Ocrevus Still Reigns for Progressive MS, Spherix Reports, But Challenges Noted

Ocrevus Still Reigns for Progressive MS, Spherix Reports, But Challenges Noted
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Genentech’s Ocrevus (ocrelizumab) continues to be the most prescribed treatment for people with progressive forms of multiple sclerosis (MS) among U.S. neurologists, according to the latest Spherix Global Insights’ report.

However, Novartis’ Mayzent (siponimod) “is beginning to close the gap” with Ocrevus among those with active secondary progressive MS (SPMS), a Spherix press release summarizing this report noted.

The report,“RealWorld Dynamix: Progressive Forms of Multiple Sclerosis (US),” was based on 764 charts of progressive MS patients using disease-modifying therapies (DMTs) provided by 169 neurologists across the U.S.

Ocrevus, an anti-CD20 monoclonal antibody administered directly into the bloodstream, was approved in the U.S. to treat active forms of relapsing MS and primary progressive MS (PPMS) — for which it remains the only approved option — in January 2017.

No other DMTs appears close to competing with Ocrevus in the PPMS market, with surveyed neurologists prescribing the therapy to nearly 3 in 5 of these patients, the report found.

Ocrevus was also a common choice across lines of therapy, including as a first DMT, in this patient population. And one-third of PPMS patients reported being open to switching to Ocrevus if the DMT they are currently using proves ineffective.

Across the active SPMS market, Ocrevus continues to hold the top share position “for the third year in a row,” Spherix stated in the release. However, several recently approved DMTs for relapsing MS, which includes active SPMS, may undercut its reign.

Most DMTs are now indicated for all forms of relapsing MS: clinically isolated syndrome, RRMS, and active SPMS. A clear Ocrevus competitor among more recent arrivals, the report stated, is Mayzent — approved in March 2019 as the first oral treatment for SPMS.

Mayzent is now prescribed to nearly 1 in 6 active SPMS patients. Data from the EXPAND study (NCT01665144), the largest Phase 3 clinical trial of SPMS patients to date and one that reported treatment use slowed progression, also makes neurologists consider it “a top contender for active SPMS.”

Neurologists frequently consider Mayzent “the most likely alternative” (aside from other antibody-based DMTs) for their SPMS patients currently prescribed Ocrevus, Spherix stated.

Still, data suggest Ocrevus can expect to continue for some time its reign as the most preferred and commonly prescribed DMT for people with active SPMS.

Neurologists reported high levels of satisfaction to date regarding their active SPMS patients’ responses to Ocrevus, and about two-thirds of active SPMS patients currently on Ocrevus are very unlikely to switch DMTs within the next six months.

“Although well-equipped with clinical trial data, Mayzent faces an uphill battle to meaningfully challenge Genentech’s brand,” Spherix stated in its release.

Ocrevus and Mayzent have distinct mechanisms of action. While Ocrevus promotes immune B-cell depletion, Mayzent works by ‘trapping’ immune cells in lymph nodes (immunological structures), potentially limiting their damaging, pro-inflammatory effect in the brain and spinal cord.

With a similar mechanism of action to Ocrevus — but available as an under-the-skin, at-home, treatment — Novartis’ Kesimpta (ofatumumab), approved in August for all relapsing forms of MS, is another potential competitor for Ocrevus.

Audit data also indicate that half of all progressive MS patients who are “very-likely” candidates for Kesimpta — assuming failure of their current DMT — are diagnosed with active SPMS.

But many of them — more than one-third — are in fact diagnosed with PPMS, suggesting that Kesimpta may draw some PPMS patients away from Ocrevus, should this off-label use allow insurance coverage and reimbursement. Kesimpta’s potential use with PPMS is based on its similarities to the established effects of Ocrevus’ mechanism of action.

Potential treatments still in testing may also come to affect Ocrevus dominance in the field of progressive MS, according to the report.

AB Science’s oral therapy masitinib, which is being developed specifically for non-relapsing SPMS and PPMS, showed a potential to be of greater interest to PPMS patients than Kesimpta as an alternative treatment candidate.

BTK inhibitors such as Sanofi Genzyme’s tolebrutinib (SAR442168) and Genentech’s fenebrutinib might also be future treatments of interest to people with progressive MS. Notably, fenebrutinib will be tested against Ocrevus in a planned Phase 3 trial.

“Although Ocrevus may continue to monopolize the PPMS market in the near future, the numerous ongoing clinical development programs for the treatment of PPMS will begin to open the door for future competition,” Spherix concluded in its release.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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