Clinical Study of Fibromyalgia-Type Long COVID Agent Completed, Results to Come Soon

Seth Lederman, MD

According to an announcement from Tonix Pharmaceuticals, the company has completed the clinical phase of its phase 2 proof-of-concept PREVAIL study (NCT05472090) assessing its investigational agent TNX-102 SL for the treatment of fibromyalgia-type long COVID. Topline results for the trial are expected to be announced in the third quarter of 2023.¹

The study, which spans across 30 sites in the US, is a 14-week, double-blind, randomized, placebo-controlled trial that uses change from baseline in the weekly average of daily self-reported worst pain intensity scores as the primary end point. Patients included were between 18 and 65 years, had a polymerase chain reaction confirmed history of SARS-CoV-2 infection at least 3 months prior to enrollment, and had new onset or significant worsening of pain that coincides with a prior COVID-19 infection.

"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," Seth Lederman, MD, chief executive officer, Tonix, said in a statement.¹ "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 fibromyalgia, we are testing TNX-102 SL as a bedtime medicine for the management of Fibromyalgia-type Long COVID."

Fibromyalgia syndrome is characterized by a chronic widespread musculoskeletal pain that frequently is accompanied by fatigue, sleep, cognitive and mood disturbances. Developed by Tonix, 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 the bypass of first-pass hepatic metabolism. It remains in development for other conditions such as alcohol use disorder and Alzheimer disease agitation.

Lederman added, "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. Recently, the U.S. National Institutes of Health (NIH) has identified improving sleep quality as a target for potential therapeutics for Long COVID, consistent with the proposed mechanism of TNX-102 SL."

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In a phase 3, double-blind, placebo-controlled trial published earlier this year, results showed that treatment with TNX-102 SL was associated with significant reductions in daily pain in patients with fibromyalgia. Comprised of 503 individuals, reductions in daily pain at week 14 were significantly greater in the active treated group (least square [LS] mean change, –1.9; 95% CI, –2.1 to –1.7) than placebo (LS mean change, –1.5; 95% CI, –1.7 to –1.3; P = .01). TNX-102 SL was not associated with significant improvement in Patient Global Impression of Change scores, but was associated with improvements in Fibromyalgia Impact Questionnaire Revised scores, Patient-Reported Outcomes Measurement Information System Scores, and daily sleep quality.

"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," Herbert Harris, MD, PhD, executive vice president and head of Translational Medicine, Tonix Pharmaceuticals, said in a statement.¹ "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."

The recently published RECOVER study (NCT), a National Institutes of Allergy and Infectious Diseases-sponsored trial, cluster analysis of the symptom frequencies identified 4 subgroups of Long COVID. Representing approximately one-quarter of the population (28%), this group 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%).³

"We believe Cluster #4 is a subgroup of Long COVID that shares many clinical features with fibromyalgia and may involve common disease mechanisms," Harris added.¹ "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%))."

REFERENCES
1. Tonix Pharmaceuticals completes clinical phase of PREVAIL proof-of-concept study of TNX-102 SL for the treatment of fibromyalgia-type long COVID. News release. August 7, 2023. Accessed August 9, 2023. https://www.globenewswire.com/news-release/2023/08/07/2719562/28908/en/Tonix-Pharmaceuticals-Completes-Clinical-Phase-of-PREVAIL-Proof-of-Concept-Study-of-TNX-102-SL-for-the-Treatment-of-Fibromyalgia-Type-Long-COVID.html
2. Lederman S, Arnold LM, Vaughn B, Kelley M, Sullivan GM. Efficacy and safety of sublingual cyclobenzaprine for the treatment of fibromyalgia: results from a randomized, double-blind, placebo-controlled trial. Arthritis Care Res. Published May 11, 2023. doi:10.1002/acr.25142
3. Thaweethai T, Jolley SE, Karlson EW, et al. Development of a definition of postacute sequalae of SARS-CoV-2 infection. JAMA. 2023;329(22):1934-1946. doi:10.1001/jama.2023.8823