Sativex Does Not Meet Primary Endpoint on Measures of Spasticity for Multiple Sclerosis

Jazz Pharmaceuticals has announced top-line results from the phase 3 RELEASE MSS1 trial, evaluating nabiximols oromucosal spray (JZP378, or Sativex) on clinical measures of spasticity in individuals with multiple sclerosis (MS).

The RELEASE MSS1 trial did not meet the primary endpoint of change in Lower Limb Muscle Tone-6 (LLMT-6) between baseline and day 21, measured by the Modified Ashworth Scale (MAS). The secondary endpoints of the RELEASE MSS1 trial were changes to the LLMT-4 defined by the MAS, safety, and tolerability of nabiximols oromucosal spray in individuals with MS spasticity.

"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. We look forward to additional data from 2 other ongoing trials that have the potential to support a US FDA New Drug Application submission," Rob Iannone, MD, MSCE, executive vice president of global head of research and development at Jazz Pharmaceuticals, said in a statement.

Nabiximols oromucosal spray is a botanical mixture from extracts of cannabis sativa plants, cannabinoids delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as other cannabinoid and non-cannabinoid components. First approved in the United Kingdom in 2010, nabiximols oromucosal has been approved in 29 countries for the treatment of individuals with moderate to severe spasticity due to MS who have not responded adequately to other anti-spasticity medication based on previously completed clinical trials.

The study, the first and smallest of 3 clinical trials in the program, aimed to evaluate the safety and efficacy of nabiximols oromucosal spray in 68 individuals with MS spasticity.

Individuals in the RELEASE MSS1 trial were over 18 years of age with a confirmed diagnosis of any disease subtype of MS for at least 12 months prior to first visit, were expected to remain stable for the duration of the trial, and who experienced spasticity not relieved by their current anti-spasticity medications.

The individuals were randomized in a 1:1 ratio to 1 of 2 sequences comprised of treatment with nabiximols oromucosal spray and the placebo. The data from these trials will be evaluated as it become available and to support the overall registrational program in the United States.

The 2 additional phase 3 trials will complement and inform a comprehensive development plan. In RELEASE MSS3, investigators will evaluate the efficacy of the spray compared to the placebo when added to the standard of care for the improvement of muscle spasms associated with MS over a 12-week treatment period in an estimated 446 individuals.

In RELEASE MSS5, investigators plan to evaluate the effect of multiple doses of nabiximols oromucosal spray compared to the placebo on a clinical measure of velocity-dependent muscle tone in the lower limbs in individuals with MS over a 3-week treatment period in an estimated 190 individuals.

The safety profile in RELEASE MSS1 was consistent with previously reported adverse events and there were no new safety signals in this population.

Reference

Jazz Pharmaceuticals announces top-line results from phase 3 trial evaluating nabiximols oromucosal spray in adult participants with multiple sclerosis spasticity. Jazz Pharmaceuticals. News release. June 28, 2022. Accessed June 30, 2022. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-top-line-results-phase-3-trial