Tonix Pharmaceuticals Holding Corp., a clinical-stage biopharmaceutical company, announced on Monday that, TNX-102 SL (cyclobenzaprine HCl sublingual tablets) did not achieve statistical significance on the primary endpoint of reducing fibromyalgia (FM) in the Phase 3 RALLY study.
Fibromyalgia is a chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system. Symptoms of fibromyalgia include chronic widespread pain, nonrestorative sleep, fatigue, and morning stiffness. Other associated symptoms include cognitive dysfunction and mood disturbances, including anxiety and depression. The cause of fibromyalgia is not known, but it can be effectively treated and managed.
Based on previously reported pre-specified interim analysis results, TNX-102 SL did not reach statistical significance for the primary endpoint of fibromyalgia reduction(FM) daily pain at Week 14 compared to placebo (p=0.115) in the Phase 3 RALLY study.
RALLY was a 14-week randomized, double-blind, placebo-controlled trial of TNX-102 SL 5.6 mg, in which 514 participants with FM were randomized in a 1:1 ratio across 36 U.S. sites. All participants received TNX-102 SL 2.8 mg or placebo for the first two weeks, which was increased to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for the remaining 12 weeks.
Tonix reported interim analysis results of RALLY in July 2021 at which time the Independent Data Monitoring Committee recommended stopping the study as it was unlikely to succeed on the primary endpoint for the planned full sample. The Company therefore stopped enrollment of new participants while continuing those enrolled at that time to completion.
In December 2020, Tonix reported positive results from the Phase 3 RELIEF study of TNX-102 SL 5.6 mg for the management of FM (primary endpoint, p=0.010).
Dr. Gregory Sullivan, M.D., Chief Medical Officer of Tonix said:
The positive outcome of the earlier RELIEF study stands in contrast to the missed primary endpoint in RALLY. We believe the difference between these study results may be driven in large part by a 79% increase in adverse event-related participant discontinuations in the drug treatment group in RALLY as compared to RELIEF. Similarly, a 77% increase of adverse event-related participant discontinuations was observed in the placebo group in RALLY as compared to RELIEF.
The missing data for the primary and secondary endpoints were imputed by a method called ‘multiple imputation’ (MI), and discontinuations due to adverse events can negatively impact the statistical outcome when using this approach. Since 2010, The U.S. Food and Drug Administration (FDA) has generally required MI be used to account for missing data in efficacy analyses.
Dr. Seth Lederman, M.D., Chief Executive Officer of Tonix said:
Tonix remains dedicated to improving the lives of the millions suffering from fibromyalgia. FM is a complex syndrome, and while TNX-102 SL at 5.6 mg missed the primary endpoint in RALLY, it continued to show strong activity on sleep disturbance (p=0.004) and on the Patient Global Impression of Change (PGIC; p=0.038), which is a patient-reported assessment of overall improvement during the trial. These findings and our general understanding of TNX-102 SL tolerability encourage us to move forward with our plans to initiate our new F307 RESILIENT Phase 3 study for fibromyalgia in the first half of 2022.