TNX-102 SL Significantly Reduces Daily Pain, Improves Fibromyalgia Symptoms

Seth Lederman, MD

Credit: Tonix Pharmaceuticals

Phase 3 data showed TNX-102 SL (sublingual cyclobenzaprine HCI; Tonmya) significantly reduced daily pain and improved broad fibromyalgia symptoms.

Tonix Pharmaceuticals presented a poster of their pivotal trial, RESILIENT, at the Annual European Congress of Rheumatology (EULAR) 2024 in Vienna, Austria. The study evaluated TNX-102 SL on pain and broad fibromyalgia symptom management.

Approximately 6 – 12 million US adults experience fibromyalgia, living with symptoms of widespread pain, nonrestorative fatigue, and cognitive dysfunction. Individuals with fibromyalgia may struggle with daily activities, have impaired quality of life, and are often disabled.

Research suggests depression, pain-related interference with everyday life, general activity, and cognitive difficulty impact a patient with fibromyalgia’s quality of life more than pain itself. Thus, mood symptoms have a big impact on the quality of life in fibromyalgia.

However, recent research showed TNX-102 SL may improve the nonrestorative fatigue for patients with fibromyalgia, supported by 2 phase 3 trials. TNX-102 SL has potent binding and antagonist activity and several receptors influencing sleep, such as 5-HT2A serotonergic, α1-adrenergic, H1-histaminergic, and M1-muscarinic receptors.

RESILIENT was a randomized, double-blind, multicenter, placebo-controlled study in fibromyalgia. Across 33 US sites, 457 participants with fibromyalgia participated. Fibromyalgia was defined using the 2016 Revisions to the 2010/2011 FM Diagnostic Criteria.

The primary endpoint was the change from baseline to week 14 in the weekly averages of the daily diary average pain intensity score. Key secondary endpoints included Patient Global Impression of Change, Fibromyalgia Impact Questionnaire-Revised (FIQR) Symptoms domain and Function Domain, PROMIS Sleep Disturbance and Fatigue instruments, and daily diary of prior night sleep quality. Other secondary endpoints included Beck Depression Inventory-II (BDI-II), Changes in Sexual Functioning Questionnaire short form (CSFQ-14), Individual symptom items on FIQR Symptoms domain, Seminars in Arthritis and Rheumatism, and earlier timepoints for primary and key secondary endpoints.

The study met the primary endpoint of significant pain reduction compared to placebo on TNX-SL (P = .00005), as well as broad fibromyalgia symptom improvement.

The study also met 6 secondary endpoints with TNX-102 SL significantly improving in areas related to sleep quality (P = .0007), reducing fatigue (P = .00009), and improving patient global ratings (P = .00013), and overall fibromyalgia symptoms (P = .000002) and function (P = .001). The drug was also well-tolerated with comparable adverse event profiles to prior studies.

RESILIENT also demonstrated TNX-102 SL improved depressive symptoms, measured by the Beck Depression Inventory (-0.8; 95% confidence interval [CI], -1.2 to – 0.6; P < .001), with a greater reduction in the TNX-102 SL group than the placebo group by week 14 (P = .005). Compared to placebo, TNX-102 SL also improved female sexual function, measured by the Changes in Sexual Function Questionnaire (P = .010).

“People suffering with fibromyalgia tend to struggle with daily activities, have impaired quality of life, and are frequently disabled,” said Seth Lederman, MD, chief executive officer of Tonix Pharmaceuticals. “We believe the activity of Tonmya on pain, sleep quality, fatigue cognitive dysfunction, and depression are indicative of the broad-spectrum activity of Tonmya, suggesting Tonmya treats fibromyalgia at a syndromal level. We are excited by the prospect of offering this patient population its potential first new therapy option in more than a decade.”

The promising data keeps Tonix on track to submit a New Drug Application (NDA) submission to the US Food and Drug Administration (FDA) in the second half of 2024 for TNX-102 SL for fibromyalgia management.

References

1. ^{Tonix Pharmaceuticals Presented Poster of Tonmya™ for the Management of Fibromyalgia at the Annual European Congress of Rheumatology (EULAR) 2024. GlobeNewswire. June 17, 2024. https://www.globenewswire.com/news-release/2024/06/17/2899616/28908/en/Tonix-Pharmaceuticals-Presented-Poster-of-Tonmya-for-the-Management-of-Fibromyalgia-at-the-Annual-European-Congress-of-Rheumatology-EULAR-2024.html. Accessed June 17, 2024.}
2. ^{Lederman, S. Effects of Bedtime TNX102 SL (Sublingual Cyclobenzaprine HCl) on Mood and Anxiety Symptoms in Fibromyalgia: Results of the Phase 3 RESILIENT Trial. Abstract presented at the American Society of Clinical Psychopharmacology Annual Meeting in Miami on May 29, 2024.}