TNX-102 SL · program

TNX-102 SL (cyclobenzaprine HCl sublingual) for Fibromyalgia

ApprovedApprovedTonix Pharmaceuticals Holding Corp. (TNXP)
  • Fast Track

Indications for TNX-102 SL: Fibromyalgia · Approved Acute Stress Disorder · Phase 2 Major depressive disorder · Phase 2 Post-traumatic stress disorder · Discontinued

Lead, FDA-approved indication for TNX-102 SL (sublingual cyclobenzaprine HCl), marketed as TONMYA. On 15 August 2025 the FDA approved Tonmya for the treatment of fibromyalgia in adults — the first new FDA-approved fibromyalgia therapy in more than 15 years and a first-in-class non-opioid, once-nightly bedtime analgesic. Recommended dosage is 5.6 mg (two 2.8 mg sublingual tablets) once daily at bedtime, titrated from one 2.8 mg tablet for the first 2 weeks. The therapeutic rationale is bedtime treatment of non-restorative sleep to reduce the chronic widespread (nociplastic) pain of fibromyalgia, via cyclobenzaprine's multifunctional antagonism at 5-HT2A, H1, alpha-1 and M1 receptors. Approval was supported by two double-blind, randomized, placebo-controlled pivotal Phase 3 trials enrolling ~960 patients combined: RELIEF (NCT04172831; topline 7 Dec 2020; primary endpoint of Week-14 reduction in daily diary average pain NRS met, p=0.010) and RESILIENT (NCT05273749; topline 20 Dec 2023; p=0.00005, with significance across all six key secondary endpoints; published in Pain Medicine, 9 Jul 2025). FDA granted Fast Track designation for fibromyalgia (announced 25 Jul 2024); the NDA was accepted on 17 Dec 2024 with a PDUFA action date of 15 Aug 2025. Tonix's broader fibromyalgia program also included an earlier Phase 2b study (AFFIRM) and a Phase 3 RALLY study (NCT04172843) that was stopped at a pre-planned interim analysis for futility; only the two approval-enabling pivotal trials are tracked here.

Data current as of

Development timeline

ApprovedAug 2025
  1. metFDA approved Tonmya (TNX-102 SL) for fibromyalgia in adults — first new fibromyalgia drug in over 15 years.↗
Filed (NDA)Dec 2024
  1. FDA accepted the filing of the New Drug Application (NDA) for TNX-102 SL for fibromyalgia; a PDUFA target action date of 15 Aug 2025 was subsequently assigned.↗
Phase 3Dec 2020 – Jul 2024
  1. FDA granted Fast Track designation to TNX-102 SL (Tonmya) for the management of fibromyalgia (announced 25 Jul 2024).↗
  2. metSecond Phase 3 RESILIENT met its primary endpoint with high significance (p=0.00005); all six key secondaries positive.↗
  3. metPhase 3 RELIEF met its primary endpoint: TNX-102 SL 5.6 mg significantly reduced fibromyalgia pain at Week 14 (p=0.010).↗

Readouts

  • 2025-08-15ReportedRegulatorymet

    FDA approved Tonmya (TNX-102 SL) for fibromyalgia in adults — first new fibromyalgia drug in over 15 years. ↗

  • 2023-12-20ReportedTopline datametNCT05273749

    Second Phase 3 RESILIENT met its primary endpoint with high significance (p=0.00005); all six key secondaries positive. ↗

  • 2020-12-07ReportedTopline datametNCT04172831

    Phase 3 RELIEF met its primary endpoint: TNX-102 SL 5.6 mg significantly reduced fibromyalgia pain at Week 14 (p=0.010). ↗

Clinical trials in Fibromyalgia

NCT05273749TNX-CY-F306Phase 3Completedn=457

A Phase 3, Double-Blind, Randomized, Multicenter, Placebo-Controlled Study To Evaluate The Efficacy And Safety Of TNX-102 SL Taken Daily At Bedtime In Patients With Fibromyalgia (RESILIENT)

Started Apr 2022· Primary completion Nov 2023

metprimaryChange from baseline to Week 14 in weekly average of daily self-reported average pain severity (NRS), TNX-102 SL 5.6 mg vs placebo — LS mean -1.8 (TNX-102 SL) vs -1.2 (placebo); difference -0.7 (0.00005)

Second, confirmatory pivotal Phase 3 trial (33 US sites). Primary endpoint met with high statistical significance: TNX-102 SL 5.6 mg at bedtime reduced daily pain at Week 14 vs placebo (LS mean -1.8 vs -1.2, difference -0.7, p=0.00005). Statistically significant improvements across all six prespecified key secondary endpoints (PGIC responder, FIQR Symptoms and Function domains, PROMIS Sleep Disturbance and Fatigue). Published in Pain Medicine, 9 Jul 2025. Together with RELIEF this trial supported the NDA and 15 Aug 2025 FDA approval.

