Tonix Pharmaceuticals Announces Phase 3 RALLY Study Results for TNX-102 SL 5.6 mg for the Management of Fibromyalgia

As Expected Based on Interim Analysis Results Reported in July 2021, TNX-102 SL Did Not Achieve Statistical Significance Over Placebo on the Primary Endpoint of Reduction in Daily Pain in RALLY Study

Relative to the Previous Positive Phase 3 Study (RELIEF), RALLY had an Unexpected Increase in Study Participant Adverse Event-Related Discontinuations in both Drug and Placebo Groups

TNX-102 SL Generally Well Tolerated with Overall Adverse Event Profile Comparable to Prior Studies; No New Safety Signals Observed

Confirmatory Phase 3 Study RESILIENT for the Management of Fibromyalgia Planning to Enroll Participants Imminently

CHATHAM, N.J., March 21, 2022 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that, as expected based on previously reported pre-specified interim analysis results, TNX-102 SL (cyclobenzaprine HCl sublingual tablets)1 did not achieve statistical significance on the primary endpoint of reducing fibromyalgia (FM) daily pain at Week 14 compared to placebo (p=0.115) in the Phase 3 RALLY study. RALLY was a 14-week randomized, double-blind, placebo-controlled trial of TNX-102 SL 5.6 mg, in which 514 participants with FM were randomized in a 1:1 ratio across 36 U.S. sites. All participants received TNX-102 SL 2.8 mg or placebo for the first two weeks, which was increased to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for the remaining 12 weeks. Tonix reported interim analysis results of RALLY in July 2021 at which time the Independent Data Monitoring Committee recommended stopping the study as it was unlikely to succeed on the primary endpoint for the planned full sample. The Company therefore stopped enrollment of new participants while continuing those enrolled at that time to completion.

TNX-102 SL is in mid-Phase 3 development for the management of fibromyalgia. In December 2020, Tonix reported positive results from the Phase 3 RELIEF study of TNX-102 SL 5.6 mg for the management of FM (primary endpoint, p=0.010). FM is a pain disorder characterized by chronic widespread pain, non-restorative sleep, fatigue, and impaired cognition. Approximately one-fourth of FM patients resort to prescription opioids for analgesia2. TNX-102 SL is a centrally acting analgesic that has the potential to be a new non-addictive, non-opioid bedtime medication for the management of FM. Cyclobenzaprine, the active ingredient of TNX-102 SL, has no recognized potential for addiction.

“The positive outcome of the earlier RELIEF study stands in contrast to the missed primary endpoint in RALLY,” said Dr. Gregory Sullivan, M.D., Chief Medical Officer of Tonix. “We believe the difference between these study results may be driven in large part by a 79% increase in adverse event-related participant discontinuations in the drug treatment group in RALLY as compared to RELIEF. Similarly, a 77% increase of adverse event-related participant discontinuations was observed in the placebo group in RALLY as compared to RELIEF.” (Table 1)

TEAE = treatment-emergent adverse event

The missing data for the primary and secondary endpoints were imputed by a method called ‘multiple imputation’ (MI), and discontinuations due to adverse events can negatively impact the statistical outcome when using this approach. Since 2010, The U.S. Food and Drug Administration (FDA) has generally required MI be used to account for missing data in efficacy analyses. Table 2 illustrates how the higher discontinuation rates due to adverse events attenuate the p-values of RALLY using the MI approach.

Table 2: Comparisons of Analytic Methods on Primary and Secondary Endpoints at Week 14 Between the RALLY and RELIEF Phase 3 Studies of TNX-102 SL 5.6 mg in Fibromyalgia