BioXcel scores another win with reformulated Pfizer sedative, this time in an Alzheimer's symptom
Less than six months after reporting positive Phase III results for its lead program in treating agitation related to schizophrenia and bipolar disorder, small AI biotech BioXcel followed up Tuesday with top-line data in an early stage trial for agitation in dementia and Alzheimer’s disease.
The experimental drug, known as BXCL501, met its primary and secondary endpoints in the higher evaluable dose of a 54-patient Phase Ib/II trial, BioXcel announced, inducing a statistically significant calming effect compared to placebo with no severe or serious side effects. With the data in hand, BioXcel plans to meet with the FDA sometime in the first half of 2021 before launching a late-stage study sometime afterwards.
BioXcel $BTAI shares ticked up by as much as 10% in pre-market trading Tuesday, but after the opening bell were down about 7%.
BXCL501 is a reformulation of Pfizer’s 21-year-old sedation drug Precedex. BioXcel created a dissolving film-based, sublingual version of the drug — think Listerine strips, but placed under the tongue — that patients administered themselves. It essentially produces a calming effect without knocking a patient out and activates the alpha-2 receptor, the pathway through which norepinephrine, among other neuro-chemicals, travels.
Tuesday’s data come from a double-blinded and randomized study conducted entirely within assisted living facilities. Patients in the drug cohorts received either a 30 μg, 60 μg or 90 μg dose, though BioXcel did not measure efficacy or safety in the 90 μg arm due to higher exposure levels. Sixteen patients received the 30-μg dose, 20 took the 60-μg dose, four began the 90-μg dose level and 14 were randomized to the placebo group.
It’s the 60 μg level where BXCL501 differentiated itself from placebo at a significant level. The program hit on all three scales used to measure change in agitation from baseline, the PEC, PAS, and Mod-CMAI. For the PEC, the p-value was p=0.0011, while the other two p-values registered at p<0.0001.
The candidate also showed a rapid onset, BioXcel said, hitting statistical significance compared with placebo in the PEC and PAS just one hour after patients took the film strips, with the company noting it didn’t measure Mod-CMAI after this time period. Calming effects at this dosing level remained at statistically significant levels through eight hours.
BXCL501’s 30-μg dose did not hit statistical significance in any of the three scales, clocking in at p=0.0813 for PEC, p=0.0961 for PAS and p=0.0591 in the Mod-CMAI.
The most common side effect was somnolence, or drowsiness. Half of the 16 patients in the 30-μg cohort self-reported mild drowsiness, while 11 of 20 individuals in the 60-μg cohort did so. There was one case of moderate drowsiness in the 60-μg group as well.
In addition, there were two cases of hypotension in the 60-μg cohort, one mild and one moderate, as well as one case of mild dizziness.
Jefferies analyst Chris Howerton took a positive view of the data, writing that the 60-μg dose appears to “check all the boxes.” The safety at this dose level looked “clean,” though Howerton noted because Precedex is known to be more potent in elderly patients, he wouldn’t be surprised if BioXcel also looked at a 45-μg dose in their pivotal trial.
The issue of a 45-μg dose also came up in a conference call BioXcel held Tuesday morning with investors. CEO Vimal Mehta said that although BioXcel will likely prioritize 60 μg for the Phase III given Tuesday’s top-line results, they aren’t ruling out also testing 45 μg.
Mehta also said on the call that he doesn’t anticipate much disruption in Phase III enrollment related to the ongoing Covid-19 pandemic.
BioXcel is one in a slate of biotechs that has raised millions in recent years on the promise of using artificial intelligence to speed the drug development process. The company filed for a $69 million IPO in 2018 less than a year after being founded, and has aimed to use its tech to find compounds validated to some degree by other companies and repurpose them.
Back in July, BioXcel reported that in two nearly 400-person Phase III trials for bipolar disorder and schizophrenia, the lead drug effectively calmed patients’ agitation.