Phase 2 COMMEND Trial Enrolls ALS Participants After Flex Reports Positive Topline Results

Boston-based Flex Pharma has announced positive topline results from its exploratory Phase 2 trial testing investigational therapy FLX-787 in Australian amyotrophic lateral sclerosis (ALS) patients with frequent muscle cramps.

The data showed that FLX-787 significantly reduced the intensity of cramp-associated pain and stiffness compared to placebo.

The positive results support the drug’s beneficial effects. But since Australia has a limited population of ALS patients, Flex decided to stop the trial and focus on its large U.S.-based Phase 2 COMMEND trial (NCT03196375).

“We are encouraged by the consistently positive impact of FLX-787 across multiple efficacy endpoints related to cramping and associated pain, despite the small number of patients completing the study,” Dr. William McVicar, Flex’s president and CEO, said in a press release.

“These data demonstrate the potential for FLX-787 to benefit ALS patients who suffer from frequent cramping in our ongoing Phase 2b trial, the COMMEND study,” he added. “With data readouts in MS [multiple sclerosis], ALS, and CMT [Charcot-Marie-Tooth] expected over the next year, we are excited to advance the development of FLX-787, under Fast Track designation for ALS-associated cramping.”

Eight of the 12 ALS or primary lateral sclerosis (PLS) patients with frequent muscle cramps enrolled in the trial completed its protocol. This showed that FLX-787 induced a 31 percent decrease in cramps since the beginning of the trial, compared to 0.1 percent of those on placebo.

FLX-787-treated patients remained free from cramps during a median of four days, while placebo controls had cramps every day. Patients’ self-reports showed that FLX-787 treatment improved their outcomes 50 percent of the time, a clear contrast to the 12.5 percent reported in the placebo group.

These results were also confirmed by clinicians who — unaware of the therapy received — determined that half of those treated with FLX-787 showed improvements, compared to zero percent in the placebo group.

“Nearly all ALS patients report cramps, and the majority seek treatment to relieve their suffering from painful cramping and yet there are no approved therapies in the U.S.,” said the company’s chief medical officer, Dr. Thomas Wessel. “This data set provides the first clinical evidence that FLX-787 has an effect in patients with underlying neurological disease and demonstrates the utility of chemical neurostimulation in treating symptoms arising from motor neuron hyperexcitability.”

He added: “In prior studies, FLX-787 has demonstrated similar efficacy profiles in individuals with normally functioning nervous systems such as those suffering from nocturnal leg cramps and healthy normal volunteers studied in our electrically-induced cramp model.”

The COMMEND trial, which is now recruiting participants, will continue to evaluate FLX-787’s efficacy in ALS patients who suffer from cramps. After a 28-day run-in period that will establish patients’ cramp frequency at baseline, they will randomly receive either FLX-787 (30 mg, three times daily) or a placebo for 28 days.

The study’s primary goal is to assess changes in cramp frequency in those treated with FLX-787. Additional parameters evaluated include patients’ global impression of change (PGIC), clinician’s global impression of change (CGIC), cramp-related pain and spasticity, a condition in which muscles are always tight.