Tonix Pharmaceuticals Holding Corp. a biopharmaceutical company, announced that it has completed enrollment of its potentially final, confirmatory Phase 3 RESILIENT trial of TNX-102 SL (cyclobenzaprine HCL sublingual tablets) 5.6 mg in fibromyalgia and expects topline data next quarter. A total of 457 participants were randomized. TNX-102 SL is in development as a non-opioid, centrally acting analgesic, to be taken daily at bedtime for the management of fibromyalgia. If successful, we believe this will be the final, well-controlled efficacy trial required for submission of a New Drug Application (NDA) for approval by the U.S. Food and Drug Administration (FDA).
“The completion of enrollment in our Phase 3 RESILIENT trial is a significant milestone for both Tonix and the fibromyalgia community,” said Seth Lederman, M.D., Chief Executive Officer of Tonix. “Currently-approved treatments have not fully met the needs of fibromyalgia patients and there has not been a new FDA-approved therapy for the condition since 2009. TNX-102 SL has the potential to be a new non-addictive, non-opioid bedtime medication with broad spectrum symptom coverage and which can be used on a chronic basis for the management of fibromyalgia. With all other clinical, nonclinical and CMC requirements for an NDA submission achieved, we are looking forward to the upcoming data readout and an expeditious filing of an NDA.”
In December 2020, Tonix reported positive results from the first Phase 3 study (RELIEF) of TNX-102 SL 5.6 mg for the management of fibromyalgia. TNX-102 SL met its pre-specified primary endpoint in the Phase 3 RELIEF trial, significantly reducing daily pain compared to placebo (p=0.01) in participants with fibromyalgia. Also, when the primary endpoint was analyzed as a ≥30% pain responder analysis, there was a higher rate of responders to TNX-102 SL (47%) than to placebo (35%; p=0.006). TNX-102 SL at 5.6 mg also showed activity in key secondary endpoints demonstrating improvements in sleep quality, mitigation of fatigue, and fibromyalgia-specific global symptomatic and functional recovery. TNX-102 SL was generally safe and well tolerated in patients with fibromyalgia, with overall adverse event profile comparable to prior fibromyalgia studies. The most common treatment-emergent adverse events were oral hypoesthesia, oral paresthesia, and product taste abnormal.
About the Phase 3 RESILIENT Study
The RESILIENT study is a double-blind, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) in the management of fibromyalgia. The two-arm trial randomized 457 participants in the U.S. The first two weeks of treatment consist of a run-in period in which participants start on TNX-102 SL 2.8 mg (1 tablet) or placebo. Thereafter, all participants increase their dose to TNX-102 SL 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 (TNX-102 SL 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.
About Fibromyalgia
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 6-12 million adults in the U.S., approximately 90% 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.
About TNX-102 SL
TNX-102 SL is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride which provides rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine, due to bypass of first-pass hepatic metabolism. As a multifunctional agent with potent binding and antagonist activities at the 5-HT2A-serotonergic, α1-adrenergic, H1-histaminergic, and M1-muscarinic receptors, TNX-102 SL is in development as a daily bedtime treatment for fibromyalgia, Long COVID (formally known as post-acute sequelae of COVID-19 [PASC]), alcohol use disorder and agitation in Alzheimer’s disease. The United States Patent and Trademark Office (USPTO) issued United States Patent No. 9636408 in May 2017, Patent No. 9956188 in May 2018, Patent No. 10117936 in November 2018, Patent No. 10,357,465 in July 2019, and Patent No. 10736859 in August 2020. The Protectic™ protective eutectic and Angstro-Technology™ formulation claimed in the patent are important elements of Tonix’s proprietary TNX-102 SL composition. These patents are expected to provide TNX-102 SL, upon NDA approval, with U.S. market exclusivity until 2034/2035.
Tonix Pharmaceuticals Holding Corp.
Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment in a potentially registration-enabling study, with topline data expected in the fourth quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 study has been completed, and topline results are expected in the third quarter of 2023.