New global trial testing oral therapy BMS-986368 for MS spasticity
Treatment aims to boost body's own processes for easing muscle spasms
A global clinical trial has been launched to evaluate the oral therapy candidate BMS-986368 for treating spasticity — muscle stiffness and spasms — in people with multiple sclerosis (MS).
The Phase 2 study (NCT06782490), called BALANCE-MSS-1, will enroll about 200 adults with MS who have experienced spasticity for at least six months. The planned trial sites are in the U.S., Australia, Canada, Puerto Rico, and across Europe; several are already recruiting.
The trial is sponsored by Celgene and operated by Bristol Myers Squib, which acquired the biopharma company in 2019.
“Physicians who treat muscle spasticity have a limited number of medications from which to choose,” Shahla Hosseini, MD, PhD, professor of physical medicine and rehabilitation at the University of Cincinnati in Ohio, said in a university press release. The university is one of the sites for the trial.
“We really need a new effective treatment for spasticity that’s better tolerated by patients,” Hosseini said.
MS is a neurodegenerative disease in which the immune system mistakenly launches inflammatory attacks against healthy parts of the brain and spinal cord. Among its most common symptoms is spasticity, characterized by muscle stiffness or tightness that makes it hard to move. This may also be accompanied by sudden and involuntary muscle spasms.
As many as 90% of people with MS experience spasticity, which can range from mildly uncomfortable to very painful. It can have a substantial impact on a person’s ability to go about daily life.
There are oral and injectable medications available to ease spasticity, but patients may also rely on strategies like stretching and physical therapy.
Therapy expected to help promote muscle relaxation, ease spasticity in MS
Some medications used for spasticity, such as botulinum toxin products, require injections and, data has shown, may lead to serious side effects. Oral options, including certain muscle relaxants and anti-anxiety medications, can have tolerability issues.
“In the past 20 to 30 years, we haven’t seen development of new effective oral medications to treat spasticity in the United States,” Hosseini said. “The majority of the currently available oral medications have side effects like drowsiness, which limits their usefulness during the daytime.”
Another strategy that’s been explored for MS spasticity is the use of cannabis-based therapies such as nabiximols, an oral spray that is approved in some countries for MS, but is not cleared in the U.S. The compounds in these products mimic the function of a class of naturally occurring molecules in the body called endocannabinoids.
Endocannabinoids regulate a wide range of bodily functions, including mood, pain, and sleep, and are also involved in helping muscles relax.
In the past 20 to 30 years, we haven’t seen development of new effective oral medications to treat spasticity in the United States. … The majority of the currently available oral medications have side effects like drowsiness, which limits their usefulness during the daytime.
BMS-986368 is designed to increase levels of naturally occurring endocannabinoids by inhibiting two enzymes that would normally break them down. By boosting endocannabinoid signaling, the therapy is expected to help promote muscle relaxation and ease spasticity.
“It’s enhancing the natural molecules that are made by the body,” Hosseini said, noting that endocannabinoid levels are sometimes found to be lower than normal in people with MS.
“This finding makes the drug’s mechanism even potentially more relevant to this group if it is able to help normalize their levels of endocannabinoids,” Hosseini added.
Phase 2 trial to test 3 doses of BMS-986368 against a placebo
The Phase 2 trial of BMS-986368 is expected to enroll 200 MS patients, ages 18-70, with spasticity. The participants will be randomly assigned to receive one of three doses of the therapy or a placebo daily for six weeks.
The study’s main goal is to evaluate changes in spasticity levels, as assessed by the Total Numeric-transformed Modified Ashworth Scale-Most Affected Lower Limb score. Other measures of spasticity and physical function, along with BMS-986368’s pharmacological properties and safety, will also be assessed.
After the first six weeks, participants can opt to enroll in a second treatment period, during which all patients will receive one of the three daily doses of BMS-986368 for an additional six weeks.
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