FDA approves Tonmya (cyclobenzaprine HCl sublingual tablets) for the treatment of fibromyalgia – Tonix Pharmaceuticals

Tonix Pharmaceuticals Holding Corp. announced that the FDA approved Tonmya (cyclobenzaprine HCl sublingual tablets) for the treatment of fibromyalgia in adults. Tonmya is a first-in-class, non-opioid, once-daily bedtime analgesic with a unique sublingual (under the tongue) formulation that is designed for rapid absorption into the bloodstream. Tonmya is the first new FDA-approved therapy for the treatment of fibromyalgia in over 15 years.

“The FDA approval of Tonmya as a first-line treatment for fibromyalgia represents a landmark advancement for the millions of people in the U.S. suffering from the debilitating pain this condition causes,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “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 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 the Fibromyalgia Association. “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.”

The approval incorporated efficacy from two double-blind, randomized, placebo-controlled, Phase III clinical trials of nearly 1,000 patients in total that evaluated Tonmya as a bedtime treatment for fibromyalgia. Across both Phase III trials, Tonmya significantly reduced daily pain scores compared to placebo at 14 weeks, the primary endpoint. Additionally, a greater percentage of study participants taking Tonmya experienced a clinically meaningful (≥30%) improvement in their pain after three months, compared to placebo.

Across three Phase III clinical trials with over 1,400 patients evaluated, Tonmya was generally well tolerated. The most common adverse events (incidence ≥2% and at a higher incidence in Tonmya-treated patients compared to placebo-treated patients) included oral hypoesthesia (numbness in the mouth), oral discomfort, abnormal product taste, somnolence (drowsiness), oral paresthesia (tingling, pricking or burning in the mouth), oral pain, fatigue, dry mouth, and aphthous ulcer (canker sore).

“For many years, rheumatologists like myself and other healthcare professionals have had to manage fibromyalgia with limited options that do not adequately meet treatment needs for the majority of patients,” said Philip Mease, M.D., Director of Rheumatology Research at the Providence Swedish Medical Center and Clinical Professor at the University of Washington School of Medicine. “Tonmya is a novel treatment approach that targets nonrestorative sleep that is characteristic of fibromyalgia and can impact core symptoms, specifically pain.”

The latest Phase III trial, RESILIENT, was recently published in Pain Medicine with data on primary and secondary endpoints measuring pain, patient’s global impression of change, patient-reported symptoms and function, sleep disturbance, and fatigue (see citation below).

“I know firsthand how the chronic pain of fibromyalgia significantly disrupts my patients’ lives.” Andrea L. Chadwick, M.D., MSc, FASA, Anesthesiology, Pain, and Perioperative Medicine at The University of Kansas Health System. “Treatments that are processed through the liver can result in metabolites that could affect a medicine’s efficacy and safety over time. Tonmya is administered sublingually which is designed to reduce pain quickly and durably with a tolerable safety profile.”

Tonmya is expected to be available for adult patients in the U.S. with fibromyalgia beginning in the fourth quarter of this year.

About the Phase III Clinical Trials: RELIEF and RESILIENT
The RELIEF and RESILIENT studies were double-blind, randomized, placebo-controlled trials designed to evaluate the efficacy and safety of Tonmya (cyclobenzaprine hydrochloride sublingual tablets) for the treatment of fibromyalgia. RELIEF and RESILIENT were two-arm trials that enrolled 503 and 457 adults with fibromyalgia across 40 and 33 United States sites, respectively. In both trials, the first two weeks of treatment consisted of a run-in period in which participants started on Tonmya 2.8 mg (1 tablet) or placebo. Thereafter, all participants increased their dose to Tonmya 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for the remaining 12 weeks. The primary endpoint across both trials was the daily diary pain intensity score change (Tonmya 5.6 mg vs. placebo) from baseline to Week 14 (using the weekly averages of the daily numerical rating scale scores). Additional details on RELIEF (NCT04172831) and RESILIENT (NCT05273749) are available on clinicaltrials.gov.

RALLY was a replicate Phase III trial to RELIEF and RESILIENT that demonstrated greater but non-significant treatment effect with Tonmya compared to placebo and demonstrated consistent safety. Results of this trial may not have been generalizable due to the presence of factors outside the conduct of the study. Additional details are available on clinicaltrials.gov (NCT04508621).

Citation: Pain Relief by Targeting Nonrestorative Sleep in Fibromyalgia: A Phase III Randomized Trial of Bedtime Sublingual Cyclobenzaprine. Authors: Seth Lederman, MD , Lesley M Arnold, MD , Ben Vaughn, MS et al. Pain Medicine, pnaf089, https://doi.org/10.1093/pm/pnaf089 Published: 08 July 2025