1231: TNX-102 SL, Cyclobenzaprine HCl Sublingual Tablets, Demonstrates Pain Reduction and Favorable Tolerability in Patients with Fibromyalgia

Background/Purpose: FDA-approved treatments for fibromyalgia (FM) have historically been limited by intolerable side effects that often lead to poor adherence. TNX-102 SL, a sublingual formulation of cyclobenzaprine, is under evaluation by the FDA as a treatment for FM. TNX-102 SL treatment has shown statistically significant reduction in pain in two Phase 3 studies, including the RESILIENT study reported below. In these studies, TNX-102 SL was generally well tolerated. The tolerability of TNX-102 SL may provide an appealing alternative to existing therapies.

Methods: The RESILIENT study was a 14-week, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of TNX-102 SL in patients with FM. The pre-specified primary endpoint was the change from baseline to Week 14 in the weekly average of daily pain numeric rating scale (NRS) scores, analyzed using a mixed model for repeated measures with multiple imputation for missing data. Exploratory secondary endpoints included assessments of tolerability, such as changes in sexual function (measured by CSFQ-14) and weight gain. Safety evaluations included changes in blood pressure and the incidence of adverse events (AEs).

Results: TNX-102 SL demonstrated significant improvement in the primary pain endpoint compared to placebo (p < 0.0001) at Week 14. Females treated with TNX-102 SL had significantly greater improvements in desire/frequency (p = 0.010), orgasm/completion (p = 0.007), and total sexual function scores (p = 0.010). No significant differences were observed between TNX-102 SL and placebo in weight, systolic, or diastolic blood pressure at Week 14. The most commonly reported AEs were mild to moderate, self-limited events such as transient tongue or mouth numbness and bitter aftertaste, which rarely led to study discontinuation. Systemic AE rates, excluding COVID-19, remained below 4.0%.

Conclusion: TNX-102 SL significantly reduced pain and showed a favorable tolerability profile, including minimal impact on weight and blood pressure, along with its unique mechanism targeting sleep disturbances, supports its potential as a new treatment option for FM. The availability of a well-tolerated treatment may also encourage clinicians to make the diagnosis of fibromyalgia earlier, thereby improving patient outcomes through timely intervention.