BioXcel Therapeutics Announces Positive Phase 2 Topline Results from Columbia University-Led Study of BXCL501 for Treatment of Opioid Withdrawal

BXCL501 demonstrated clinical benefits and favorable tolerability profile for treatment of opioid withdrawal symptoms

Results from this NIDA-funded study support potential future development of BXCL501 in opioid withdrawal

Opioid use disorder is a global health crisis, affecting approximately 5.9 million adults in the U.S.

NEW HAVEN, Conn., March 05, 2026 (GLOBE NEWSWIRE) -- BioXcel Therapeutics, Inc. (Nasdaq: BTAI), a biopharmaceutical company built on artificial intelligence (“AI”) to develop transformative medicines in neuroscience, today announced positive topline results from a Phase 2 investigator-sponsored trial (IST) evaluating BXCL501 for the treatment of opioid withdrawal symptoms in adults with opioid use disorder (OUD) undergoing a methadone taper.

The study suggested that BXCL501 may be as effective as or superior to lofexidine (Lucemyra

) for reducing the symptoms of opioid withdrawal during methadone taper, while having a more convenient dosing regimen and demonstrating a favorable tolerability profile. In this study, BXCL501 had similar or lower overall rates of cardiovascular (CV) effects than lofexidine. Specifically, the most common CV adverse event for Lucemyra, orthostatic hypotension, was significantly lower for the 180 µg twice daily (BID) BXCL501 dose group (18% vs 50% lofexidine, p<0.05) and remained lower in the highest 240 µg BID BXCL501 dose group (37%) over the seven-day dosing period. There were no reports of sedation or somnolence in the BXCL501 treatment arms (5% reported sedation in the lofexidine arm). These results support potential future development of BXCL501 in opioid withdrawal.

These findings build on the earlier Company-sponsored Phase 1b/2 study, RELEASE,

which established the tolerability profile of selected BXCL501 doses in opioid-dependent patients and extend those results into a clinically distinct setting that included a methadone taper and an active comparator.

The results are consistent with the mechanism of action of BXCL501 (alpha 2-adrenergic receptor agonism), as locus coeruleus drives various opioid withdrawal symptoms.

These results strengthen the growing body of evidence supporting BXCL501 across multiple potential indications, reinforcing its potential as a “pipeline within a product.” These findings build on positive results from Phase 3 pivotal studies evaluating BXCL501 for the treatment of acute agitation associated with bipolar disorder and schizophrenia, as well as Alzheimer’s disease.

For this National Institute on Drug Abuse (NIDA)-funded study, BioXcel Therapeutics supplied BXCL501. This study was planned as a 4-arm trial: BXCL501 180 µg BID or 240 µg BID, placebo, and lofexidine 0.54 mg QID as a positive control. It enrolled participants who were predominantly exposed to fentanyl and included a high proportion of participants exposed to fentanyl adulterated or associated with xylazine (FAAX), which has been designated as an emerging threat by the White House Office of National Drug Control Policy.

The trial was completed after 80 patients were enrolled.

Key takeaways from the study include:

• BXCL501 240 µg BID reduced opioid withdrawal symptoms compared to placebo during a seven-day methadone taper, as measured by the Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop).
  
  • After receiving BXCL501 240 µg, patients experienced a greater than 30% reduction in SOWS-Gossop scores, with peak symptom improvement observed on days 3 and 4.
    
  • The reduction in withdrawal symptoms with BXCL501 numerically exceeded that observed with lofexidine 0.54 mg administered four times daily.
    
• BXCL501 demonstrated a favorable tolerability profile, with rates of key adverse events (including dizziness, orthostatic hypotension, bradycardia and insomnia) comparable to or lower than those reported for lofexidine in the Lucemyra
  ®
  (lofexidine) FDA label.

“As we continue to face a worldwide crisis encompassing a large patient population suffering from opioid use disorder, these results showcase an encouraging therapeutic milestone demonstrating the significant potential of BXCL501 as a therapy for meaningfully reducing opioid withdrawal symptoms,” said Dr. Sandra Comer, Principal Investigator of the study and Professor of Neurobiology in the Department of Psychiatry at Columbia University. “Opioid withdrawal remains a significant burden on the healthcare system and patients, and despite available therapies, there is still a substantial unmet need for safe and more effective treatment options that can help patients successfully transition to other medications such as buprenorphine or naltrexone for long-term benefits.” 

Notably, OUD remains a critical global health crisis, with an estimated 36 to 61 million people worldwide living with opioid dependence.

Approximately 85% of chronic opioid users experience at least one withdrawal episode every six months, suggesting that 30 to 50 million individuals globally may require withdrawal management each year. In the United States alone, approximately 5.9 million people have diagnosed OUD, and about 8.9 million report annual opioid misuse. Despite this substantial need, only about 25% of individuals with a substance use disorder receive specialized treatment, highlighting a significant treatment gap. Currently approved options for opioid withdrawal management are limited, and tolerability challenges may affect adherence, underscoring the potential importance of BXCL501’s differentiated profile as a non-opioid, orally dissolving thin film formulation of dexmedetomidine administered twice daily. Another potential advantage of BXCL501 is that it may be particularly well-suited for treating withdrawal from opioids adulterated with xylazine.

About BioXcel Therapeutics, Inc.

BioXcel Therapeutics, Inc. (Nasdaq: BTAI) is a biopharmaceutical company built on artificial intelligence (“AI”) to develop transformative medicines in neuroscience. Its wholly owned subsidiary, OnkosXcel Therapeutics, is focused on the development of medicines in 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 indications. For more information, please visit .

About BXCL501

Outside of its approved indication by the U.S. Food and Drug Administration as IGALMI

 (dexmedetomidine) sublingual film, BXCL501 is an investigational proprietary, orally dissolving film formulation of dexmedetomidine, a selective alpha-2 adrenergic receptor agonist. BXCL501 is under investigation by BioXcel Therapeutics for the acute treatment of agitation associated with Alzheimer’s dementia and for the acute treatment of agitation associated with bipolar I or II disorder or schizophrenia in the at-home setting. The safety and efficacy of BXCL501 for these investigational uses have not been established. BXCL501 has been granted Breakthrough Therapy designation by the FDA 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.

Forward-Looking Statements

Contact Information:

Corporate/Investors
Russo Partners
Nic Johnson
1.303.482.6405

Media
Russo Partners
David Schull
1.858.717.2310

Source: BioXcel Therapeutics, Inc.

References

1. Jones et al., Am J Drug Alcohol Abuse. 2023 49(1):109–122
2. Ivanov and Aston-Jones, Journal of Neurophysiology 2001 85:6, 2388-2397