggested a sufficient likelihood of Gencaro (bucindolol hydrochloride) delivering a statistically significant risk reduction in the later-stage trial.
As part of that plan, Arca took the initial Phase 2b data from 267 patients to estimate the so-called predictive probability of success if the transitioned study enrolled a total of 620 participants.
When analyzing data from all 267 patients in the interim analysis, that probability of success worked out to a uninspiring 14% due to the similar benefit seen between the treatment and control arms. Yet when Arca split out only the 127 patients enrolled in the U.S., the company estimated the probability of a Phase 3 success at 61% — higher than the threshold set ahead of time to justify transitioning the study to late stage.
"While we did observe some regional heterogeneity in effectiveness of Gencaro, we believe the treatment response observed in the U.S. population, which represents approximately half of the overall study population, support continued development of Gencaro as a genetically targeted treatment for atrial fibrillation," said company CEO Michael Bristow in a Feb. 26 statement.
Sub-group analyses are often ways of getting around bad data and tend to set companies up for a larger failure in later-stage trials. By the measure set out by Arca, the study was a failure — Gencaro did not show superiority over Tropol-XL (metoprolol).
Despite that, Arca contends it has a shot. The company plans to meet with the Food and Drug Administration in the second quarter to review the results and discuss a potential Phase 3.
While Gencaro is part of the well-known beta blocker class, Arca has targeted the drug specifically at patients with a certain genetic marker based on previous study results. While genetic targeting is common in fields like oncology, cardiovascular drug development has typically focused on broadly defined patient populations.
Even if Arca obtained a green light to proceed to Phase 3, the company would need to raise money to fund further clinical development. As of Dec. 31, Arca reported $11.8 million in cash and equivalents, with another $3.4 million tapped in January through a credit facility. Put together, the $15.2 million should fund operations through the end of the year, Arca said.
Investors don't appear optimistic. After the 72% drop in Arca's share price Monday, the company's current market capitalization sits at just over $5 million, or a third of the company's cash assets.