Tonix Launches New Phase III Study to Reconcile Mixed Fibromyalgia Data


Eight months after Tonix Pharmaceuticals announced its intentions to halt enrollment in the Phase III RALLY study following a futility analysis of the first 50% of patients, the company announced data that supported that decision.  

Today, New Jersey-based Tonix announced that TNX-102 SL (cyclobenzaprine HCl sublingual tablets) failed to generate a statistically significant outcome in fibromyalgia patients. The study was assessing TNX-102 for the reduction of reducing daily pain after 14 weeks compared to placebo. Interim data first reported in July 2021 indicated that the Tonix asset would not yield the desired results. Based on the recommendation from the Independent Monitoring Committee, Tonix halted enrollment in the clinical program.  

At the time the IDMC made the recommendation, Tonix remained blinded to the study results. The company opted to continue studying patients who had already enrolled until completion, then conduct a full analysis of the unblended data.  

In contrast to the RALLY data, Tonix saw positive results in the Phase III RELIEF study. Data announced in late 2020 showed that TNX-102 SL met the primary endpoint of pain reduction in fibromyalgia, a chronic pain disorder that is believed to result from amplified sensory and pain signaling within the central nervous system.  

Gregory Sullivan, chief medical officer of Tonix, noted the contrasting results between the two studies. He suggested the difference between RALLY and RELIEF may have been driven by the number of patients who discontinued due to adverse events. Sullivan noted there was a 79% increase in adverse event-related participant discontinuation in RALLY patients who received TNX-102 SL compared to RELIEF. However, there was also a 77% increase in adverse event-related discontinuations in the placebo group.  

Seth Lederman, chief executive officer of Tonix, said the company is of the mind that the increased rate of adverse event-related discontinuations could possibly be related to the fact the RALLY study was conducted during the peak of the COVID-19 outbreak in the United States, about the same time the vaccines were being rolled out.  

Lederman added that although TNX-102 SL missed the primary endpoint in RALLY, it continued to show strong activity on sleep disturbance and on the Patient Global Impression of Change, a patient-reported assessment of overall improvement during the trial period. He said the findings from the data, as well as the general understanding of TNX-102 SL tolerability, have encouraged the company to advance its plans for the F307 RESILIENT Phase 3 study for fibromyalgia later this year.  

“Since the pandemic phase of COVID-19 appears to be transitioning to an endemic phase, we believe that starting the new RESILIENT Phase III study imminently is justified based on the expectation that rates of adverse event-related discontinuations will return toward the levels of RELIEF and our PTSD studies,” Lederman said in a statement.  

TNX-102 SL is a sublingual form of cyclobenzaprine hydrochloride. It is designed to provide rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine, due to bypass of first-pass hepatic metabolism, the company said. TNX-102 SL binds and blocks serotonin 2A, alpha1-adrenergic, histaminergic-H1, and muscarinic-M1 receptors. Cyclobenzaprine, the active ingredient of TNX-102 SL, has no recognized potential for addiction, which has made it an appealing asset for development in fibromyalgia. 

It is estimated that fibromyalgia affects between six and 12 million people in the United States, most of whom are women. Disease symptoms include widespread pain, poor sleep habits, fatigue and morning stiffness. Cognitive dysfunction, anxiety and depression are also common symptoms. Approximately one-fourth of FM patients resort to prescription opioids for pain relief. 

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