TNX-102 SL Now Fourth FDA-Approved Treatment for Fibromyalgia

TNX-102 SL (Tonmya; Tonix Pharmaceuticals), cyclobenzaprine HCl sublingual tablets, has been approved by the FDA to treat fibromyalgia in adult patients, making it the first new treatment approved for the musculoskeletal and chronic pain disorder in over 15 years and the fourth treatment approved overall.¹

TNX-102 SL now joins pregabalin caplets (Lyrica; Viatris) approved in 2007,² duloxetine capsules (Cymbalta; Eli Lilly) approved in 2008,³ and milnacipran tablets (Savella; AbbVie) approved in 2009.⁴

This newest approval is based on the significant reductions in fibromyalgia-related pain seen in the phase 3, double-blind, randomized, placebo-controlled RELIEF trial (NCT04172831) that concluded in 2020 and RESILIENT trial (NCT05273749) that concluded in 2023.^5,6 Results from both trials also demonstrated good tolerance of the treatment, as did a third trial, RALLY (NCT04508621)⁷; however, also in RALLY, TNX-102 SL demonstrated a nonsignificant greater treatment effect vs placebo and these data were not considered in this approval.¹

“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,” said Sharon Waldrop, a person with lived experience and founder of Fibromyalgia Association, in a statement.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.”

This approval brings the total to 4 of medications approved to treat fibromyalgia; in addition to cyclobenzaprine HCl sublingual tablets, there are pregabalin (Lyrica), duloxetine (Cymbalta), and milnacipran (Savella). | Image Credit: © wladimir1804-stock.adobe.com

Patients started on a run-in dose of 2.8-mg TNX-102 SL or placebo for their first 2 weeks of treatment, after which those in the treatment arm were increased to 5.6 mg split evenly across 2 tablets, or placebo tablets were continued for 12 additional weeks, in the RELIEF and RESILIENT trials. The primary end point was change in daily diary pain intensity score from baseline to week 14. More than 95% of patients in each trial were female, and more than 84% in each trial were of White race.^5,6

In RELIEF, the mean (SD) reduction in pain intensity score was 1.9 (95% CI, –2.1 to –1.7) in the treated group compared with 1.5 (95% CI, –1.7 to –1.3) among those who received placebo.⁵ In RESILIENT, the corresponding pain intensity score reductions were 1.8 (95% CI, –2.0 to –1.6) and 1.2 (95% CI, –1.4 to –0.9).⁶ Looking also at Patient’s Global Impression of Change rating of “very much improved” or “much improved” by week 14, 37.5% of patients in RELIEF and 28.6% of patients in RESILIENT demonstrated this positive outcome compared with 29.4% and 15.1% of placebo-treated patients, respectively.^5,6

Additional data show reductions of 18.4 (95% CI, –10.8 to –16.0) vs 14.0 (95% CI, –16.4 to –11.7) and 16.0 (95% CI, –18.3 to –13.7) vs 8.4 (95% CI, –10.7 to –6.1) in RELIEF and RESILIENT, respectively, in change from baseline in Fibromyalgia Impact Questionnaire–Revised (FIQ-R) Symptoms Domain Score, and 13.6 (95% CI, –16.1 to –11.2) vs 9.3 (95% CI, –11.7 to –6.8) and 12.2 (95% CI, –14.5 to –9.9) vs 6.8 (95% CI, –9.2 to –4.4) in FIQ-R Function Domain Score. Changes from baseline in the Patient Reported Outcomes Measurement Information System (PROMIS) score for sleep disturbance, PROMIS fatigue, and weekly average of daily diary assessment of sleep quality were also investigated.

The most common adverse events, reported for at least 2% and which occurred in more patients treated with TNX-102 SL vs placebo, were oral hypoesthesia, oral discomfort, abnormal product taste, somnolence, oral paresthesia, oral pain, fatigue, dry mouth, and aphthous ulcer (canker sore).¹ TNX-102 SL is contraindicated for use in patients with hypersensitivity to cyclobenzaprine or any inactive ingredient in this treatment, with concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days of discontinuing an MAO inhibitor, for those in the acute recovery phase of a heart attack, and in the presence of hyperthyroidism. Female patients are advised to use contraception during treatment and for 2 weeks after their final dose, due to the potential for neural tube defects, and caution is recommended for patients with a history of seizure disorder because cyclobenzaprine is structurally related to tricyclic antidepressants, which are known to lower the seizure threshold. There are additional warnings regarding atropine-like effects, central nervous system depression, serotonin syndrome, and oral mucosal adverse reactions.

The first-in-class nonopioid is taken once daily at bedtime, with the sublingual form able to be rapidly absorbed into the bloodstream, meaning quicker relief for patients, approximately 10 million of whom live in the US.¹ Close to 1000 patients participated in the RELIEF (n = 503)⁵ and RESILIENT (n = 457)⁶ trials, and factoring in those who participated in RALLY (n = 514), more than 1400 patients were evaluated across the 3 studies.

TNX-102 SL is expected to enter the market and become commercially available in the US in the fourth quarter of 2025, where it will retain market exclusivity until at least 2034.¹

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. Pfizer's Lyrica receives FDA approval for fibromyalgia based on expedited review. News release. Pfizer. June 21, 2007. Accessed August 18, 2025. https://www.pfizer.com/news/press-release/press-release-detail/pfizer_s_lyrica_receives_fda_approval_for_fibromyalgia_based_on_expedited_review
3. FDA approves Cymbalta for the management of fibromyalgia. News release. Eli Lilly. June 16, 2008. Accessed August 18, 2025. https://investor.lilly.com/news-releases/news-release-details/fda-approves-cymbaltar-management-fibromyalgia
4. Forest and Cypress announce FDA approval of Savella for the management of fibromyalgia. News release. January 14, 2009. Accessed August 18, 2025. https://www.fiercebiotech.com/biotech/forest-and-cypress-announce-fda-approval-of-savella-tm-for-management-of-fibromyalgia
5. A study to evaluate the efficacy and safety of TNX-102 SL in patients with fibromyalgia (RELIEF). ClinicalTrials.gov. Updated August 8, 2022. Accessed August 18, 2025. https://clinicaltrials.gov/study/NCT04172831
6. A phase 3 study to evaluate the efficacy and safety of TNX-102 SL taken daily in patients with fibromyalgia (RESILIENT). ClinicalTrials.gov. Updated January 22, 2025. Accessed August 18, 2025. https://clinicaltrials.gov/study/NCT05273749
7. A phase 3 study to evaluate the efficacy and safety of TNX-102 SL in patients with fibromyalgia (RALLY). ClinicalTrials.gov. Updated December 18, 2023. Accessed August 18, 2025. https://clinicaltrials.gov/study/NCT04508621