Drug "re-innovation" specialist Bioxcel Therapeutics Inc. is gearing up to discuss a pivotal phase III trial for BXCL-501 with the FDA after top-line results of a phase Ib study showed it reduced schizophrenia-associated agitation while calming trial participants without excessive sedation. H.C. Wainwright & Co. analyst Raghuram Selvaraju called the results "highly favorable" and suggested the drug, a sublingual-formulated version of dexmedetomidine, could reach market as soon as 2021.

Bioxcel CEO and founder Vimal Mehta told BioWorld "everything is falling into place" as the company approaches discussions with the FDA around skipping a previously planned study to characterize variability of response to the medicine. Though once characterized as critical to powering the phase III, data from the phase Ib were "so robust, with multiple doses achieving statistical significance, we decided not to pursue that path and to go directly to the pivotal trial," he said.

With FDA fast track status for BXCL-501, which allows for frequent meetings with the regulator to discuss development plans, Bioxcel's team should be able to determine the agency's stance relatively quickly. The phase Ib data "gave us everything that we were hoping to get in the next step," Mehta said, expressing confidence that the agency would be satisfied with allowing it to move ahead based on the data collected to date.

Once ready, Bioxcel will seek the FDA's approval through the 505(b)(2) regulatory pathway, which only specifies types of studies that need to be done rather than specific trials. That means that in addition to data it has gathered on its own, the company will be able to draw on years of research behind the sedative Precedex (dexmedetomidine, Maruishi Pharmaceutical Co. Ltd., Orion Corp. and Hospira Inc.), an injectable form of the alpha-2 adrenergic receptor agonist.

Phase Ib results

Bioxcel's randomized phase Ib study was double-blind and placebo-controlled. It evaluated multiple doses of BXCL-501 for the acute treatment of agitation in 135 patients with moderate to severe schizophrenia and was the first test for the company's film delivery system in that patient population. Investigators observed a reduction in agitation and rapid calming without excessive sedation at two hours and earlier time points, the company said.

Investigators tested 80-mcg, 120-mcg and 180-mcg doses of the minty green sublingual film-delivered drug, finding statistically significant reductions in PEC (Positive and Negative Syndrome Scale, Excitatory Component) scores of -7.1, -9.2 and -10.8, respectively vs. -4.5 for placebo at two hours.

The drug also performed well on a secondary measure of calming conducted using another metric, ACES (Agitation-Calmness Evaluation Scale), with statistical significance for calming at two hours compared to placebo in the three highest doses evaluated.

Company managers now anticipate enrolling about 600 to 700 patients, split roughly between those with schizophrenia and bipolar disorder, for the pivotal trial. That trial, which could take as little as four to six months to run, will be designed to measure reduction in PEC at two hours as the primary endpoint.

During a conference call held to discuss the phase Ib results, Mehta described agitation as a costly phenomenon associated with multiple neuropsychiatric conditions, including schizophrenia and bipolar disorder. The company is also investigating BXCL-501 for the treatment of agitated dementia, opioid withdrawal symptoms and hyperactive delirium.

Mehta said company research indicates that about 8.3 million people in the U.S. suffer bouts of agitation each year. Bioxcel's team is targeting patients with mild to moderate forms of the condition, accounting for about 3 million to 5 million patients including schizophrenia, bipolar, dementia and delirium.

Bioxcel uses artificial intelligence to repurpose existing compounds for new uses. The company raised net proceeds of $54 million in its March 2018 IPO. It had about $36.3 million in cash and cash equivalents remaining as of March 31. (See BioWorld, Feb. 14, 2018.)

Despite an initial bounce, Bioxcel shares (NASDAQ:BTAI) remained relatively flat on Monday, closing at $10.60, up less than 1%.

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