BioXcel Therapeutics (NASDAQ:BTAI) hosted a key opinion leader (KOL) virtual roundtable focused on acute agitation episodes in Alzheimer’s dementia, highlighting what participants described as a major unmet need for patients, caregivers, and clinicians. CEO Vimal Mehta opened the event by emphasizing that there are currently no FDA-approved treatments specifically for acute episodes of agitation in Alzheimer’s dementia and said the company remains focused on advancing BXCL501 for this setting.
Mehta referenced previously announced results from a Phase III pivotal study of BXCL501 for the acute treatment of agitation in Alzheimer’s dementia, stating that the product candidate was well-tolerated and met its primary efficacy endpoint.
Clinicians describe acute agitation as a distinct and common problem
Grossberg said diagnostic criteria developed by the International Psychogeriatric Association (IPA) largely emphasize persistent day-to-day agitation lasting at least two weeks, which he argued does not address intermittent acute episodes. He added that acute agitation can drive heavy healthcare resource utilization, including transfers from nursing homes and home settings to emergency rooms.
Sanford, who described her work in nursing home settings, said clinicians in acute situations often rely on “last resort” approaches with medications that are not ideal for older adults. She characterized the overall issue as “a very chronic problem with acute flares” that can strongly affect quality of life for patients and caregivers.
Porsteinsson described episodic (acute) agitation as occurring across care settings—long-term care, assisted living, and at home—and said it can arise even in individuals who do not have chronic agitation. He also noted that breakthrough episodes may occur even when a patient is being treated for persistent agitation. He cited potential triggers including confusion, being overwhelmed, pain, inability to communicate discomfort, and resistance around personal care needs.
Current approaches and the role of off-label medications
Panelists repeatedly returned to the lack of an FDA-approved treatment specifically designed for acute agitation episodes. Grossberg said clinicians frequently use off-label treatments in hospital settings, including antipsychotics such as quetiapine and olanzapine, which he said can sedate patients, increase fall risk, and make it harder to evaluate underlying causes of agitation.
Porsteinsson also noted that some sedating medications used in community settings may lead to hours of sedation and are cautioned against for overuse in older adults. He argued that a key need is a more predictable option with rapid onset that calms patients without producing heavy sleepiness.
Grossberg added that an additional consideration for some clinicians is that antipsychotics carry a boxed warning regarding increased mortality, which can make prescribers reluctant to use them in certain settings.
Discussion centers on BXCL501’s onset, delivery, and safety considerations
In the roundtable, BXCL501 was discussed as an oral thin-film formulation of dexmedetomidine administered on the oral mucosa for absorption. Porsteinsson said the delivery system can be workable even for patients with moderate to advanced dementia in skilled nursing facilities, though he cautioned there will not be a “100% success rate” in every situation.
Panelists discussed whether patients could self-administer medication during episodes. Grossberg said self-medication is generally unlikely in Alzheimer’s dementia and that caregivers and staff typically identify agitation and make treatment decisions. Porsteinsson noted that in some cases, patients experiencing distress may still accept help, and he contrasted the thin-film approach with scenarios where injections might be difficult or unsafe during intense agitation.
On timing, Porsteinsson said changes can be seen within about 30 minutes, with greater separation between drug and placebo at around 60 minutes, and he characterized the most intense “off the rocker” events as relatively rare compared with more common mid-level episodes where non-pharmacological approaches may not be sufficient.
In a discussion of safety considerations, Porsteinsson cited side effects he said were observed in the TRANQUILITY II study, including somnolence in the mild-to-moderate range and mild drops in blood pressure, while describing lethargy as rare. He also pointed to dexmedetomidine’s history of use in ICU settings in intravenous form. Grossberg said that established use in medically complex ICU patients provides comfort regarding its profile, albeit in a different formulation.
Panelists also discussed potential real-world use alongside chronic agitation therapy. Grossberg said he would not expect major issues using the oral film for breakthrough episodes in a patient treated with brexpiprazole for persistent agitation, while noting it had not been specifically studied to his knowledge.
Potential impact on caregivers and care settings
In closing remarks, Sanford said she sees a potential role for an as-needed option in helping caregivers keep patients at home longer and potentially delaying institutionalization. Porsteinsson emphasized the desire for a treatment with reliable absorption, defined onset, and a “reasonable” duration of effect for episodic events that interfere with activities such as personal care or travel.
Grossberg also described a separate scenario where a medication like BXCL501 could be useful: an older hospitalized patient with delirium and agitation, where clinicians need behavioral control without excessive sedation to allow evaluation of underlying causes. He noted such use could be off-label if the product is shown to be safe and well-tolerated.
Mehta closed the event by thanking participants and reiterating the company’s view that a significant gap remains in treating sudden episodic agitation events in Alzheimer’s dementia. He said advancing solutions tailored to acute episodes remains a priority for BioXcel Therapeutics.
About BioXcel Therapeutics (NASDAQ:BTAI)
BioXcel Therapeutics, Inc is a biopharmaceutical company leveraging an AI-driven drug development platform to identify and advance novel or repurposed therapies in neuroscience and immunology. The proprietary BioXcel AI engine analyzes preclinical and clinical data to reveal new therapeutic applications for existing small molecules and biologics, aiming to streamline development timelines and improve patient outcomes.
BioXcel’s commercial portfolio includes two FDA-approved therapies. IGALMI® (dexmedetomidine) is indicated for the acute treatment of agitation in schizophrenia or bipolar I disorder, offering a noninvasive, sublingual delivery option.
