BioXcel Therapeutics Initiates Pivotal Phase 3 Program of BXCL501 for Acute Treatment of Agitation in Patients With Alzheimer’s Disease

BioXcel Therapeutics, Inc. recently announced the initiation of its pivotal Phase 3 program for BXCL501, the company’s proprietary, orally dissolving thin film formulation of dexmedetomidine, for the acute treatment of agitation in patients with Alzheimer’s disease (AD). The program’s two studies, TRANQUILITY II and TRANQUILITY III, are designed to evaluate the safety and efficacy of BXCL501 in adults 65 years and older in assisted living or residential facilities and nursing homes.

“We received FDA breakthrough therapy designation for BXCL501 in March 2021 based on our Phase 1b/2 TRANQUILITY study. Following multiple meetings with the FDA, we are pleased to announce the initiation of our Phase 3 program,” said Vimal Mehta, PhD, CEO of BioXcel Therapeutics. “This marks an important advancement in potentially bringing this novel treatment to the more than 4 million patients, who experience agitation as one of AD’s most devastating symptoms. We are leading the development path for this innovative therapy and are confident in BXCL501’s potential to treat acute, as well as intermittent, forms of agitation.”

The program expands the evaluation of patients in diverse medical settings across the range of dementia severity. It is designed to maximize the opportunity of BXCL501 for the treatment of the full spectrum of agitation associated with AD.

Pivotal Phase 3 Program Summary

• The program will consist of two randomized, placebo-controlled, adaptive, parallel group pivotal trials, TRANQUILITY II and TRANQUILITY III.
• Each study will enroll 150 dementia patients 65 years and older. Patients will self-administer 40 mcg or 60 mcg of BXCL501 or placebo whenever agitation episodes occur over a three-month period.
• TRANQUILITY II will enroll patients in assisted living or residential facilities requiring minimal assistance with activities of daily living. TRANQUILITY III will enroll patients in nursing homes with moderate to severe dementia requiring moderate or greater assistance with activities of daily living.

• The studies are designed to assess agitation as measured by the changes from baseline in the Positive and Negative Syndrome Scale-Excitatory Component (PEC) and Pittsburgh Agitation Scale (PAS) total scores. The primary efficacy endpoint for both studies will be change in PEC score from baseline measured at two hours after the initial dose and subsequent doses.
• Patients who complete TRANQUILITY II or TRANQUILITY III will be eligible to enroll in an open label, 52-week safety study designed to measure the safety and efficacy of BXCL501 in continued use.

BXCL501 is an investigational, proprietary, orally dissolving thin film formulation of dexmedetomidine, a selective alpha-2a receptor agonist for the treatment of agitation associated with neuropsychiatric disorders. BioXcel Therapeutics believes that BXCL501 potentially targets a causal agitation mechanism, and the Company has observed anti-agitation results in multiple clinical studies across several neuropsychiatric disorders, including schizophrenia-related agitation (SERENITY I), bipolar disorder-related agitation (SERENITY II) and dementia-related agitation (TRANQUILITY). BXCL501 has been granted Breakthrough Therapy designation for the acute treatment of agitation associated with dementia and Fast Track designation for the acute treatment of agitation associated with schizophrenia, bipolar disorders and dementia. The safety and efficacy of BXCL501 has not been established.

Alzheimer’s disease is the most prevalent type of dementia in the United States. By 2040, approximately 12 million Americans aged 65 years and over are expected to be impacted by the condition, double the approximately 6 million Americans impacted in 2020. Of these patients, up to 70% experience agitation, with an estimated 100 million agitation episodes occurring in the United States every year. There are no approved therapeutic options for the acute treatment of agitation related to dementia, including Alzheimer’s disease.

The randomized, double-blind, placebo-controlled, ascending dose, adaptive Phase 1b/2 study was designed to evaluate the efficacy, pharmacokinetics, safety, and tolerability of BXCL501 in adults 65 years and older who exhibit acute agitation associated with all forms of dementia, including Alzheimer’s disease. Following the completion of each dose cohort, a safety and tolerability review was performed to determine the next tested dose. The study was designed to assess agitation as measured by the changes from baseline in PAS and PEC total scores, as well as by improvements from baseline in the Mod-CMAI total score.

The PEC total score is a validated endpoint for measuring acute agitation in schizophrenia and bipolar patients. This scale is used in clinical research to quantify the severity of a patient’s acute agitation. The PEC rating evaluates 5 elements associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement; each scored 1 (minimum) to 7 (maximum). The PEC total score is the sum of these 5 elements and thus ranges from 5 to 35.

PAS is a validated instrument used to monitor the severity of agitation associated with dementia. The PAS measures 4 behavior groups: aberrant vocalization, motor agitation, aggressiveness, and resisting to care. The groups are evaluated on a scale from 0 to 4, with 0 defined as no agitation present and 4 defined as the highest form of agitation. The PAS total score ranges from 0 to 16.

BioXcel Therapeutics, Inc. is a clinical-stage biopharmaceutical company utilizing artificial intelligence approaches to develop transformative medicines in neuroscience and immuno-oncology. The company’s drug re-innovation approach leverages existing approved drugs and/or clinically validated product candidates together with big data and proprietary machine learning algorithms to identify new therapeutic indices. BioXcel Therapeutics’ two most advanced clinical development programs are BXCL501, an investigational, proprietary, orally dissolving thin film formulation of dexmedetomidine for the treatment of agitation associated with psychiatric and neurological disorders, and BXCL701, an investigational, orally administered, systemic innate immunity activator in development for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment naïve to checkpoint inhibitors. For more information, visit www.bioxceltherapeutics.com.