Mayzent, Zeposia May Lose Ground in Canada, Report Finds

Mayzent (siponimod) and Zeposia (ozanimod), the two sphingosine-1-phosphate (S1P) receptor modulators most recently approved in Canada for treating multiple sclerosis (MS), showed strong launches in the country, according to the latest Spherix Global Insights’ report.

However, due to several internal and external factors, sustained relevance of these therapies in the MS market “may be harder to achieve,” a Spherix press release summarizing the report noted.

The report was part of Spherix’s RealTime Dynamix: Multiple Sclerosis (Canada) service, which collects data on market trends of disease-modifying therapies (DMTs) and future expectations through an online survey of 250 neurologists in Canada.

After the established success of Novartis’ first-generation S1P receptor modulator Gilenya (fingolimod) for the treatment of relapsing-remitting MS (RRMS) in Canada, two next-generation S1P receptor modulators — Mayzent, also by Novartis, and Zeposia, by Bristol Myers Squibb — were approved by Health Canada in the past year.

S1P receptor modulators work by “trapping” immune cells in lymph nodes (important immune structures), preventing these cells from entering the nervous system and causing damage.

Mayzent was approved in March 2020 as the first oral treatment for active secondary progressive MS (SPMS), based on data from the EXPAND study (NCT01665144), the largest Phase 3 clinical trial of SPMS patients to date and one that showed the therapy slowed MS progression.

In October 2020, oral Zeposia gained Canadian approval for the first-line treatment of RRMS. Due to its higher selectivity, the third SP1 receptor modulator is thought to have a better safety profile than Gilenya, and was shown to improve cognitive function, in addition to reducing relapse rates and brain lesions.

Zeposia also is currently the only one in its class not requiring a genetic test or an observation period for most patients being given the first dose, according to Bristol Myers Squibb. However, the therapy is still not reimbursed in Canada.

Analyses of Mayzent and Zeposia’s launches in Canada suggest that both therapies “found a place within the treatment armamentarium,” but they may start to lose ground soon, Spherix stated in its release.

Notably, in the past year Mayzent already was associated with a reduction in brand satisfaction and in active SPMS patient candidacy rate. According to Spherix, the therapy may be losing shares to Genentech’s B-cell depleting therapy Ocrevus (ocrelizumab).

Administered directly into the bloodstream, Ocrevus is approved in the country for active RRMS and primary progressive MS (PPMS) — for which there were no approved treatments.

While surveyed neurologists were still more likely to believe that oral Mayzent is superior to into-the-vein Ocrevus in terms of effectiveness and convenience of administration, “the degree to which Mayzent is favored has slipped with each fielding,” Spherix stated.

Given that Gilenya is already under pressure in the RRMS segment due to the launch of its generic — a nearly identical version typically sold at lower prices — Novartis may benefit from broadening Mayzent’s label to include this common MS subtype.

The report noted that almost half of the neurologists had already prescribed Mayzent to at least some RRMS patients and that first-line use of the brand for that indication, while still minimal, increased steadily.

However, such a label expansion would require negotiations with the pan-Canadian Pharmaceutical Alliance to allow Mayzent reimbursement in RRMS patients that have not yet transitioned to SPMS.

Notably, the therapy is approved in the U.S. and in China for treating clinically isolated syndrome and RRMS, in addition to SPMS.

Regarding Zeposia, its unique first-line RRMS label, relative ease of onboarding, and evidence of associated cognitive worsening delay “appear to have helped the brand overcome some of the drawbacks of its third-to-market status,” Spherix stated in the release.

While new DMTs are usually prescribed to patients who failed to respond to other therapeutic options, surveyed neurologists estimated that more than one-third of their patients received Zeposia as their first DMT.

Also, neurologists were three times more likely to state that Zeposia outperforms Gilenya in terms of onboarding ease than the other way around, and Zeposia’s early prescription also appeared to be associated with its protective effects on patients’ cognitive function.

Despite a strong initial uptake, neurologists prescribing Zeposia early in RRMS course do not anticipate additional share growth. To gain some space in the MS market, Bristol Myers Squibb may have to work toward Zeposia reimbursement and an expansion of its prescriber base.

Notably, a fourth S1P receptor modulator may be closer to entering the Canadian MS market: Janssen’s Ponvory (ponesimod), which already is approved in the U.S. and in Europe for the treatment of all forms of relapsing MS.

Pre-launch perceptions and anticipated use patterns among surveyed neurologists showed that prescribers believe that MS patients would benefit from having access to another in-class option.

However, they reported being more likely to prescribe Zeposia over Ponvory for key patient types, supporting the lack of perceived differentiation between the two therapies across all assessed clinical measures.

As such, Janssen may have to focus on Ponvory’s proven clinical superiority over Sanofi Genzyme’s oral Aubagio (teriflunomide) and its positive effects in fatigue to effectively differentiate the brand — “but even then, perhaps with only a receptive subset of Canadian neurologists,” Spherix concluded in its release.