FDA Approves Tonmya, First Treatment for Fibromyalgia in Over 15 Years

The FDA approved cyclobenzaprine hydrochloride (HCl) sublingual tablets (Tonmya; Tonix Pharmaceuticals) for the treatment of adults with fibromyalgia. With this action, Tonmya is the first new FDA-approved therapy for this chronic disease in over 15 years, according to the manufacturer’s news release.¹ The approval is supported by findings from the RELIEF (NCT04172831)² and RESILIENT (NCT05273749)³ clinical trials.¹

Tonmya is a nonopioid, sublingual tablet formulation of cyclobenzaprine HCl, which provides rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine. This occurs through first-pass hepatic metabolism. It is a tertiary amine tricyclic and multifunctional agent with binding and antagonist activities at the 5-HT2A serotonergic, α1-adrenergic, H1-histaminergic, and M1-muscarinic receptors. This indication is for a once-daily bedtime treatment for fibromyalgia in adult patients.¹

“The FDA approval of Tonmya as a first-line treatment for fibromyalgia represents a landmark advancement for the millions of people in the US suffering from the debilitating pain this condition causes,” Seth Lederman, MD, CEO of Tonix Pharmaceuticals, said in a news release. “We are hopeful that effectively treating pain with Tonmya could help improve the lives of people with this chronic syndrome.”¹

The RELIEF and RESILIENT clinical trials were double-blind, randomized, placebo-controlled, 2-arm trials that evaluated the efficacy and safety of Tonmya in fibromyalgia. In both trials, the first 2 weeks of treatment consisted of a run-in period in which participants received 2.8 mg (1 tablet) of Tonmya or placebo. Following this 2-week period, all patients increased their dose to 5.6 mg (two 2.8-mg tablets) of Tonmya.^1-3

The primary end point was the daily diary pain intensity score change from baseline to week 14. Secondary end points included global impression of change, Fibromyalgia Impact Questionnaire Revised (FIQR) Symptoms and Function domain scores, Patient’s Global Impression of Change (PGIC) rating, Patient Reported Outcomes Measurement Information System (PROMIS), and daily diary assessment of sleep quality.^2-5

The RELIEF and RESILIENT trials enrolled 503 and 457 adults with fibromyalgia, respectively.^1,4,5 According to study results published in Arthritics Care & Research (Hoboken), the reduction in daily pain from baseline at week 14 was significantly greater with Tonmya (mean change: –1.9; 95% CI, -2.1 to -1.7) compared with placebo (mean change: –1.5 [95% CI, -1.7 to -1.3]; P = .01). Although the investigational treatment was not associated with significant improvement in PGIC at week 14, it was associated with improvements in FIQR scores, PROMIS scores, and daily sleep quality. Overall, approximately 59.7% of Tonmya-treated patients and 46.3% of placebo-treated patients reported treatment-emergent adverse events (AEs), of which the most common were oral hypoesthesia (17.3% vs 0.4%, respectively), oral paresthesia (5.6% vs 0.4%), and abnormal product taste (4.4% vs 0.4%).⁴

Results from the RESILIENT trial, which were published in Pain Medicine, showed that treatment with Tonmya correlated with significantly greater reductions in the primary pain end point (mean change: −1.8) compared with placebo (mean change: −1.2; P < .001), as well as each of the secondary end points (P ≤ .001 in all). The most common systemic treatment-emergent AEs with both Tonmya and placebo were COVID-19 infection (4.3% vs 3.1%, respectively), headache (3.0% vs 1.8%), and somnolence (3.0% vs 1.3%). Like RELIEF, local administration-site reactions included oral hypoesthesia (23.4% vs 0.4%), abnormal product taste (11.3% vs 0.9%), and oral paresthesia (6.9% vs 0.9%), all of which were considered transient and self-limited.⁵

“The chronic pain of fibromyalgia is debilitating to every aspect of a person’s life, including causing sleep disturbance and fatigue, all of which can negatively impact someone’s ability to carry out their daily activities,” Sharon Waldrop, founder of the Fibromyalgia Association, said in the news release. “For over 15 years, this community has been underserved and waiting for new treatment options. This approval is a promising step forward and brings renewed hope to millions.”¹

REFERENCES

1. Tonix Pharmaceuticals. Tonix Pharmaceuticals Announces FDA Approval of Tonmya™ (cyclobenzaprine HCl sublingual tablets) for the Treatment of Fibromyalgia. News release. August 15, 2025. Accessed August 18, 2025. https://ir.tonixpharma.com/news-events/press-releases/detail/1585/tonix-pharmaceuticals-announces-fda-approval-of

2. A Study To Evaluate The Efficacy And Safety Of TNX-102 SL In Patients With Fibromyalgia (RELIEF). ClinicalTrials.gov identifier: NCT04172831. Updated August 8, 2022. Accessed August 18, 2025. https://clinicaltrials.gov/study/NCT04172831

3. A Phase 3 Study to Evaluate the Efficacy and Safety of TNX-102 SL Taken Daily in Patients With Fibromyalgia (RESILIENT). ClinicalTrials.gov identifier: NCT05273749. Updated January 22, 2025. Accessed August 18, 2025. https://www.clinicaltrials.gov/study/NCT05273749

4. 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 (Hoboken). 2023;75(11):2359-2368. doi:10.1002/acr.25142

5. Lederman S, Arnold LM, Vaughn B, Engels JM, Kelley M, Sullivan GM. Pain relief by targeting nonrestorative sleep in fibromyalgia: a phase 3 randomized trial of bedtime sublingual cyclobenzaprine. Pain Med. 2025;pnaf089. doi:10.1093/pm/pnaf089