Tonix Pharmaceuticals Holding Corp., a company dedicated to the invention and development of next-generation products for fibromyalgia, episodic tension-type headache, and post-traumatic stress disorder (PTSD), recently presented additional data from its completed 12-week, Phase 2b BESTFIT clinical trial in 205 patients treated with Tonmya for fibromyalgia.

Tonmya  is presently being assessed in the Phase 3 AFFIRM clinical trial in 500 patients with a diagnosis of fibromyalgia. As accepted by the FDA, the trial primary endpoint measure is a pain responder analysis, defined as the number of patients who report at least a 30% decrease in their baseline pain at the end of the treatment period of 12 weeks. The company is expecting to report top-line results from this trial during the third quarter of 2016.

Of the 174-fibromyalgia patients who finished the BESTFIT clinical trial, 172 were eligible for the following analyses. Of these, 88-fibromylgia patients received treatment with Tonmya (TNX-102 SL; cyclobenzaprine HCl sublingual tablets, 2.8 mg), and 84 received treatment with a placebo composite.

Data from a tertile analysis of reported improvements in sleep quality were retrieved from 54 fibromyalgia patients who described the highest improvement in sleep quality, or top sleep tertile. These patients were assessed in more detail. Of those fibromyalgia patients assigned in the Tonmya group, 41% were in the top sleep tertile versus 21% in the patients assigned to placebo. Of the 42 patients in the top sleep tertile who reported having experienced at least 30% of improvements in pain from baseline, 67% had been treated with Tonmya versus 33% with placebo.

Results from other analyses assessing sleep quality in the BESTFIT trial revealed a correlation between patient-reported sleep quality and pain improvement as well as broader measures of fibromyalgia impact and clinical symptoms.

These results may corroborate the assumption that improving sleep quality eases pain over time, and is coherent with the growing perception of a reciprocal relationship between chronic, widespread pain and sleep. Non-restorative sleep has been found to be associated with an alteration of brain processes that are believed to be in the cause of certain fibromyalgia symptoms.

“Our new analyses of the BESTFIT data show that those patients who reported the greatest improvement in sleep quality were the most likely to experience pain relief,” Seth Lederman, MD, Tonix’s chairman and CEO, said in a recent news release. “We also observed that the group treated with Tonmya was approximately twice as likely as placebo-treated patients to be in the top third of reported sleep quality improvement. Among all patients in BESTFIT who ranked highest in reported sleep quality improvement, twice as many Tonmya-treated patients experienced at least a 30% improvement in their pain as compared to those treated with placebo.”

These outcomes are integrated within a larger body of results and were recently presented at the 2015 Annual Meeting of the American College of Rheumatology / Association of Rheumatology Health Professionals, held in San Francisco, California, in the format of three posters entitled:

• “Relationship of Sleep Quality and Fibromyalgia Outcomes in a Phase 2b Randomized, Double-Blind, Placebo-Controlled Study of Bedtime, Rapidly Absorbed, Sublingual Cyclobenzaprine (TNX-102 SL).” (abstract no. 2307);
• “Responder Compared to Mean Change Analyses in a Fibromyalgia Phase 2b Clinical Study of Bedtime Rapidly Absorbed Sublingual Cyclobenzaprine (TNX-102 SL).” (abstract no. 2308); and
• “Bedtime, Rapidly Absorbed Sublingual Cyclobenzaprine (TNX-102 SL) for the Treatment of Fibromyalgia: Results of a Phase 2b Randomized, Double-Blind, Placebo-Controlled Study.” (abstract no. 2309).

Tonmya, designed for daily use at bedtime, is believed to have the potential to provide broad therapeutic benefits in fibromyalgia by improving sleep quality as its principal action. Research by Tonix has shown that TNX-102 SL acts on multiple neurotransmitter systems intrinsic to sleep physiology, with potent blocking activity at the serotonin 2A receptor, the alpha-1 adrenergic receptor, and the histamine-1 receptor. The mechanistic profile of TNX-102 SL is distinct from those of products currently approved for fibromyalgia.