Ocrevus Top Choice of US Neurologists for Active SPMS, But Mayzent and Mavenclad Gaining Interest, Report Says

Genentech‘s Ocrevus (ocrelizumab) continues to be the most prescribed medication to reduce inflammatory disease in people with active secondary progressive multiple sclerosis (SPMS) among U.S. neurologists, even though Novartis’ Mayzent (siponimod) and EMD Serono’s Mavenclad (cladribine) were approved in March to treat this same MS group, according to a 2019 report by Spherix Global Insights.

Ocrevus, the only treatment approved for primary progressive MS, is also the choice for delaying disability progression in people with PPMS.

But Spherix’s latest report, titled “RealWorld Dynamix: Progressive Forms of Multiple Sclerosis (US)” and based on a survey of 157 U.S. neurologists and prescription data they provided, suggests that Mayzent and Mavenclad are gaining on Ocrevus for active SPMS patients.

Mayzent and Mavenclad were the first MS therapies whose U.S. Food and Drug Administration (FDA) approvals explicitly included both active SPMS and relapsing-remitting MS (RRMS) under the umbrella of relapsing MS forms.

Older MS medications subsequently had updates to their labels as well, adding clinically isolated syndrome (CIS) and active SPMS indications to be consistent with the revised definition of relapsing MS.

Possibly influenced by these updates, a shift appears to be underway in how neurologists identify and treat active SPMS patients. These doctors were more likely to estimate that patients had transitioned from RRMS to SPMS in 2019 than they were in last year’s report.

According to a press release summarizing the report, a majority of neurologists surveyed (more than two-thirds) are now confident they can tell if an RRMS patient is transitioning. Compared to one year ago, more are also likely to agree that relapsing MS treatments are effective for active SPMS.

SPMS patients continue to switch their medications mostly due to efficacy concerns, especially in terms of disability progression, the report showed. Many patients switch from an injectable, such as Teva‘s Copaxone (glatiramer acetate) or Biogen‘s Tecfidera (dimethyl fumarate). The use of Mayzent — already the second most-preferred therapy for active SPMS — and biologics (monoclonal antibodies) for these patients has been raising as well.

In fact, neurologists said they favor Mayzent, Mavenclad, or Sanofi Genzyme‘s Lemtrada (alemtuzumab) when a next-line switch is needed in people with active SPMS. (Mavenclad’s approval came with a “general” recommendation that it be a second-line therapy option.) This trend will likely weigh on Ocrevus in this patient group.

Nonactive, or non-relapsing, SPMS is currently the MS type with the greatest unmet need. No approved therapies exist for these patients, in stark contrast to those with other disease types.

Several companies are trying to fill this gap, with clinical development programs ongoing in several investigational treatments. But neurologists remain skeptical about their likely success.

MedDay Pharmaceuticals‘ Qizenday (MD-1003, high-dose biotin), AB Science‘s masitinib, and MediciNova‘s ibudilast are either in or readying Phase 3 trials for nonactive SPMS.

Pivotal trials for MD-1003 (NCT02936037) and masitinib (NCT01433497) are fully enrolled, while ibudilast’s trial has yet to launch.

MediciNova announced that its Phase 3 study — aiming for ibudilast’s approval — would enroll only SPMS patients without relapses, clearly focusing on the high need for therapies here.

However, the neurologists surveyed did not appear to see much value in potential treatments for nonactive SPMS, largely comfortable with off-label therapies. Clinical trials for this SPMS population will need to show compelling data to convince the medical community these treatments effectively slow disability progression in the absence of ongoing inflammation.

Novartis’ Gilenya (fingolimod) is currently more favored for nonactive MS patients than Ocrevus, possibly indicating that neurologists will want to transition patients to Mayzent.

Both Mayzent and Gilenya belong to the same class of medications, that of sphingosine 1-phosphate (S1P) receptor modulators. Ocrevus works through a different mechanism, inducing immune B-cell depletion.