FDA Approves Cyclobenzaprine Sublingual Tablets for Treatment of Fibromyalgia

The FDA approved cyclobenzaprine HCl sublingual tablets (Tonmya) for the treatment of fibromyalgia in adults. The approval marks cyclobenzaprine as a first-in-class, nonopioid, once daily analgesic with a sublingual formulation that is rapidly absorbed into the bloodstream, and it is the first new FDA-approved therapy for fibromyalgia in over 15 years.¹

Cyclobenzaprine HCl sublingual tablets (Tonmya) are the first new FDA-approved therapy for fibromyalgia in over 15 years. | Image Credit: pathdoc - stock.adobe.com

“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 release¹. “At Tonix, we recognized the transformative potential of pursuing a new approach with Tonmya for fibromyalgia, a chronic overlapping pain condition (COPC) that has gone without innovation for many years. We are hopeful that effectively treating pain with Tonmya could help improve the lives of people with this chronic syndrome.”

The approval was based on 2 phase 3 trials, RESILIENT (NCT05273749) and RELIEF (NCT04172831). In both studies, investigators used a randomized, 14-week study design to evaluate the efficacy and safety of the drug when taken daily at bedtime for the treatment of fibromyalgia. Patients included were aged 18 to 65 years old with a primary fibromyalgia diagnosis and received either the drug or placebo daily for 2 weeks and then 2 tablets daily for 12 weeks.^2,3

The primary end point was change from baseline to week 14 in the daily numerical rating scale weekly average of self-reported average pain severity. The secondary outcomes included the proportion of patients who reported improvements of fibromyalgia at week 14, change from baseline in Fibromyalgia Impact Questionnaire – Revised (FIQ-R) symptoms and function at week 14, change from baseline in patient-reported sleep disturbance and fatigue at week 14, and change from baseline in weekly average sleep quality at week 14.^2,3

Across both trials, the drug significantly reduced daily pain scores compared with the placebo, and a greater percentage of patients receiving cyclobenzaprine experienced clinically meaningful improvements in pain after 3 months when compared with the placebo. Specifically for RELIEF, investigators found that the drug was associated with improved FIQ-R scores, patient-reported outcome scores, and daily sleep quality, but not patient global impression of change, at week 14.

Further, in the study, approximately 59.7% of patients experienced treatment-emergent adverse events (AEs) compared with 46.3% in the placebo group. The most common AEs included oral hypoesthesia, oral discomfort, abnormal product taste, somnolence, oral paresthesia, oral pain, fatigue, dry mouth, and aphthous ulcer.^1,4

“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.¹ “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.”

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REFERENCES

1. Tonix Pharmaceuticals announces FDA approval of Tonmya (cyclobenzaprine HCl sublingual tablets) for the treatment of fibromyalgia. News release. Tonix Pharmaceuticals. 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 phase 3 study to evaluate the efficacy and safety of TNX-102 SL taken daily in patients with fibromyalgia (RESILIENT). ClinicalTrials.gov identification: NCT05273749. Updated January 22, 2025. Accessed August 18, 2025. https://www.clinicaltrials.gov/study/NCT05273749

3. A study to evaluate the efficacy and safety of TNX-102 SL in patients with fibromyalgia (RELIEF). ClinicalTrials.gov identification: NCT04172831. Updated August 8, 2-22. Accessed August 18, 2025. https://clinicaltrials.gov/study/NCT04172831

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