An interim analysis of the phase III Recovery study of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) for treating post-traumatic stress disorder (PTSD) compelled Tonix Pharmaceuticals Holding Corp. to halt enrollment in the clinical trial.
Based on an analysis of half of the enrolled patients, the independent data monitoring committee recommended stopping the trial for futility, saying the drug, also known as Tonmya, is unlikely to demonstrate a statistically significant improvement in the primary endpoint of overall change from baseline in the severity of PTSD symptoms. Tonix intends to study those who are enrolled until the Recovery trial’s end and report top-line data in the second quarter of 2020.
Tonix will shift money allocated for the PTSD program into its fibromyalgia study of Tonmya that’s in a phase III, which is currently enrolling. Interim results should come in the second half of 2020.
In November, following a meeting with the FDA, analysis of the primary endpoint for the Recovery study, the mean change from baseline in the Clinician-Administered PTSD Scale for DSM-5, was changed from week four to week 12. That set the stage for the interim analysis, allowing for a potential sample size adjustment or stopping for futility after 125 of the targeted 250 patients have completed or discontinued the 12-week treatment.
Tonix’s stock (NASDAQ:TNXP) struggled mightily Thursday, dropping 83 cents, or 48.8%, to 87 cents.
Tonmya’s past has been turbulent. In July 2018, the phase III Honor study, using Tonmya and designed to study bedtime relief from symptoms of military-related PTSD, failed to adequately separate from placebo in an interim analysis at 12 weeks. The FDA, in March 2019, notified Tonix that Tonmya’s breakthrough therapy designation, granted in late 2016, was rescinded because the study’s interim analysis data did not support the designation’s continuation.
There are 380 ongoing clinical trials in PTSD, according to Cortellis. H. Lundbeck A/S and Otsuka Pharmaceutical Co. Ltd. showed positive data in November 2018 for their phase II study designed to assess the efficacy, safety and tolerability of flexible doses of brexpiprazole as a monotherapy, flexible doses of sertraline as a monotherapy or combination therapy with both brexpiprazole and sertraline in adults with PTSD. As measured by the Clinician-Administered PTSD Scale for DSM-5 total score change from baseline compared to placebo, when brexpiprazole and sertraline were given in combination, the “p” value was <0.01. However, the treatment effects of brexpiprazole alone demonstrated no clinically meaningful differences in comparison to placebo on the primary endpoint (p>0.35). The treatment effects of sertraline alone also did not demonstrate clinically meaningful differences in comparison to placebo on the primary endpoint (p>0.60). Lundbeck and Otsuka now have a phase III underway.
Addex Therapeutics SA, of Geneva, said in July it would lead a consortium to develop small-molecule negative allosteric modulators (NAMs) targeting the metabotropic glutamate receptor 7 (mGlu7) to reduce fear memory in PTSD. The project, DiSARM FEAR, was awarded a Eurostars grant of approximately €4.9 million (US$5.4 million) to cover research activities performed by the participants, which also include Naason Science, of South Korea, Germany's Endotherm GmbH, Nucro Technics Inc., of Canada, and Radboud University, with the goal of generating mGlu7 NAMs that can advance to IND-enabling studies within three years.
Adelaide, Australia-based Bionomics Inc. reported another trial failure with its lead compound, BNC-210, in elderly patients with agitation, but clings to hopes that the compound will show a clinical benefit for PTSD. After reporting a trial failure in October 2018 for BNC-210, a negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor, in a phase II PTSD trial, Bionomics conducted a drug exposure-response analysis that saw a positive effect once adequate blood levels were reached, and the company decided to revive the compound for PTSD. In November, the FDA granted it fast track designation.
In January, Aptinyx Inc., of Evanston, Ill., said it closed its public offering of about 11.7 million shares, including the exercise of the full underwriters’ overallotment option, priced at $3 per share for gross proceeds of about $35.1 million. Proceeds will be used to advance preclinical and clinical development of NMDA receptor modulators, including NYX-783 for PTSD.