Roche’s Ocrevus and Novartis’ Mayzent may have grabbed headlines as new favorites in multiple sclerosis treatment, but Merck KGaA is also stacking up data to prove its Mavenclad’s worth.
Mavenclad helped keep disability progression at bay in 75% of relapsing-remitting MS (RRMS) patients five years after treatment, a post hoc analysis of phase 3 and extension data showed. Merck reported the data at the European Committee for Treatment and Research in Multiple Sclerosis conference this week.
Among patients treated with Mavenclad during the two years of the Clarity trial, but with placebo in the extension study, 75% remained stable or improved, disability-wise. In those who received the Merck drug in both stages of the study, disability status remained stable or improved in 84% of patients. Changes in median score of a standard disability scale from baseline were similar in both groups.
Currently, the FDA only allows Mavenclad’s use for two years. The Clarity Extension study showed Mavenclad treatment for four years offers similar clinical benefits as the FDA-approved course, only with a higher incidence of lymphopenia, or low levels of white blood cells, a side effect that’s common among MS drugs.
Moreover, analysis of real-world data from an Italian MS registry showed that at five years after receiving the last dose of Mavenclad, 64% of patients had no disability progression and 57% were free of relapse, according to Merck.
“These data show us that Mavenclad continues to display sustained efficacy in a majority of patients at five years after starting treatment and that these results are consistent with data we are seeing from real-world experience,” Gavin Giovannoni, a lead investigator in the Clarity studies, said in a statement.
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Mavenclad’s late-March approval came with some unexpected restrictions. For one, the FDA specifically says the drug is generally recommended only for those who fail on another MS drug and that it’s not for patients with clinically isolated syndrome, a precursor to full-blown MS—both “because of its safety profile.” Except for “the notoriously unsafe Lemtrada,” Mavenclad is the only other MS product being pushed in latter lines, Bernstein analyst Wimal Kapadia noted at that time.
But as Luciano Rossetti, EMD Serono's global head of R&D pointed out, the U.S. boasts high diagnosis rates and high treatment penetration rates, therefore over 80% of relapsing MS patients have already been previously treated with another therapy anyway.
What’s more, the drug’s label bears a boxed warning for a potential increased risk of cancer and birth defects. The latter risk is unique to Mavenclad, even though use of Ocrevus, Sanofi’s Lemtrada, and Biogen’s Tecfidera and Tysabri during pregnancy are also not recommended based on animal data.
In a pooled long-term safety analysis, investigators found no new safety warnings. Cases of malignant tumors were 0.26 per 100 patient years in Mavenclad and 0.12 for placebo. But as Kapadia previously noted, malignancy is linked with many disease-modifying drugs for RRMS, and “therefore is not an absolute reason to see lack of success for Mavenclad,” not to mention there were still doubts on a causal relationship between the drug and cancer.
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The Merck drug does boast a convenience advantage: The tablets are given in two courses, each consisting of only two cycles that each requires daily dosing of just four or five days. Most oral drugs require daily dosing, and Roche’s Ocrevus, which comes as an infusion every six months, is the only one with similar convenience, Kapadia said.
So far, Ocrevus is the clear leader in the MS new drug race, with 2019 first-half sales of CHF 1.74 billion ($1.75 billion), a year-over-year increase of 63% at unchanged exchange rates. Mavenclad, approved in the EU in August 2017, generated €104.7 million ($116 million) during the same period, with about €15 million from North America.
Editor's Note: The story has been updated with additional comment from Merck's Luciano Rossetti.