New Data Support TNX-102 SL Efficacy Ahead of PDUFA

New findings from trials of TNX-102 SL support its efficacy in targeting nonrestorative sleep and improving pain in people with fibromyalgia.1

TNX-102 SL is a sublingual formulation of cyclobenzaprine with a PDUFA goal date of August 15, 2025, to become the potential first member of a new class of non-opioid analgesic drugs for fibromyalgia and the first new drug for treating fibromyalgia in over 15 years.2

These findings, from a phase 1 pharmacokinetic (PK) study and the phase 3 RESILIENT study, were presented in a poster at the European Alliance of Associations for Rheumatology (EULAR) Congress 2025 in Barcelona, Spain, taking place June 11-14, 2025.

“Fibromyalgia is a complex and invisible chronic pain condition which drives many patients to be prescribed chronic opioids which are associated with addiction and overdose,” said Seth Lederman, MD, Chief Executive Officer of Tonix Pharmaceuticals, said in a statement.2 “To address the chronic symptoms of fibromyalgia, potential therapeutic options must provide durable benefits. TNX-102 SL has shown statistically significant, durable activity (14 weeks) in reducing fibromyalgia pain in 2 Phase 3 studies.”

The phase 1 study was a single-center, open-label, randomized, multiple-dose, 2-arm, parallel study (n = 24) comparing the PKs of TNX 102 SL 5.6 mg (2 × 2.8 mg) tablets with Cyclobenzaprine (CBP) HCl Extended-Release (AMRIX; Teva) capsules extended-release (ER) capsules at the maximum recommended daily dose of 30 mg/d.1

“Designed to target the sleep disturbance of fibromyalgia, TNX-102 SL harnesses the therapeutic activity of CBP in part by reducing in the level of the active metabolite norcyclobenzaprine (nCBP) relative to oral cyclobenzaprine. nCBP is believed to interfere with the durability of oral cyclobenzaprine’s treatment effect in off-label chronic dosing regimens and in a failed double-blind randomized placebo-controlled trial,” Lederman said.2 “TNX-102 SL now has the potential to be the first new treatment option for fibromyalgia patients in 15 years.”

In the phase 1 study, lead investigator Iredell W Iglehart III, MD, a physician at a private practice in Baltimore, Maryland, and colleagues found that following the first (Day 1) and last (Day 20) dose of TNX-102 SL 5.6 mg, exposure to CBP and nCBP, was less than with oral CBP capsules. The TNX-102 SL group achieved a higher dynamic peak CBP level at steady state compared with the background level of nCBP. Notably, they found the same 9 phase I metabolites and 8 phase II metabolites in human plasma after both TNX-102 SL and oral CBP dosing.1

The Phase 3 RESILIENT study randomized 457 patients with FM to TNX-102 SL 5.6 mg administered before bedtime (n = 231) or placebo (n = 226). Participants were mostly female (n = 436; 95.4%) and were mostly White/Caucasian (n = 386; 84.5%). They had a mean duration of 9.2 years of FM disease (standard deviation [SD], 9.0) and a mean 5.9 (SD, 1.1) numeric rating scale (NRS) pain score at baseline.

Iglehart and colleagues found that TNX-102 SL demonstrated a highly statistically significant improvement in the primary endpoint of statistically significantly reducing daily NRS pain scores compared with placebo starting at week 1 and continuing until Week 14 (P <.0001), with an effect size of 0.38.1

Furthermore, the key secondary endpoints of Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance, PROMIS fatigue, and diary sleep quality ratings were all found to be statistically significant (all P <.001) compared to placebo, with effect sizes ranging from 0.32–0.50.1

In terms of safety, 81.0% of patients on TNX-102 SL and 79.2% on placebo completed the study, with treatment-emergent adverse events (AEs) leading to discontinuation in 6.1% and 3.6%, respectively. Serious AEs occurred in 2 patients (0.9%) on TNX-102 SL and 3 patients on placebo had serious adverse events, 1 event of acute pancreatitis in the TNX-102 SL group was considered possibly related to treatment. Investigators did not observe any safety signals by vital signs, weight, clinical labs, or physical exams or on C-SSRS or BDI-II.1

REFERENCES

1. Iglehart III I, Sullivan G, Lederman S. Advancing Fibromyalgia Treatment: Transmucosal Sublingual Cyclobenzaprine (Tnx-102 SL) Targets Nonrestorative Sleep and Provides Sustained Pain Reduction.

2. Tonix Pharmaceuticals Presented Data and Analyses of TNX-102 SL Treatment Effects on Fibromyalgia at the Annual European Congress of Rheumatology (EULAR) 2025. News release. Tonix Pharmaceuticals. June 16, 2025. Tonix Pharmaceuticals Presented Data and Analyses of TNX-102 SL Treatment Effects on Fibromyalgia at the Annual European Congress of Rheumatology (EULAR) 2025