Tecfidera, Gilenya and Ocrevus Losing Favor as Switch Therapies in US, Spherix Finds

Tecfidera (dimethyl fumarate), Gilenya (fingolimod), and Ocrevus (ocrelizumab) are losing ground to more recent therapies among U.S. multiple sclerosis (MS) patients switching treatment, according to the latest Spherix Global Insights’ report.

The launch of MS generics, bioequivalents, and new brands in the U.S. market over the past year has increased competition and promoted “an active switching dynamic,” with patients starting on a new disease-modifying therapy (DMT) “in hopes of an improved outcome,” a Spherix press release summarizing the report noted.

Notably, Genentech’s Ocrevus — administered directly into the bloodstream at hospitals or specialist infusion centers — was the DMT that most lost patients due to COVID-19-related concerns, highlighting that the pandemic “may be the real concern for the brand,” Spherix noted in the release.

The report was part of Spherix’s RealWorld Dynamix: DMT Switching in Multiple Sclerosis (US) service, which has been tracking the switch segment of the country’s MS market for the last six years.

These latest findings were based on chart data from 1,117 MS patients who switched to a different DMT within the past three months, provided by 223 neurologists across the U.S.

Among fumarate agents, Biogen’s well-established, oral treatment Tecfidera lost more patients to other therapies than it gained in new switching clients — which was in sharp contrast to that observed over the previous five years, Spherix noted.

While Tecfidera is still the most prescribed fumarate-based therapy among recently switched patients, Biogen’s Vumerity (diroximel fumarate), approved in the U.S. to treat relapsing forms of MS in 2019, is ready to take its place.

Also given in an oral formulation, Vumerity causes fewer and less severe gastrointestinal side effects relative to Tecfidera, and was the only fumarate-based therapy to have “more patients switching to the brand than away from it,” Spherix stated.

Conversely, both Tecfidera and its generics — nearly identical versions of an original branded medication, typically sold at lower prices — lost shares in the switching setting. Banner Life Sciences’ Bafiertam (monomethyl fumarate), approved in the U.S. as a bioequivalent alternative to Tecfidera in May 2020, showed a good, but low-volume, switch balance.

In the long run, continued Tecfidera decline may have a blowback effect on Vumerity’s rising trajectory, as most of the patients switching to the more tolerable treatment were previously on Tecfidera.

Similar to Tecfidera, Novartis’ well-established Gilenya — a first-generation sphingosine-1-phosphate (S1P) receptor modulator for relapsing MS — is losing net share gains in the market for the first time in six years, with switches away from the therapy outnumbering switches to the brand.

In turn, more patients recently moved to next-generation S1P receptor modulators, Novartis’ Mayzent (siponimod) and Bristol Myers Squibb’s Zeposia (ozanimod) — approved in March 2020 for the same indication.

Notably, Zeposia is thought to have a better safety profile than Gilenya due to its higher selectivity. Bristol Myers Squibb also reports that Zeposia is currently the only S1P receptor modulator not requiring a genetic test or an observation period for most patients being given the first dose.

Most of these switches came from people previously on oral DMTs other than S1P receptor modulators (most frequently Tecfidera).

This suggests that Gilenya’s observed share loss is unlikely due solely to the expansion of the S1P receptor modulator class. Still, the recent March approval of the fourth S1P class member for relapsing MS, Janssen’s Ponvory (ponesimod), will likely challenge Gilenya’s reign even further.

Within the anti-CD20 monoclonal antibody class, recent launches did not appear to affect Genentech’s well-established Ocrevus “to the same extent as seen with the fumarate and S1P receptor modulator classes,” Spherix stated.

While Novartis’ Kesimpta (ofatumumab) — approved in August 2020 as the first self-administered, at-home anti-CD20 monoclonal antibody therapy for relapsing MS — already showed an “impressive share of switches,” Ocrevus maintained its class dominance.

However, Ocrevus’ switch share showed a drop among relapsing-remitting MS (RRMS) patients compared with last year. This may be driven by multiple factors, including Kesimpta uptake, expansion of oral high-efficacy DMT therapies, and COVID-19-related concerns.

“Indeed, COVID-19 played a role in three out of five recent switches away from Ocrevus — higher than that of any other established oral or [anti-CD20 monoclonal antibody] DMT,” Spherix stated.

The report also suggested that Ocrevus may be at least somewhat protected from Kesimpta competition due to its slower uptake among RRMS patients undergoing their first treatment switch, and because most switches to these therapies came from oral DMTs, rather than antibody-based DMTs.

Still, moves from Ocrevus to Kesimpta were common, suggesting that competitive pressure on the first-to-market anti-CD20 monoclonal antibody “may just be beginning to heat up,” Spherix concluded in its release.