Positive topline results from TRANQUILITY II, phase III trial of BXCL 501 for acute treatment of Alzheimer’s disease-related agitation

The Phase III trial met its primary efficacy endpoint with the 60 mcg dose; a statistically significant and clinically meaningful 7.5 point reduction from baseline in Positive and Negative Syndrome Scale-Excitatory Component (PEC) total score was observed at 2 hours versus 5.4 with placebo (p=0.0112). The 60 mcg dose also met the first key secondary endpoint of reducing agitation symptoms at 1 hour during the first episode of agitation (p=0.0185) but did not meet the other key secondary endpoint of change from baseline in PEC score at 30 minutes. Efficacy for this dose was supported by a number of secondary measures, including CGI-I and ACES. Most patients (76%) responded to the first 60 mcg dose and were determined to be “Very Much” or “Much Improved” (CGI-I of 1 or 2) compared to 50% with placebo. The primary endpoint was not met for the 40 mcg dose, with a 5.7 point reduction from baseline in PEC score.

BXCL 501 continued to show a PEC reduction over repeated dosing. A total of 443 episodes were dosed over the 12-week trial period, including 294 episodes occurring after the first treatment across all dose groups. Dosing with 60 mcg showed a reduction in PEC total score from pre-dose versus placebo at 1 hour (p=0.011) and 2 hours (p=0.0044) for all episodes of agitation.

“We believe these results represent a significant milestone for BioXcel Therapeutics and a potential important step forward in our goal to helping those impacted by Alzheimer’s disease,” said Vimal Mehta, CEO of BioXcel Therapeutics. “Today, there are approximately 100 million Alzheimer’s-related agitation episodes in the U.S. annually, and there are no episodic treatment options for these patients. We believe that our data from TRANQUILITY II show that BXCL 501 has the potential to treat acute episodes of agitation in patients with mild to moderate Alzheimer’s disease, if approved. This is particularly critical as the prevalence of this disease is expected to nearly double over the next 15 to 20 years. We are excited at the prospect of continuing to expand BXCL 501’s market potential.”

BXCL 501 was well tolerated, with a side effect profile substantially consistent with prior trials of BXCL 501 and the current label for Igalmi. The 60 mcg dose had previously been evaluated in different patient populations and in healthy volunteers. Data from TRANQUILITY II add to this safety database and show that the majority of safety events occurring within 24 hours of dosing in this population were mild or moderate in severity and consistent with the current Igalmi label. In addition, dosing for subsequent episodes did not result in a meaningful increase in the number of adverse events and no treatment-related serious adverse events were observed over the 12-week study period.

For all 443 episodes over the 12-week period, there were no syncope or falls related to trial drug. All falls except one with placebo were outside the 24-hour treatment window (5 falls in the 40 mcg arm, 7 falls in the 60 mcg arm, and 5 falls in the placebo arm).

“I believe that the results from the TRANQUILITY II trial are an exciting development for potentially addressing Alzheimer’s disease-related agitation,” said George Grossberg, M.D., Professor and Director Division of Geriatric Psychiatry in the Department of Psychiatry & Behavioral Neuroscience at St. Louis University School of Medicine. “In this trial, BXCL501 showed a desirable onset of action and a meaningful reduction in agitation at 2 hours with the 60 mcg dose, and was well tolerated in this patient population. I believe it has potential to be a new treatment option for a condition that not only impacts patients but also caregivers and families.”