By David Adam

Pictured: Person holding a cell phone in front of computer with stock data/iStock

The release of positive topline results Thursday from the Phase III trial of BioXcel Therapeutics’ Alzheimer’s-related agitation treatment was overshadowed by disclosures to the SEC about fabricated email correspondences pertaining to the study's safety data.
In a Thursday SEC filing, BioXcel said that a trial site’s principal investigator—who enrolled 40% of the study participants at that site—was found to have fabricated email correspondences related to the timing of the filing for a serious adverse event (SAE) with the company’s vendor responsible for the monitoring of drug safety. The adverse event occurred in a subject in the placebo arm, the company said.
In May 2023, it “came to the company’s attention that this same principal investigator in the TRANQUILITY II clinical trial may have fabricated email correspondence purporting to demonstrate that the investigator timely submitted to the company’s pharmacovigilance safety vendor a report of an SAE from a different subject than the one cited in the FDA Form 483, and purporting to show that the vendor had confirmed receipt," BioXcel stated in the SEC filing.
The problem was initially observed by the FDA after an inspection of the site in December, after which BioXcel started an investigation, according to the SEC filing. The company now plans to further investigate data integrity and protocol adherence.
BioXcel told BioSpace in an email that the company’s internal investigation is ongoing and that it is initiating an independent audit “as quickly as we are able.”
The company spokesperson said the “instance of a principal investigator’s fabrication of documentation pertains only to the correspondence between the principal investigator and the company’s pharmacovigilance vendor, and there is no allegation that the principal investigator fabricated or falsified any underlying data, including any information regarding the SAE itself.”
BioXcel would not speculate at this point on the impact to the TRANQUILITY II trial.
The drug, named BXCL501, is intended to treat patients with agitation related to Alzheimer’s disease. The trial results showed that the 60-mcg dose of the drug met the primary goal, showing a statistically significant reduction in acute agitation after two hours, compared with 5.4 hours for patients who were given a placebo.
Most patients (76%) responded to the 60-mcg dose and were determined to be “very much” or “much improved” compared to 50% on placebo. The primary endpoint was not met for a lower 40-mcg dose of the drug, with a 5.7-point reduction from baseline in the Positive and Negative Syndrome Scale-Excitatory Component (PEC) total score.
BioXcel said it will apply to expand the use of the drug in the second half of 2023. It is already FDA-approved to treat agitation associated with schizophrenia or bipolar I or II disorder in adults.
“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,” CEO Vimal Mehta said in a statement.
Investors were less convinced Thursday as BioXcel’s stock was down more than 60% in afternoon trading.