Tonix Pharmaceuticals Holding Corp. a biopharmaceutical company, today announced the completion of the clinical phase of the Phase 2 proof-of-concept PREVAIL study of TNX-102 SL as a potential treatment for fibromyalgia-type Long COVID. Topline results for the PREVAIL study are expected in the third quarter of 2023.
“Approximately 40% of U.S. Long COVID patients have fibromyalgia-like multi-site pain symptoms based on our observational studies of Long COVID patients from the TriNetX claims database,”2,3 said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “In addition to multi-site pain, these individuals often suffer from one or more other symptoms typically associated with fibromyalgia such as fatigue, sleep disturbance, and brain fog. We have termed this subgroup, ‘Fibromyalgia-type Long COVID.’ Given our encouraging results with TNX-102 SL as a potential treatment for fibromyalgia4, we are testing TNX-102 SL as a bedtime medicine for the management of Fibromyalgia-type Long COVID. In completing this clinical milestone, marked by the last enrolled patient finishing their final visit, we can now begin to look forward to topline results from the 63-patient PREVAIL study later this quarter.”
Dr. Lederman continued, “TNX-102 SL improves sleep quality in fibromyalgia, and we believe this is the mechanism by which TNX-102 SL improves other symptoms, like multi-site pain.5 Recently, the U.S. National Institutes of Health (NIH) has identified improving sleep quality as a target for potential therapeutics for Long COVID6,7,8, consistent with the proposed mechanism of TNX-102 SL.
“Common symptoms of Long COVID, including multi-site pain, fatigue, unrefreshing sleep, and cognitive dysfunction, or ‘brain fog,’ are also hallmarks of conditions like fibromyalgia and chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME),”9 said Herbert Harris, M.D., Ph.D., Executive Vice President and Head of Translational Medicine of Tonix Pharmaceuticals. “Defining subgroups of Long COVID patients that overlap with fibromyalgia and CFS/ME is expected to facilitate the development of new treatments.4 It can be challenging to distinguish fibromyalgia and CFS/ME clinically, given the high level of symptom overlap between them. Each of these conditions is defined by a constellation of symptoms, and there is no widely recognized diagnostic laboratory test that distinguishes them.”
Dr. Harris continued, “The recent identification of Long COVID subgroups in the National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored RECOVER study10 was an important step. In their recent publication, cluster analysis of the symptom frequencies in the RECOVER study identified four subgroups of Long COVID patients. Cluster #4 represented approximately one-quarter of the population (28%) and reported the highest frequencies of pain (back pain (58%), joint pain (64%) or muscle pain (60%)), high frequencies of fatigue (94%) and ’Brain Fog,’ (94%) and a high level of impairment of Quality of Life. We believe Cluster #4 is a subgroup of Long COVID that shares many clinical features with fibromyalgia and may involve common disease mechanisms. We also believe that Cluster #3, representing another approximately 29% of the RECOVER cohort, includes many patients with fibromyalgia-type Long COVID because 100% of that group suffer from ‘Brain Fog’, 94% experience fatigue and approximately one-third
experience pain (back pain (32%), joint pain (36%) or muscle pain (34%)).”
Dr. Harris concluded, “With no FDA approved treatment for Long COVID, we understand the need to better understand long COVID and to develop treatments for subgroups of this unserved population of patients. Fibromyalgia has been recognized by the U.S. Food and Drug Administration (FDA) with three approved medicines. Consequently, measuring daily pain is a validated endpoint for FDA registrational studies in fibromyalgia. We believe that daily pain has the potential to be an endpoint for registrational studies in fibromyalgia-like long COVID.”
About the Phase 2 PREVAIL Study
The Phase 2 PREVAIL study is a 14-week double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of TNX-102 SL taken daily at bedtime in patients with multi-site pain associated with post-acute sequelae of SARS-CoV-2 infection (PASC). The trial is being conducted at approximately 30 sites in the U.S. The primary efficacy endpoint will be the change from baseline in the weekly average of daily self-reported worst pain intensity scores at the Week 14 endpoint. Key secondary efficacy endpoints include change from baseline in self-reported scores for sleep disturbance, fatigue, and cognitive function. Topline results are expected in the third quarter of 2023.
About Long COVID or Post-Acute Sequelae of COVID-19 (PASC)
Post-acute sequelae of COVID-19, or PASC is the formal name for a condition now widely known as Long COVID. Although most people recover from COVID-19 within weeks of the acute illness, a substantial portion develops a chronic syndrome called Long COVID.11 These individuals experience a constellation of disabling symptoms long past the time of recovery from acute COVID-19. Most Long COVID patients who have been studied appear to have cleared the SARS-CoV-2 infection from their systems. The symptoms of Long COVID can include fatigue, sleep disorders, multi-site pain, fevers, shortness of breath, cognitive impairment described as “brain fog” or memory disturbance, gastrointestinal symptoms, anxiety, and depression. According to the Centers for Disease Control and Prevention (CDC), 1 in 13 adults in the U.S. (7.5%) have Long COVID symptoms.1 Long COVID is typically associated with moderate or severe COVID-19, but can occur after mild COVID-19 or even after asymptomatic SARS-CoV-2 infection. More than 40% of adults in the United States reported having COVID-19 in the past, and nearly one in five of those (19%) are currently still having symptoms of Long COVID.1 Long COVID is a chronic disabling condition that is expected to result in a significant global health and economic burden.12-15
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.
About 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 Medicines, our commercial subsidiary markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories from whom the products were acquired on June 30, 2023. 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 development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in the fourth quarter of 2023.