A new sublingual drug that specifically targets nonrestorative sleep, a key feature of fibromyalgia, failed to change average daily pain scores at week 12, the primary endpoint of the study, compared with placebo, a phase 2b trial shows.
On the other hand, TNX-102 SL did lead to improvement in a number of secondary endpoints, including measures of sleep, an effect on pain by a 30% responder analysis (P = .030), as well as the overall burden of symptoms, compared with placebo.
Investigators anticipate that the drug’s effect on nonrestorative sleep in patients with fibromyalgia may improve sleep disturbances in patients with PTSD as well, a disorder in which nightmares are a key feature.
“Our treatment paradigm is that by improving sleep quality, we can improve chronic pain as a secondary benefit,” Seth Lederman, MD, president and chief executive officer, Tonix Pharmaceuticals Holding Corp said.
“And we are gratified that these results cross-validate the paradigm that treating disturbed sleep can provide long-term benefits to fibromyalgia patients.”
Preliminary results of the BESTFIT trial were announced during a press conference held in New York City. Although the data are unpublished, Dr Lederman said there are plans to present more comprehensive results at an upcoming medical meeting.
BESTFIT was a randomized, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of TNX-102 SL. TNX-102 SL contains 2.8 mg of cyclobenzaprine HCL and is administered sublingually.
Patients were instructed to take one tablet at bedtime and were followed for 12 weeks.
Well Tolerated, No Weight Gain
Treatment with active therapy led to statistically significant improvements in key secondary analyses at the end of 12 weeks, as reflected by changes in the Patient Global Impression of Change (PGIC) score (P = .025) and the Fibromyalgia Impact Questionnaire–Revised (FIQ-R) total score (P = .014), compared with placebo.
The most robust effects from TNX-102 SL were seen on sleep.
Table. Outcome Measures at Week 12 (ITT analysis) Compared With Placebo P -value
Daily sleep quality diary Less than .001
PROMIS sleep disturbance 0
FIQ-R sleep quality item Less than .001
Significant improvement was also observed on specific items of the FIQ-R questionnaire, including pain,anxiety, sleep quality, stiffness, sensitivity, and overall symptom subdomain.
“TNX-102 SL was well tolerated,” Dr Lederman added.
The most commonly reported side effects were tongue numbness, which occurred in about 41% of patients on active therapy vs 1% of placebo control patients, and abnormal taste, which occurred in 7.8% of patients receiving TNX-102 SL vs none in the placebo group. Side effects were transient and self-limited.
Somnolence, the most common systemic adverse event, was more common in the placebo group, at 6.9%, compared with 1.9% for the active treatment group.
Importantly, no significant weight gain was seen with TNX-102 SL ― a highly desirable characteristic for a medicine targeting what is a chronic condition, as Dr Lederman observed.
“I think it’s important to recognize that we were the first drug company to bring a sleep treatment program to fibromyalgia, so it’s big news that the nonrestorative sleep hypothesis [in fibromyalgia] has now been confirmed with this drug treatment,” Dr Lederman said.
Potential PTSD Treatment
The company is also interested in exploring TNX-102 SL for the treatment of PTSD.
“In PTSD, sleep disturbance is a big problem, although it’s a bit different from that in fibromyalgia,” Dr Lederman explained.
For starters, sleep disturbances affect both REM and non-REM sleep in PTSD. Individuals with PTSD also commonly experience nightmares during REM sleep in the form of flashbacks of the traumatic event.
“Problems of sleep also correlate with the severity of PTSD,” Dr Lederman added, “and problems with sleep are very important in what some people call the ‘consolidation’ of PTSD, which is the process where acute stress disorder becomes PTSD.”
By improving sleep disturbances in PTSD, the hope is that this consolidation phase of PTSD will be aborted and patients will be spared decades of misery, he added.
As Dr Lederman also pointed out, treatment with TNX-102 SL improved anxiety in the BESTFIT study.
Until the DSM-V was released about 18 months ago, PTSD was considered an anxiety disorder, not a disorder of stress, as it is now defined. “And anxiety is a huge component of PTSD,” Dr Lederman observed.
TNX-102 SL also improved measures of sensitivity in fibromyalgia patients. In fibromyalgia, sensitivity predisposed patients to experience strong reactions to bright lights, loud noises, noxious odors, and the like.
“We believe that what is called sensitivity in fibromyalgia maps to hypervigilance and possibly arousal in PTSD,” Dr Lederman noted.
“And the strong sleep outcome data observed in BESTFIT suggest to us that bedtime TNX-102 SL may be well suited to treating PTSD as well.”
AtEase, a trial of TNX-102 SL in PTSD, is expected to be launched before the end of the year.
Tonix Pharmaceuticals plans to meet with the FDA to review the BESTFIT data and to design an acceptable phase 3 program.