Nabiximols Fails to Meet Trial Goal of Easing Leg Spasticity

The Phase 3 RELEASE MSS1 clinical trial testing nabiximols oral spray failed to meet its primary goal of easing leg spasticity in patients with multiple sclerosis (MS), according to Jazz Pharmaceuticals, the company currently developing the nabiximols clinical program.

Enrolling 68 MS patients, RELEASE MSS1 (NCT04657666) was the first and smallest of three trials in the RELEASE clinical program. The other two trials — RELEASE MSS5 (NCT04984278) and (RELEASE MSS3 (NCT04203498) — are ongoing and data will be evaluated as it becomes available, Jazz reported.

“We remain committed to the nabiximols program and are actively assessing the RELEASE MSS1 trial results, which will be presented at a future medical meeting,” Rob Iannone, MD, executive vice president and global head of research and development at Jazz, said in a press release.

“We look forward to additional data from two other ongoing trials that have the potential to support a U.S. FDA [Food and Drug Administration] New Drug Application submission,” Iannone added.

Nabiximols is an oral spray containing extracts from the cannabis plant, including delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD), two of the plant’s most abundant biologically active constituents. While the mechanisms by which nabiximols works remain poorly understood, it is thought to modulate nerve signaling, leading to muscle relaxation that eases symptoms of spasticity in MS.

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Nabiximols is approved under the brand name Sativex in several countries, including Canada and most of Europe, as an add-on therapy to control involuntary muscle spasms and stiffness in MS patients who failed to respond to other anti-spasticity treatments. The therapy has not received approval in the U.S.

RELEASE MSS1 evaluated the safety and efficacy of nabiximols among 68 adult MS patients with spasticity that was not well-controlled with their current treatments. All participants were monitored for a baseline period of seven days, during which time they used an electronic diary to record spasticity scores and muscle spasms while using their routine anti-spasticity treatments.

Participants then were treated for three weeks with either nabiximols or a placebo. The number of oral sprays was adjusted during the first two weeks, with a maximum of 12 sprays per day. Following treatment, participants’ assigned groups were switched, with those on placebo moving to nabiximols — and vice versa — for another three weeks.

Spasticity was measured by the Lower Limb Muscle Tone-6, or the average of the Modified Ashworth Scale scores in six leg muscles. Jazz now reports that top-line data show the trial failed to meet its main goal of achieving meaningful changes in leg spasticity after treatment.

Safety findings were consistent with previous studies, with no new treatment-related safety signals reported.

“I would like to extend a heartfelt thank you to all those who supported and made this study possible, including the patients who were enrolled, their families, our investigators, staff, and all of the dedicated Jazz employees,” Iannone said.

RELEASE MSS5 will be conducted in a similar format and is expected to enroll an additional 190 participants.

Patients included in RELEASE MSS3 will undergo a 28-day baseline period, prior to being assigned randomly to receive nabiximols or a placebo for 12 weeks. Its main goal is to assess the effects of treatment on daily muscle spasms counts, with secondary measures including changes in mean spasticity scores and safety.

The trial is expected to enroll 446 patients, and is recruiting at sites in the U.S., Czech Republic, Poland, and the United Kingdom.