By Improving Sleep, TNX-102 SL Reduces Pain and Fatigue in Fibromyalgia

Investigators evaluated whether targeting sleep-related neurophysiology with bedtime TNX-102 SL could address multiple core symptoms of the condition.

Image credit: deagreez - stock.adobe.com

Bedtime treatment with TNX-102 SL (Tonmya; Tonix Pharmaceuticals), a sublingual formulation of cyclobenzaprine, significantly improved pain, sleep, fatigue, and overall functioning in patients with fibromyalgia in a phase 3 randomized clinical trial.1 The data, published in Pain Medicine, also showed the treatment was well tolerated.

TNX-102 SL, cyclobenzaprine HCl sublingual tablets, was approved by the FDA to treat fibromyalgia in adult patients in August 2025, making it the first new treatment approved for the musculoskeletal and chronic pain disorder in over 15 years and the fourth treatment approved overall.2

Fibromyalgia is considered the prototypic nociplastic pain syndrome, marked by widespread chronic pain, nonrestorative sleep, fatigue, and impaired daily functioning.1 According to the study, current treatment options remain limited, and many patients experience inadequate symptom relief. Investigators evaluated whether targeting sleep-related neurophysiology with bedtime TNX-102 SL could address multiple core symptoms of the condition.

The double-blind, multicenter, placebo-controlled trial (NCT05273749) enrolled 457 adults with fibromyalgia across 33 US sites between April 2022 and November 2023. Participants were randomized 1:1 to receive once-nightly TNX-102 SL or placebo. Patients in the active treatment group received 2.8 mg nightly for the first 2 weeks, followed by 5.6 mg nightly for 12 weeks. The primary end point was change from baseline to week 14 in weekly average pain intensity, measured using daily numeric rating scale (NRS) diary scores.

Of the 457 randomized patients, 366 (80.1%) completed the trial. Baseline characteristics were well balanced between groups. The mean age was 49.4 years, with a mean fibromyalgia duration of 9.2 years. Most participants were female (95.4%) and White (84.6%), and the average baseline pain score was 5.9 out of 10. Fewer than one-quarter had previously used FDA-approved fibromyalgia therapies.

Results showed TNX-102 SL met the primary end point, producing a significantly greater reduction in pain compared with placebo at week 14. The least squares (LS) mean change in pain was –1.8 with TNX-102 SL vs –1.2 with placebo, corresponding to an LS mean difference of −0.7 (P < .001). Pain improvements with TNX-102 SL were evident as early as week 1 and persisted throughout the treatment period.

Clinically meaningful pain responses were also more common in the TNX-102 SL group. At week 14, 45.9% of treated patients achieved at least a 30% reduction in pain, compared with 27.1% in the placebo group, and 22.5% achieved at least a 50% reduction, compared with 13.3% with placebo.

The treatment demonstrated consistent benefits across multiple secondary end points. Patients receiving TNX-102 SL were significantly more likely to report improvement on the Patient Global Impression of Change. Significant improvements were also observed in the Fibromyalgia Impact Questionnaire–Revised symptoms and function domains, as well as overall impact scores. Measures of sleep disturbance and fatigue, assessed using PROMIS instruments, showed statistically significant improvements, as did diary-reported sleep quality.

Subgroup analyses suggested consistent pain reductions across sex and racial groups, although small sample sizes limited statistical inference in some subpopulations.

TNX-102 SL was generally well tolerated. Treatment-emergent adverse events (TEAEs) occurred more frequently with TNX-102 SL than placebo (58.9% vs 36.7%), but most were mild or moderate. Discontinuation due to TEAEs occurred in 6.1% of TNX-102 SL–treated patients. The most common adverse events were oral cavity–related sensations, such as oral hypoesthesia and taste abnormalities, which typically resolved within 60 minutes. Rates of serious adverse events were low and comparable between groups, with no deaths reported.

“Substantial reduction in pain was achieved by week 1 and continued throughout the study. TNX-102 SL was also associated with significant improvements in each of the 6 prespecified secondary endpoints, suggesting clinically relevant improvements on symptoms of fatigue, sleep disturbance, and global fibromyalgia symptoms and function,” the authors wrote. “Overall, TNX-102 SL was well tolerated with the most common TEAEs being oral cavity AEs related to sublingual administration.”

References

1. 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. 2026;27(1):86-94. doi:10.1093/pm/pnaf089
2. Shaw ML. TNX-102 SL now fourth FDA-approved treatment for fibromyalgia. AJMC®. August 18, 2025. Accessed January 21, 2026. https://www.ajmc.com/view/tnx-102-sl-now-fourth-fda-approved-treatment-for-fibromyalgia