Phase 3 RESILIENT Trial: Tonmya's Role in Non-Opioid Pain Management

The Phase 3 RESILIENT trial demonstrated that TONMYA™ (cyclobenzaprine HCl sublingual tablets) produced a statistically significant reduction in fibromyalgia pain compared with placebo, meeting the prespecified primary endpoint of weekly average pain score at Week 14. The results also showed improvements across multiple symptom domains, including sleep disturbance and fatigue.

RESILIENT was a 14-week, randomized, double-blind, placebo-controlled Phase 3 study conducted at 34 U.S. sites, enrolling 456 intent-to-treat adults who met the 2016 American College of Rheumatology criteria for fibromyalgia. Treatment with TONMYA resulted in a statistically significant reduction in weekly average pain scores at Week 14 versus placebo (p<0.0001), with an effect size of 0.38. The trial also demonstrated significant improvements in key secondary endpoints, including sleep disturbance, fatigue, and the Symptoms and Function domains of the Fibromyalgia Impact Questionnaire-Revised.

TONMYA’s sublingual formulation is designed for bedtime administration and largely bypasses first-pass hepatic metabolism. According to pharmacokinetic data presented, this results in a profile favoring greater relative bioavailability of parent cyclobenzaprine during sleep while reducing daytime exposure to the persistent active metabolite norcyclobenzaprine. This pharmacokinetic differentiation from oral cyclobenzaprine is intended to support activity across core fibromyalgia symptoms.

In safety analyses, TONMYA was generally well tolerated, with minimal effects on weight and blood pressure. Adverse event–related discontinuations occurred in 6.1% of participants receiving TONMYA compared with 3.5% receiving placebo. The most common adverse events were mild and self-limited oral cavity reactions that rarely led to study withdrawal. Serious adverse events were uncommon in the trial population.

TONMYA was approved by the U.S. Food and Drug Administration on August 15, 2025, for the treatment of fibromyalgia in adults. It is the first new prescription medicine approved for fibromyalgia in more than 15 years and represents a centrally acting, non-opioid therapeutic option evaluated in a Phase 3 clinical trial program.

Key Takeaways:

• TONMYA demonstrated a statistically significant and clinically meaningful reduction in weekly average pain at Week 14 in the RESILIENT Phase 3 trial, with additional benefits in sleep and fatigue domains.
• Adults with fibromyalgia meeting established diagnostic criteria—particularly patients with prominent sleep disturbance and those for whom opioid or poorly tolerated therapies are undesired—are the primary beneficiaries.
• Expect bedtime prescribing with once‑daily dosing, monitoring for oral mucosal reactions and serotonergic interactions, and engagement with payers on coverage pathways to integrate TONMYA into formularies and clinical protocols.