Tonix Pharmaceuticals Holding Corp. announced the presentation of additional efficacy data from RESILIENT, the second positive Phase 3 study evaluating Tonmya (also known as TNX-102 SL, cyclobenzaprine HCl sublingual tablets) for the management of fibromyalgia, at the 6th International Congress on Controversies in Fibromyalgia in Brussels, Belgium, March 7-8, 2024. As previously announced, RESILIENT met its pre-specified primary endpoint, significantly reducing daily pain compared to placebo (p=0.00005) in participants with fibromyalgia.

RELIEF, the first Phase 3 trial of Tonnya 5.6 mg in fibromyalgia, was completed in December 2020. It also met its pre-specified primary endpoint of daily pain reduction compared to placebo (p=0.010). Tonix plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the second half of 2024 and has scheduled a pre-NDA meeting with FDA in the second quarter of 2024.

Tonmya was not associated with increases in systolic or diastolic blood pressure or body weight, nor were there any reported sexual side effects in the RESILIENT trial. In addition, when systematically investigated using the Changes in Sexual Functioning Questionnaire short form (CSFQ-14), women who received study drug had a higher CSFQ-14 total score relative to those who received placebo, which is consistent with improved sexual function. The RESILIENT study is a double-blind, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of Tonmya (cyclobenzaprine HCl sublingual tablets) in the management of fibromyalgia.

The two-arm trial randomized 457 participants in the U.S. across 33 sites. The first two weeks of treatment consist of a run-in period in which participants start on Tonmya 2.8 mg (1 tablet) or placebo. Thereafter, all participants increase their dose to Tonmya 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for the remaining 12 weeks.

The primary endpoint is the daily diary pain severity score change (Tonmya 5.6 mg vs. placebo) from baseline to Week 14 (using the weekly averages of the daily numerical rating scale scores), analyzed by mixed model repeated measures with multiple imputation. The results showed that Tonmya treatment resulted in an improvement in cognitive dysfunction or ?brain fog?

measured by the change in the FIQ-R memory item. The FIQ-R cognition item showed improvement in Tonmya treated patients vs placebo treated patients (LS mean (SE) difference of -0.8 (0.23); nominal p=0.001; effect size 0.31, no correction for multiple comparisons, mixed model repeated measures analysis). The Cohen?s d effect sizes (ESs) of the five continuous key secondary outcomes measures were: Fibromyalgia Impact Questionnaire-Revised (FIQ-R) ?

Symptoms domain ES = 0.44, FIQ-R-Function ES =0.30, PROMIS sleep disturbance ES =0.50, PROMIS Fatigue ES = 0.37 and Dairy Sleep quality rating ES = 0.32. The most common adverse events were local administration site reactions that were transient and self-limited. Fibromyalgia is a chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system.

Fibromyalgia afflicts an estimated 6 million to 12 million adults in the U.S., the majority of whom are women. 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.

Individuals suffering from fibromyalgia struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products. Tonmya is a centrally acting, non-opioid, non-addictive, bedtime medication.

The tablet is a patented sublingual formulation of cyclobenzaprine hydrochloride developed for the management of fibromyalgia. In December 2023, the company announced highly statistically significant and clinically meaningful topline results in RESILIENT, a second positive Phase 3 clinical trial of Tonmya for the management of fibromyalgia. In the study, Tonmya met its pre-specified primary endpoint, significantly reducing daily pain compared to placebo (p=0.00005) in participants with fibromyalgia.

Statistically significant and clinically meaningful results were also seen in all key secondary endpoints related to improving sleep quality, reducing fatigue and improving overall fibromyalgia symptoms and function. RELIEF, the first positive Phase 3 trial of Tonmya in fibromyalgia, was completed in December 2020. It met its pre-specified primary endpoint of daily pain reduction compared to placebo (p=0.010) and showed activity in key secondary endpoints.