NCT04172831TNX-CY-F304Phase 3Completedn=503

A Phase 3, Double-Blind, Randomized, Multicenter, Placebo-Controlled Study To Evaluate The Efficacy And Safety Of TNX-102 SL Taken Daily At Bedtime In Patients With Fibromyalgia (RELIEF)

Started Dec 2019· Primary completion Oct 2020

metprimaryChange from baseline to Week 14 in weekly average of daily self-reported average pain severity (NRS), TNX-102 SL 5.6 mg vs placebo — LS mean -1.9 (TNX-102 SL) vs -1.5 (placebo) (0.010)

First pivotal Phase 3 trial (40 US sites). Primary endpoint met: TNX-102 SL 5.6 mg at bedtime significantly reduced daily pain at Week 14 vs placebo (LS mean change -1.9 vs -1.5, p=0.010), with a greater proportion achieving >=30% pain improvement and activity on key secondary endpoints of sleep quality, fatigue and FIQR global symptomatic/functional recovery. Most common adverse event was transient oral/tongue numbness at the administration site.

Formulations

FormulationRouteRegimenPharmacokinetics
TNX-102 SL (TONMYA) sublingual tabletsublingual transmucosal disintegrating tablet (bypasses hepatic first-pass metabolism, reducing formation of the long-half-life metabolite norcyclobenzaprine)
2.8 mg starting dose (days 1-14); 5.6 mg target dose (two 2.8 mg tablets, day 15+) once daily at bedtime; maximum 5.6 mg/day
SublingualOnce nightlyt½ 36 h · Tmax 4.3 h

Mechanism of action (compound-wide)

Cyclobenzaprine is a multifunctional, centrally acting antagonist at several aminergic GPCRs. Reported high-affinity radioligand-binding antagonism at histamine H1 (Ki ~1.3 nM), serotonin 5-HT2A (Ki ~5.2 nM), alpha-1A adrenoceptor (Ki ~5.6 nM) and muscarinic M1 (Ki ~7.9 nM) receptors. In PTSD the therapeutic hypothesis is that bedtime H1/5-HT2A/alpha-1 antagonism improves sleep quality and reduces hyperarousal, with potential disease-modifying effects on sleep-dependent trauma processing. The sublingual formulation is designed to limit the long-lived active metabolite norcyclobenzaprine.

TargetActionAffinity
H1 receptorprimaryHRH1AntagonistKi 1.3 nMⓘ
5-HT2AHTR2AAntagonistKi 5.2 nMⓘ
alpha-1A adrenoceptorADRA1AAntagonistKi 5.6 nMⓘ
M1CHRM1AntagonistKi 7.9 nMⓘ

← Full TNX-102 SL compound page (identity, identifiers, all indications)

Sources

  1. Cyclobenzaprine and Its Major Metabolite Norcyclobenzaprine Are Potent Antagonists of Human 5-HT2A, H1 and alpha-Adrenergic Receptors (Daugherty, Gershell, Lederman) — ACR/ARHP Annual Meeting (American College of Rheumatology), 2012
  2. RELIEF: Phase 3 study of TNX-102 SL in fibromyalgia (NCT04172831) — ClinicalTrials.gov
  3. RESILIENT: Phase 3 study of TNX-102 SL in fibromyalgia (NCT05273749) — ClinicalTrials.gov
  4. The Skeletal Muscle Relaxer Cyclobenzaprine Is a Potent Non-Competitive Antagonist of Histamine H1 Receptors — Journal of Pharmacology and Experimental Therapeutics (JPET), 2024
  5. Tonix Pharmaceuticals Announces FDA Acceptance of the NDA for TNX-102 SL for Fibromyalgia (PDUFA 15 Aug 2025) — Tonix Pharmaceuticals / IR
  6. Tonix Pharmaceuticals Announces FDA Approval of Tonmya (cyclobenzaprine HCl sublingual tablets) for the Treatment of Fibromyalgia — Tonix Pharmaceuticals / IR
  7. Tonix Pharmaceuticals Announces Highly Statistically Significant Topline Results in Second Phase 3 (RESILIENT) Trial of TNX-102 SL for Fibromyalgia (p=0.00005) — Tonix Pharmaceuticals / IR
  8. Tonix Pharmaceuticals Announces Positive Phase 3 RELIEF Study Results for TNX-102 SL 5.6 mg in Fibromyalgia (p=0.010) — Tonix Pharmaceuticals / IR
  9. Tonix Pharmaceuticals Granted Fast Track Designation by FDA for Tonmya for Fibromyalgia — Tonix Pharmaceuticals / IR
  10. TONMYA (cyclobenzaprine hydrochloride sublingual tablets) FDA Prescribing Information — DailyMed / U.S. FDA