Treatment of secondary progressive multiple sclerosis (SPMS) patients with the investigational oral therapy Mayzent (siponimod) significantly reduced the risk of disability progression and decreased inflammation, compared to best supportive care, according to a preliminary draft evidence report from the Institute for Clinical and Economic Review (ICER).
The report and the draft voting questions on clinical evidence, other benefits or disadvantages, and Mayzent’s long-term cost value are open to public comment until 5 p.m. EDT April 10. All interested parties are invited to submit formal comments by email. Details about how to do so are available here.
Based on feedback it receives, ICER may revise its findings in a final evidence report, to be published on May 2. This report will be subject to deliberation in a public meeting of the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), to be held in Rosemont, Illinois, on May 23. Click here to register for the public meeting and the live webcast.
For the preliminary report, ICER, a non-profit watchdog organization, spoke with patients, clinical experts, insurers, and manufacturers.
The assessment compared the effectiveness and safety of Novartis’ Mayzent to that of Tysabri (natalizumab, by Biogen), Ocrevus (ocrelizumab, by Genentech), the interferon beta-1a medications Rebif (by EMD Serono), and Avonex (by Biogen), as well as the interferon beta-1b therapies Betaseron/Betaferon, by Bayer, and Novartis’ Extavia.
Mayzent, currently seeking approval in the U.S. and Europe to treat SPMS, also was compared to best supportive care, which is defined as any intervention not using a disease-modifying therapy and directed toward managing disease symptoms rather than treating its underlying process.
Specifically, the analysis focused on disability progression (as assessed with the Expanded Disability Status Scale), mobility, quality of life, cognitive function, adverse events (side effects), mortality, and other key outcomes.
Mayzent was designed to inhibit the activity of two sphingosine-1-phosphate receptors on the surface of immune cells. The therapy prevents immune cells from migrating to the brain and spinal cord, which reduces the inflammatory reaction that drives SPMS progression.
The team analyzed the results of the multinational Phase 3 EXPAND trial (NCT01665144) testing Mayzent, which included 1,651 SPMS patients with moderate-to-severe disability. The findings showed that, compared to placebo, treatment with 2 mg Mayzent led to a 21% lower rate of disability progression at three months, and 26% at six months.
Also, according to the report, Mayzent lowered the risk of relapse by 46% and the annualized relapse rate — which refers to the number of confirmed relapses per year (0.07 vs. 0.16 with placebo) — lessened the change in brain volume, and also decreased the number of lesions assessed with magnetic resonance imaging.
Benefits also were seen in cognitive processing speed, particularly in patients with relapsing SPMS.
Importantly, the scientists noted the lack of clinical trials comparing the effectiveness of different therapies in SPMS. Performing statistical analyses among different studies also was not possible, given factors such as different study populations and outcome assessments.
Comparing Mayzent to Ocrevus would be particularly important, the scientists noted, due to Ocrevus’ high use in SPMS and perceived effectiveness in the OPERA I and II (NCT01247324 and NCT01412333) trials in relapsing MS patients, and ORATORIO (NCT01194570) in people with primary progressive MS. Ocrevus is the only current treatment available for both relapsing-remitting and primary progressive MS.
As for best supportive care, in comparison, treatment with Mayzent significantly reduced the risk of disability progression and decreased inflammatory disease activity. However, it failed to induce significant positive effects on mobility, cognition, or memory.
Regarding cost-effectiveness, and assuming a similar price to that of Ocrevus, Mayzent showed a cost per additional quality-adjusted life year (QALY) — a measure in which benefits in length of life are adjusted to reflect quality of life — of approximately $826,000, and of approximately $2.5 million per additional life year.
“The cost effectiveness of siponimod was estimated to be approximately $826,000 per QALY gained above best supportive care. Assuming a similar price to ocrelizumab [Ocrevus] as a placeholder, the cost per additional QALY for siponimod [Mayzent] would exceed usual thresholds for cost effectiveness,” the draft report states.
The therapy’s cost effectiveness was more favorable in patients with relapses within two years of study start, leading to lower costs per additional life year and additional QALY — nearly $1.5 million and $396,000, respectively. “This result is influenced by the greater reduction in the risk of disability progression and a greater impact of siponimod on the number of relapses avoided in this subgroup compared to the base case,” ICER’s report states.
“In summary, our analyses indicate that siponimod [Mayzent] improved health outcomes compared to best supportive care,” the report concluded. Of note, the team mentioned that an ongoing seven-year extension study of EXPAND trial may help address the therapy’s long-term benefits and safety, although new trials are needed.