Phase 2 Study to Evaluate an Oral Drug to Treat MS-related Spasticity and Cramps
Flex Pharma, Inc., announced the start of a Phase 2 clinical trial assessing the safety and efficacy of FLX-787 in multiple sclerosis (MS) patients who suffer from cramps, spasms, and/or spasticity as a result of the disease. The trial is being run in conjunction with Neuroscience Trials Australia.
Flex Pharma’s FLX-787 is a single molecule, chemically synthesized, transient receptor potential (TRP) ion channel activator. The company plans to enroll about 50 adult patients, ages 18 and older, in the randomized and blinded, cross-over trial. In its first part, participants will be given 25 mg of FLX-787 in a beverage each morning and evening for seven days to determine responsiveness. Those found eligible to cross into the second part will be given either the drug followed by a placebo — or the placebo followed by the drug — as a beverage each morning and night for 14 days, with a weeklong “wash-out” period between the two treatments.
The study’s primary endpoints are improvement in spasticity on a self-assessed 10-point scale (the Numerical Rating Scale), muscle responsiveness as measured by the Tardieu Scale, and measures of muscle tone using the Modified Ashworth Scale.
“FLX-787 appears to have virtually no systemic exposure, thus potentially avoiding drug-drug interactions for patients on several prescription products,” Thomas Wessel, MD, PhD, chief medical officer for Flex Pharma, said in a press release.
The drug is capable of interfering with TRPV1 and TRPA1 receptors involved in pain and neurogenic inflammation, the company said in an October 2015 presentation to the Society for Neuroscience’s annual meeting that was reported in Multiple Sclerosis News Today. In that presentation, researchers noted that FLX-787 (either as a single agent molecule or doublet combination) led to a significant reduction in human muscle cramp intensity in a dose-response way, with higher concentrations showing better inhibitory effect.
“Neurologists have very limited therapeutic options for patients suffering from MS spasticity and the current options are often suboptimal due to their associated side effects,” said Al Sandrock, MD, PhD, Biogen’s chief medical officer and a member of Flex Pharma’s Scientific Advisory Board (SAB). “The approach by Flex Pharma offers a potential important advantage as the drug candidate may reduce cramps and spasms without the sedating side effects of many current therapies.”
“We believe that Chemical Neuro Stimulation, the process whereby small molecules activate TRP ion channels topically, leads to sensory stimulation that in turn reduces hyperexcitability in motor neurons,” said Dr. Rod MacKinnon, Flex Pharma’s scientific co-founder, an SAB co-chair, and a Nobel laureate in Chemistry (2003) for his structural and mechanistic studies of ion channels. “We hypothesize that this approach may be generally applicable as a treatment for cramps and spasms in a spectrum of neuromuscular conditions.”
Of the up to 350,000 people in the United States with MS, nearly 84 percent experience spasticity at some point, according to the National Institute of Neurological Disorders and Stroke (NINDS).
“We are encouraged by our recent positive results with the original extract formulation in nocturnal leg cramps (NLC), and we expect to have three human efficacy studies [including in MS] … initiated this year with our single agent candidate, FLX-787,” said Laura Rosen, MD, PhD, vice president of Clinical Research & Drug Safety for Flex Pharma. “I hope our efforts will ultimately help the many patients with severe neuromuscular diseases who suffer from these painful conditions.”