Investigational Rapid-Acting PTSD Medication Awarded FDA Breakthrough Therapy Status: Transcend Therapeutics Update

The FDA on July 10 granted Breakthrough Therapy designation to TSND-201 (methylone), an investigational rapid-acting neuroplastogen developed by Transcend Therapeutics for the treatment of post-traumatic stress disorder (PTSD). 1

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The designation is based on positive results from the IMPACT-1 study, a phase 2 trial evaluating the safety and efficacy of TSND-201 in 65 patients with severe PTSD. Participants received 4 oral doses of TSND-201 or placebo over 4 weeks and were followed for 64 days.1

The randomized, double-blind, placebo-controlled IMPACT-1 met its primary endpoint, demonstrating a statistically significant placebo-adjusted improvement in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score of -9.64 points on day 64 (TSND-201: -23.28; placebo: -13.64; P = .011).2 Rapid improvements were observed as early as day 10, according to the company, with a statistically significant placebo-adjusted CAPS-5 improvement of -8.00 points (TSND-201: -17.83; placebo: -9.83; P = .012), effects that were durable through the end of the study.2 Transcend also reported significant improvements across key secondary endpoints, including response (equal to or greater than 50% CAPS-5 improvement: 57.1% vs. 19.2%; P = .002), remission (CAPS-5 11 or greater: 32.1% vs. 11.5%; P = .036), and loss of PTSD diagnosis (60.7% vs. 30.8%; P = .014)2.

Tolerability was generally good, according to the statement. The most common adverse events (AEs) were mild and transient, including headache, decreased appetite, nausea, dizziness, and dry mouth. A single seizure, considered a serious AE, occurred in a patient with a seizure history and was deemed unrelated to the study drug. Transcend reported there were no hallucinations or discontinuations due to AEs.2

"This designation underscores the urgent need for new, more effective treatments for the 13 million Americans living with PTSD," Blake Mandell, co-founder and CEO of Transcend Therapeutics, said in the July 10 statement.1 Mandell noted that there are jut 2 FDA-approved medications today to treat the disorder and that there has been no new PTSD therapy approved in more than 20 years. The Breakthrough Therapy designation "enables us to work more closely with the FDA as we prepare to launch our Phase 3 program," he said.1

Findings from the phase 2 study suggest that the neuroplastogen may represent a significant clinical breakthrough, showing both clinically meaningful efficacy and rapid onset," according to Murray B. Stein, MD, MPH, distinguished professor of psychiatry and public health at the University of California San Diego and staff psychiatrist at the Veteran Affairs San Diego Healthcare System. "Rapid-acting, episodic treatments could be a paradigm shift in the treatment of PTSD, providing hope for the many patients who have struggled to find effective relief."2

PTSD affects an estimated 13 million adults in the US every year, with lifetime prevalence around 6% to 7%, according to Transcend. The condition is associated with significant psychiatric and physical comorbidity, functional impairment, and increased suicide risk. Current FDA-approved pharmacologic options, sertraline and paroxetine, are associated with delayed onset of action, frequent side effects, and limited overall efficacy. New treatments remain an urgent clinical need, the company stated.

References

1. Transcend Therapeutics receives breakthrough therapy designation for TSND-201 (methylone) for the treatment of PTSD. News release. Transcend Therapeutics. July 10, 2025. Accessed July 10, 2025. https://transcendtherapeutics.com/transcend-therapeutics-receives-breakthrough-therapy-designation-for-tsnd-201-methylone-for-the-treatment-of-ptsd/

2. Transcend Therapeutics announces primary endpoint met in IMPACT-1 Phase 2 study of TSND-201 in PTSD. News release. Transcend Therapeutics. March 31, 2025. Accessed July 10, 2025. https://transcendtherapeutics.com/impact-1-primary-endpoint-met/