Promising topline results from part 1 of pivotal SERENITY III trial of BXCL 501 for at-home use in acute treatment of agitation in bipolar disorders or schizophrenia

These results are expected to enable the initiation of Part 2 for at-home use. BXCL 501 would represent the first-ever FDA approved therapy for at-home use in this indication, if approved.

SERENITY III is a two-part, double-blinded, placebo-controlled pivotal study designed to evaluate BXCL 501 in acutely agitated adult patients with bipolar disorders or schizophrenia for at-home use. Part 1 was similar to SERENITY I and II in design and assessed the efficacy and safety of a 60mcg dose using the same primary and secondary endpoints with patients in a monitored medical setting, as surrogates for the home setting. Patients enrolled in Part I were expected to have a relatively higher level of agitation than the home-based patient population expected to be enrolled in Part 2. Patients in Part 1 were evaluated with half (60mcg) of the already-approved 120mcg dose (Igalmi) to enhance safety for the targeted at-home setting.

“We are pleased with the outcome and progression of our land-and-expand strategy, which we believe moves us closer to addressing up to an additional 23 million annual agitation episodes in bipolar disorder and schizophrenia patients in the at-home setting. This would potentially more than double our current market opportunity, if approved. Treatment in the early stages of agitation at home could significantly benefit patients, caregivers, and hospital systems by reducing the need for emergency room visits and associated treatment costs,” said Vimal Mehta, CEO of BioXcel Therapeutics. “We believe the entirety of BXCL 501’s clinical dataset generated, along with our upcoming Alzheimer’s-related agitation milestones, could transform the agitation landscape for a broad spectrum of neuropsychiatric patients.”

Clinically meaningful efficacy results were observed with half (60mcg) of the lowest approved dose of Igalmi. In addition, greater than 50% PEC response rate was achieved, with responder rate dose-proportionally consistent with those observed in SERENITY I and II trials. Although the primary efficacy endpoint was not statistically significant at 2 hours (p=0.077), BXCL 501 separated from placebo at 4 hours (p=0.049).

The study results suggested a broad safety margin with no reported serious adverse events (SAEs). The principal finding relates to the favorable safety results relative to those observed in studies evaluating the higher approved doses (120mcg and 180mcg). These data provide a clear path for initiating SERENITY III Part 2, to pursue approval in the at-home setting. Alignment has been obtained with the FDA for 60mcg and repeat dosing for Part 2.

“Overall, the 60mcg dose appears to be well-tolerated with safety results comparable to placebo, which is favorable for testing in the at-home setting. In the real world, physicians adapt their treatment approach based on both the patient and the underlying situation,” said Dr. John Krystal, M.D., the Robert L. McNeil, Jr. Professor of Translational Research and Chair of the Department of Psychiatry at Yale School of Medicine. “Therefore, I believe the strategy for Part 2 of the trial is well-suited to evaluate the value of BXCL501 for treating the continuum of agitation occurring at home.”

Summary of Topline Results from Part 1 of SERENITY III; i. Efficacy Results: For the primary endpoint, at 2 hours post-dose, the change in PEC differed from that with placebo, but did not reach statistical significance, with a p-value of 0.077. At 4 hours post-dose, the p-value was 0.049. 52% were PEC responders by 2 hours post-dose (p = 0.019 versus placebo). The proportion responding was greater than with placebo as early as 1 hour (p = 0.035) and remained so through 4 hours. The proportion responding by CGI-I assessment (achieving a score of 1 or 2, ‘Very much improved’ or ‘Much improved’, respectively) was greater than with placebo at 2 hours post dose (p = 0.039). ii. Safety and Tolerability Results: The 60mcg dose was well tolerated and there were no reported serious adverse events. All adverse events were reported as mild to moderate, with none of severe intensity. No adverse events required medical intervention or monitoring. The most commonly reported adverse event was somnolence, defined as feeling drowsy, sleepy, fatigued, or sluggish, which occurred in 13% of the 60mcg arm as opposed to 7% in the placebo group. Other adverse events reported in order of incidence for 60mcg and greater than with placebo were oral paresthesia or oral hypoesthesia (6% vs 4% placebo), dry mouth (5% vs 3% for placebo) and dizziness (3% vs 1% for placebo). Cardiovascular-related adverse events in the 60mcg group entailed 1 report of hypotension (0 in placebo), 1 of orthostatic hypotension (0 in placebo), and no reports of bradycardia or other cardiovascular adverse events in either group.

At-Home Agitation Market Insights: There are approximately 39 million annual episodes of agitation associated with bipolar disorders or schizophrenia in adults that occur in the U.S. Of these, an estimated 23 million (~60%) episodes occur outside of a medical institution. i Patients report feeling out of control and helpless when agitation episodes occur at home. ii. Episodes may occur three times a month on average, with the majority of them escalating to moderate or severe. iii. Physicians underdiagnose and undertreat these episodes in a community setting, with only a third of patients receiving prescription drugs, which are off-label and often suboptimal, for their agitation symptoms. iv. In a market survey, patients indicated they would take BXCL 501 for 80% of their agitation episodes. 90% of those patients indicated they would take BXC 501 when they feel an episode coming on or when an episode begins.

The Company plans to proceed with SERENITY III Part 2 using an adaptive trial design with 60mcg or greater dose, such as 80mcg, which has demonstrated statistical significance in the Company’s prior Phase 1b trial. The design may include potential repeat dosing as required to address the entire agitation spectrum for patients at home.