Following the news that BioXcel Therapeutics announced positive top-line results from TRANQUILITY II (NCT05271552), a Phase III study of Igalmi (dexmedetomidine sublingual film) for the acute treatment of agitation episodes associated with Alzheimer’s disease (AD);

Philippa Salter, Senior Neurology Analyst at GlobalData, offers her view:

“Although the clinical trial met its primary endpoint for the high dose of the drug, the positive results have been overshadowed by several counts of bad clinical practice disclosed by the company, and therefore there are concerns surrounding the validity of some of the data from the trial.

“Igalmi was approved by the FDA for agitation associated with bipolar disorder and schizophrenia in April 2022. A label expansion into AD is a key strategy for BioXcel, as there is a much larger potential patient population in this indication, particularly with an aging global population, combined with a lack of treatments targeting agitation associated with AD. If an additional clinical trial was to be required by the FDA, it will put BioXcel on the back-foot in the market for treating agitation associated with AD, delaying Igalmi’s launch behind many potential competitors.

“There are several other products currently in Phase III development for AD-related agitation, including Avanir Pharmaceuticals’s deuterated form of dextromethorphan/quinidine AVP-786, Axsome Therapeutics’s NMDA-R antagonist Auvelity (bupropion + dextromethorphan), and Suven Life Sciences’s 5-hydroxytryptamine receptor 6 antagonist masupirdine. Additionally, Otsuka’s Rexulti (brexpiprazole) became the first drug to be approved by the FDA for agitation associated with AD, on May 10, 2023.

“Furthermore, even if the clinical trial data is deemed sufficient to allow a supplemental drug application and subsequent approval, there could still be negative opinion surrounding BioXcel and Igalmi, resulting in preferential use of other products by physicians and patients, damaging potential sales for the drug. BioXcel is making good strides in addressing the issue but will need to provide ample data to the AD community to ensure future trust.”