The investigational therapy TNX-102 SL (sublingual cyclobenzaprine) had significant beneficial impact on sleep quality and fatigue, although it did not reduce pain levels in patients with fibromyalgia, results from a Phase 3 trial show.
Although these results were disappointing in terms of pain reduction, the trial still demonstrated that TNX-102 SL can have a broad effect on several symptoms related to fibromyalgia.
Supported by these preliminary results and by data from previous studies on people with post-traumatic stress disorder, researchers are planning a new Phase 3 trial to further explore the therapeutic potential of higher doses of TNX-102 SL as treatment for fibromyalgia.
The latest results of the Phase 3 AFFIRM study were recently discussed at the 2019 ACR/ARP Annual Meeting held in Atlanta, in the oral presentation “A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Bedtime Sublingual Cyclobenzaprine (TNX-102 SL) for the Treatment of Fibromyalgia (FM): Evidence for a Broad Spectrum of Activity on the FM Syndrome.”
Current oral cyclobenzaprine-based therapies are mainly limited to short-term use of two to three weeks and are used to relieve muscle spasms and pain or injury.
TNX-102 SL is a new formulation of cyclobenzaprine that was developed by Tonix Pharmaceuticals to overcome some of the limitations of its available forms. It was designed to be absorbed by the body via under-the-tongue (sublingual) administration, resulting in limited toxicity to the liver and reduced exposure to active compounds that may result from cyclobenzaprine breakdown.
Cyclobenzaprine has the potential to inhibit different receptors that are involved in pain, sleep, and stress regulation. Given its broad activity, researchers have been exploring the possibility of using TNX-102 SL as an alternative strategy to manage symptoms related to fibromyalgia syndrome.
The safety and efficacy of a 2.8 mg daily dose of TNX-102 SL was evaluated in 519 patients with fibromyalgia, who were recruited at 35 sites across the U.S. for the Phase 3 AFFIRM (NCT02436096) trial. Participants were randomly assigned to take either TNX-102 SL or a placebo at bedtime for 12 weeks.
An initial evaluation of pain records revealed that the two groups had similar results, with 28.6% of patients in treatment group and 22.6% of the placebo group showing a positive response. This means that the trial did not reach its primary endpoint (response was defined as an improvement of at least 30% from baseline to Week 12 in the weekly average of the daily self-reported average NRS pain severity).
However, more patients in the TNX-102 SL group (22.5%) discontinued the treatment than in the placebo group (13.6%). The researchers stated that an “unexpected imbalance in discontinuations unrelated to efficacy or tolerability” of the treatment “created [a] negative bias in primary responder analysis.”
A new analysis, in which patients who stopped the treatment earlier were not included, showed a positive trend for better pain management in patients treated with TNX-102 SL. Approximately 38.5% of patients treated with TNX-102 SL showed a positive pain response compared with 26.0% in the placebo group.
After 12 weeks of treatment, 23.7% of patients taking TNX-102 SL reported to have experienced significant improvements compared with 16.3% in the placebo group, according to the Patient Global Impression of Change.
The group of patients taking TNX-102 SL also experienced a significant improvement in the Fibromyalgia Impact Questionnaire-Revised scores.
Participants who took daily TNX-102 SL also reported significant improvement in sleep quality since the first week of treatment, and lower fatigue scores were noted beginning in week eight.
Global health assessment also showed significant improvement in physical function at week eight, which was sustained until week 12. However, TNX-102 SL had no effect on Global Mental Health domain.
The most common adverse events of the treatment were oral hypoaesthesia (or numbness, 40.1% vs. 0.8% in the placebo group), glossodynia (painful sensation, 9.2% vs. 1.6%), and paresthesia oral (abnormal sensation, 7.6% vs. 1.2%).
“Improved effects on sleep quality, present within the first week and throughout treatment, support the mechanistic hypothesis that TNX-102 SL has positive effects on fibromyalgia mediated by improvements in sleep quality,” the researchers wrote.
Supported by these clinical results, Tonix Pharmaceuticals is now planning a new Phase 3 trial to assess the efficacy of a 5.6 mg dose of TNX-102 SL in patients with fibromyalgia.
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