Tonix Pharmaceuticals has announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for TNX-102 SL (cyclobenzaprine HCl sublingual tablets) 5.6 mg, a non-opioid, centrally-acting analgesic, as a potential treatment for fibromyalgia. The submission, announced on October 16, 2024, is based on positive data from two Phase 3 clinical trials demonstrating statistically significant reductions in chronic, widespread pain associated with fibromyalgia. If approved, TNX-102 SL could be the first new drug for fibromyalgia in over 15 years and the first of a new tricyclic class of medicines for this condition.
Clinical Trial Data
The NDA is supported by data from two 14-week, double-blind, randomized, placebo-controlled Phase 3 clinical trials. The RELIEF trial, completed in December 2020, met its primary endpoint, showing a significant reduction in daily pain compared to placebo (p=0.010). The confirmatory RESILIENT study, completed in December 2023, also met its primary endpoint, demonstrating a significant reduction in daily pain compared to placebo (p=0.00005). In both trials, TNX-102 SL was generally well-tolerated, with a comparable adverse event profile to prior studies and no new safety signals observed. The most common treatment-emergent adverse event was tongue or mouth numbness at the administration site, which was temporally related to dosing, self-limited, never rated as severe, and rarely led to study discontinuation.
Mechanism of Action and Formulation
TNX-102 SL is designed as a bedtime treatment to be taken daily on a chronic basis. Tonix believes that it relieves fibromyalgia pain by targeting the non-restorative sleep that is characteristic of fibromyalgia. The tablet is based on a proprietary eutectic formulation of cyclobenzaprine HCl and mannitol, providing a stable product that dissolves rapidly and delivers cyclobenzaprine efficiently into the bloodstream via the transmucosal route. Cyclobenzaprine interacts as an antagonist at four different receptors in the brain: serotonergic-5-HT2A, adrenergic-α1, histaminergic-H1, and muscarinic-M1-cholinergic receptors.
Unmet Need in Fibromyalgia
Fibromyalgia affects more than 10 million adults in the U.S., the majority of whom are women. Symptoms include chronic widespread pain, non-restorative sleep, fatigue, and cognitive dysfunction. Despite the availability of three FDA-approved medications, representing two different classes of medicines (gabapentinoids and SNRIs), a significant unmet need remains for new treatment options. Current treatments often have limited efficacy and are associated with side effects that can impact patient compliance.
Regulatory Pathway and Market Exclusivity
TNX-102 SL has been granted Fast Track designation by the FDA, which is designed to expedite the review of important new drugs to treat serious conditions and fill an unmet medical need. The FDA typically has a 60-day filing review period to determine whether the submitted NDA is complete and accepted for review. If the NDA is accepted, Tonix expects a 2025 date for an FDA decision on approval, based on the Prescription Drug User Fee Act (PDUFA). Patents based on TNX-102 SL’s eutectic composition and its properties have been issued in the U.S., E.U., Japan, China, and other jurisdictions, providing market protection into 2034.
Expert Commentary
"With the submission of this NDA, Tonix has achieved a critical milestone in potentially bringing a new first-line treatment option to the large and dissatisfied fibromyalgia population that has not had a new pharmacotherapy in over 15 years," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals, added, "If approved by FDA, TNX-102 SL would be the first of a new tricyclic class of medicines for treating fibromyalgia."
