BioXcel Therapeutics Announces First Patient Dosed in TRANQUILITY II Phase 3 Trial for Acute Treatment of Agitation in Patients With Alzheimer’s Disease

BioXcel Therapeutics, Inc. recently announced the first patient has been dosed in the Phase 3 TRANQUILITY II study of 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 pivotal Phase 3 TRANQUILITY program includes two studies, TRANQUILITY II and TRANQUILITY III, which 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.

“There are an estimated 100 million agitation episodes annually in the US associated with Alzheimer’s disease, which have a devastating impact on patients and their caregivers,” said Robert Risinger, MD, Chief Medical Officer of BioXcel Therapeutics. “We believe the recent FDA approval of BXCL501 for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults has laid a strong foundation for pursuing this Alzheimer’s-related agitation program to potentially address this debilitating symptom for patients. Importantly, we are also expanding TRANQUILITY II to more than 10 clinical trial sites in the US and with no current FDA-approved treatments for agitation associated with this disease, we are making strong and swift efforts to potentially bring BXCL501 and its proven ability to address agitation to this large market.”

The company’s decision to continue the evaluation of both the 40- and 60-mcg dosing regimens in the TRANQUILITY II and III pivotal trials is further supported by results from a recent 46 patient, multicenter, placebo-controlled study evaluating the efficacy, safety and tolerability of BXCL501 40 mcg dose in patients with agitation associated with dementia. Previously, BXCL501 was granted Breakthrough Therapy designation from the US FDA for the acute treatment of agitation associated with dementia. BXCL501 demonstrated statistically significant reductions in agitation measures with both the 30- and 60-mcg doses as measured by multiple scales with no severe or serious adverse events.

Initiated in December of 2021, TRANQUILITY II and III are pivotal Phase 3 trials evaluating BXCL501 for the acute treatment of agitation in patients with Alzheimer’s disease. The trials expand the evaluation of patients who experience agitation across diverse medical settings and across the range of dementia severity. TRANQUILITY II and III are designed to maximize the opportunity of BXCL501 for the treatment of the full spectrum of agitation associated with AD. Each trial will enroll approximately 150 dementia patients 65 years and older who will self-administer 40 mcg or 60 mcg of BXCL501 or placebo whenever agitation episodes occur over a 3-month period. TRANQUILITY II will assess patients in assisted living or residential facilities requiring minimal assistance with activities of daily living. TRANQUILITY III will assess patients residing in nursing homes with moderate-to-severe dementia and require moderate or greater assistance with activities of daily living. The studies will 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 is change in PEC score from baseline measured at two hours after the initial dose and subsequent doses.

Alzheimer’s disease is the most prevalent type of dementia in the US. 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 US every year. There are no approved therapeutic options for the acute treatment of agitation related to dementia, including Alzheimer’s disease.

BioXcel Therapeutics, Inc. is a commercial-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. The company’s commercial product, IGALMI (developed as BXCL501) is a proprietary, sublingual film formulation of dexmedetomidine approved by the FDA for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. BXCL501 is also being evaluated for the acute treatment of agitation associated with Alzheimer’s disease, and as an adjunctive treatment for major depressive disorder. The company is also developing BXCL502 as a potential therapy for chronic agitation in dementia and, under its subsidiary OnkosXcel, BXCL701, an investigational, orally administered, systemic innate immunity activator 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.