Sublingual Cyclobenzaprine found to improve Sleep in Fibromyalgia

[Cort]

Fibromyalgia News Today recently reported on data from a large fibromyalgia Phase II drug trial. This drug - a very low dose, sublingual form of flexeril - is believed to be one of four drugs likely to be approved for fibromyalgia in the coming years.

• The Future Fibromyalgia Drugs? Pharmaceutical Source Predicts Four Drug Approvals in Coming Years

The recent reports suggest that the drug - called Tonmya at this point - is on track.

Both Sleep and Pain Improved

As with our IND of TNX-102 SL for fibromyalgia, our goal is to develop a new approach to a common central nervous system disorder with the potential to alter treatment paradigms. Tonix CEO Dr. Seth Lederman

Tonix is moving fast. They reported their clinical trial for Tonmya was filled in June of this year and reported results on the trial last month.

[fleft]

[/fleft]A former study using EEG indicated the drug was increasing restorative sleep, which in turn was associated with reductions in pain, fatigue and depression. In a good sign for those in really severe pain, the most recent studies tied together pain levels and sleep quality; those FM patients in the most pain received the most improvements in sleep quality. Dr. Lederman, Tonix CEO, emphasized that the drug is not a sleeping pill; it doesn't just knock you out - it improves sleep quality.

“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.

The drug fared quite well relative to the placebo - another sign that this drug may ultimately get approved.

“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.”

Novel Approach

The drug's novelty involves the very low dose used and it's sublingual form. The drug is absorbed 10 times more effectively when delivered sublingually than when delivered orally.

Flexeril, the drug Tonmya is derived from, is only effective for a few weeks in reducing muscle spasms. Tonix discovered that cyclobenzaprine - the active ingredient in Flexeril - is converted into a metabolite called norcyclobenzaprine, which builds up in the body when the drug is taken orally. This problem is greatly reduced when the drug is taken sublingually.

The drug appears to be working by affecting down regulating activity in three different systems (serotonin (2A receptor), the sympathetic nervous system (alpha-1 adrenergic receptor) and histamine (histamine-1 receptor.)) The drug's unique approach suggests it's operating differently than any other FM drugs on the market - a good bit of news for FM patients looking for relief.

Tonix believes the drug is reducing both sympathetic nervous system and glutamate (a neuro-excitatory substance) activity. Because SNS functioning and glutamate activity may be increased in chronic fatigue syndrome (ME/CFS), the drug, if approved, willl certainly present new options for ME/CFS patients as well.

It's now onto Phase III trials in 2016, and Tonix hopes - the fourth drug approved for fibromyalgia. Tonix expects the FDA approval to occur in 2017.

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The outcomes were presented via three posters at the 2015 Annual Meeting of the American College of Rheumatology / Association of Rheumatology Health Professionals.

• “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).

 

[loki]

Cyclobenzaprine is a TLR4 inhibitor. Toll-like receptor 4 (TLR4) has been reported to induce microglial activation and cytokines production that contribute to FM symptoms.

 

[Cort]

Cyclobenzaprine is a TLR4 inhibitor. Toll-like receptor 4 (TLR4) has been reported to induce microglial activation and cytokines production that contribute to FM symptoms.

Cool

 

[Paw]

I've been trying 2.5 mg sublingually for a few weeks now. I might be sleeping more soundly, and I think it's eased my RLS. I had been going through an unusually long ME flair-up, but recently have been on the upswing. Hard to say the cyclo is responsible since I've been making some other changes as well, but it sure hasn't hurt.

 

[Cort]

I've been trying 2.5 mg sublingually for a few weeks now. I might be sleeping more soundly, and I think it's eased my RLS. I had been going through an unusually long ME flair-up, but recently have been on the upswing. Hard to say the cyclo is responsible since I've been making some other changes as well, but it sure hasn't hurt.

Thanks for sharing that and good luck with it!