Health Canada Approves Oral Zeposia for Adults With RRMS

Health Canada has approved Zeposia (ozanimod), an oral daily treatment for people with relapsing-remitting multiple sclerosis (RRMS) in the country.

Approval does not assure that Zeposia will be available to Canadian patients at no or low cost, as publicly funded prescription plans are largely administered by each of the country’s 13 provinces and territories.

“Multiple sclerosis is an unpredictable neurological disease that impacts more than 77,000 Canadians. With Canada having one of the highest prevalence rates in the world and no one size fits all approach to treatment, we want to continue seeing innovation and are pleased that there will be another effective oral treatment option,” Pamela Valentine, PhD, president and CEO of MS Society of Canada, said in a press release.

Multiple sclerosis (MS) is caused by the body’s immune system erroneously attacking the nervous system. Zeposia, which is marketed by Bristol Myers Squibb (BMS), is a sphingosine-1-phosphate (S1P) receptor modulator that is believed to work by “trapping” immune cells in lymph nodes. This prevents these cells from entering the nervous system and causing damage.

Zeposia was also approved to treat all relapsing MS forms by the U.S. Food and Drug Administration, and for active RRMS by the European Commission earlier this year.

“This approval reinforces our commitment to transforming patients’ lives and delivering innovative treatment options,” said Al Reba, general manager at Bristol Myers Squibb Canada.

“Bringing to market a new oral treatment option for multiple sclerosis, a disease that impacts so many Canadians, gives us the opportunity to help improve the future for younger higher-functioning MS patients who need to maintain high physical and cognitive ability,” Reba added.

Zeposia’s regulatory approvals were based on positive data from two global Phase 3 clinical trials: SUNBEAM (NCT02294058) and RADIANCE part B (NCT02047734). The trials were conducted across 150 sites in more than 20 countries, and both were sponsored by Celgene, which is owned by BMS.

These trials compared the efficacy and safety of Zeposia to that of Avonex (an injectable formulation of interferon beta-1a, marketed by Biogen) in 2,659 adults, ages 18 to 55, with relapsing MS.

Participants in both trials were treated daily with either one of two doses of Zeposia — 0.92 or 0.46 mg, equivalent to 1 or 0.5 mg of ozanimod hydrochloride, respectively — or with Avonex, administered weekly by intramuscular injection.

Results from the two trials showed that both doses of Zeposia led to significantly greater reductions in annualized relapse rates (the number of relapses per year) compared with Avonex. A pooled analysis of the trials suggested that, relative to Avonex, Zeposia (1 mg) reduced the annualized relapse rate by 48% through one year of treatment, and by 38% through two years.

Zeposia also lowered the number of brain lesions — including new T1 lesions, which represent areas of active inflammation, and new or enlarging T2 lesions, which indicate areas of physical damage to the brain (regardless of current inflammation).

T1 lesions were reduced by 63% after one year and by 53% after two years relative to Avonex. T2 lesions lowered by 48% at one year and 42% after two years.

Zeposia’s use also led to significantly lesser brain atrophy (shrinkage), and to clinically meaningful improvements in participants’ cognitive processing speed.

In Canada, two other oral S1P receptor modulators, both by Novartis, are approved to treat MS: Gilenya (fingolimod) is approved for RRMS, and Mayzent (siponimod) is approved for adults with active secondary progressive MS (SPMS). Of note, it is thought that Zeposia may have a better safety profile than Gilenya, because it is more selective for specific types of S1P receptors.

“Ongoing treatment with disease-modifying therapy in people living with multiple sclerosis can reduce the number of relapses and new brain lesions that form, but each person responds differently to different treatments. This is why having another treatment with meaningful efficacy to help decrease relapses and brain lesions is important,” said Jiwon Oh, MD, an assistant professor of neurology at the University of Toronto.

“Today’s announcement is exciting because it addresses an unmet need for people when first diagnosed with relapsing-remitting MS,” Oh added. “Having an oral treatment with evidence of higher efficacy than some other first-line treatments, and a good safety profile that is well-tolerated to manage clinical exacerbations and whole brain volume loss will be a benefit to people living with MS.”