Following the recent relapsing forms of MS indication revision by the FDA, the unmet need for not active SPMS therapy has been put into stark contrast to other subtypes, while skepticism remains regarding the potential for MedDay Pharmaceuticals’ Qizenday, AB Science’s masitinib, or MediciNova’s ibudilast to emerge as the first-to-market solution, according to Spherix Global Insights
EXTON, Pa., November 14, 2019 ― Following the recent March approvals of Novartis’ Mayzent and EMD Serono’s Mavenclad, Genentech’s Ocrevus continues to dominate neurologists’ stated preference across the three segments of patients with progressive forms of multiple sclerosis (MS): active secondary progressive MS (SPMS), not active SPMS, and primary progressive MS (PPMS). Consistent with perception, data from 751 charts of disease-modifying therapy (DMT)-treated patients with a progressive form of MS (PfMS) provided by 157 neurologists in Spherix’s RealWorld Dynamix™: Progressive Forms of Multiple Sclerosis (US) service confirm that Ocrevus remains the most prescribed DMT for active SPMS and PPMS patients, chosen primarily because of a desire for reduced inflammatory disease activity or delay in disability progression, respectively.
Ocrevus availability and preference contributes to substantial missed share for Novartis’ Gilenya, Genzyme’s Lemtrada, Biogen’s Tysabri, and Mavenclad. As an example, Mavenclad, still early in its launch, could have tripled its current share among DMT-treated PfMS patients. Instead, most of these lost Mavenclad opportunities resulted in new business for Ocrevus as a result of expectations of greater delay in disability progression and the brand’s unique PPMS indication, as well as for Mayzent due to expectations of greater anti-inflammatory efficacy, less safety risk, and greater patient adherence.
Among DMT-treated patients characterized as not active by contributing neurologists, Gilenya, an established S1P receptor modulator, captured more off-label use compared to Ocrevus, potentially foreshadowing neurologists’ initial desire to transition such patients to Novartis’ next-generation S1P receptor modulator, Mayzent, once available. However, while Novartis submitted Mayzent to the FDA seeking a broad SPMS indication, the brand was approved instead for the treatment of relapsing forms of MS (RMS), featuring the first explicit inclusion of active SPMS in that indication. Succeeding the Mayzent approval by just a few days, Mavenclad was also approved for RRMS and active SPMS, although restricted to second or later line. In the months following the approval of these two new market entrants, established DMTs historically approved for RMS had updates to their labels, adding clinically isolated syndrome and active SPMS indications, to be consistent with contemporary nomenclature.
Perhaps due to these label revisions, neurologists estimate that more of their patients have transitioned from relapsing-remitting MS (RRMS) to SPMS compared to prior year estimates. More than two-thirds of neurologists are confident that they are able to identify an RRMS patient who is transitioning to SPMS; these same neurologists are significantly more likely now to agree that DMTs approved for RMS are effective in active SPMS compared to 12 months ago, setting up the segment for a shift in prescribing patterns with the greatly expanded competitive landscape.
Similar to the 2018 audit, switches among SPMS patients were typically driven by efficacy concerns, specifically clinical disability development, with patients having switched from an injectable DMT (i.e., Copaxone) or Biogen’s Tecfidera. Mayzent and (to a lesser degree) the monoclonal antibody DMTs experienced strong net growth as a result of SPMS switching dynamics. In fact, fielded five months post-Mayzent approval, the agent is already the second most-preferred DMT for active SPMS and is a close third for active SPMS brand share after Teva’s Copaxone. Supporting the potential for continued evolution of the SPMS segment away from Ocrevus dominance, if a next-line switch is necessary due to nonresponse to the current DMT, neurologists select Mavenclad, Mayzent, or Lemtrada as the brands most likely to experience a net overall benefit, while Ocrevus share would substantially contract. In the fifth annual edition of RealWorld Dynamix™: DMT Switching in MS (US) fielding in February 2020, Spherix will continue to trend such shifts in switching patterns based upon 1,000+ patients recently switched to a new DMT.
With the approval of Ocrevus for PPMS and the revision of the definition of the RMS indication, not active SPMS (or nonrelapsing SPMS) remains the only subtype with no approved therapies – a stark unmet need which multiple companies are attempting to address through ongoing clinical development programs. MedDay Pharmaceuticals’ Qizenday (MD-1003, high-dose biotin), AB Science’s masitinib, and MediciNova’s ibudilast are all in Phase III pivotal trials for not active SPMS. In fact, prior to patient chart collection for this audit, MediciNova announced that, based upon subgroup analyses of Phase IIb data, the single ibudilast registrational trial would enroll only SPMS patients without relapses, obviously targeting the white space in the MS market. However, based upon currently available data, neurologists do not see much value in the DMT pipeline, even those therapies in development for nonrelapsing SPMS, for their not active SPMS patients.
As an example, only 5% of not active SPMS patients were identified as very likely next-line candidates for ibudilast if nonresponsive to the current off-label therapy. Pivotal trials for pipeline DMTs aiming for the not active indication will need to offer persuasive data to overcome current skepticism related to the potential for efficacy against disability progression in the absence of ongoing inflammatory activity. For the first company and brand to receive FDA approval for not active SPMS based upon such data, Ocrevus’ first-to-market PPMS approval will provide a very realistic analogue for launch with expectations of an increased treatment rate, decreased patient attrition from the treated patient pool, and segment share dominance for the brand.
About RealWorld Dynamix™
RealWorld Dynamix™: Progressive Forms of Multiple Sclerosis (US) is an independent, data-driven service unmasking real patient management patterns through annual reports based on chart audits of ~750 DMT-treated patients diagnosed with a progressive form of MS. The report uncovers the “why” behind treatment decisions, includes year over year trending to quantify key aspects of market evolution, and integrates specialists’ attitudinal & demographic data to highlight differences between stated and actual treatment patterns. Published last week, this is the second annual report covering this segment of the MS market. Parallel US services include RealWorld Dynamix™: New DMT Starts in Multiple Sclerosis (US), fourth annual report publishing in February 2020; RealWorld Dynamix™: DMT Switching in Multiple Sclerosis (US), fifth annual report published in April 2020.
About Spherix Global Insights
Spherix Global Insights is a hyper-focused market intelligence firm that leverages our own independent data and expertise to provide strategic guidance, so biopharma stakeholders make decisions with confidence. We specialize in select immunology, nephrology, and neurology markets.
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