• The Food and Drug Administration has approved Merck KGaA’s Mavenclad for the treatment of adults with relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (SPMS).
• Mavenclad is an oral treatment used 10 days a year. Despite that relatively small administration time, the drug’s label is rather restrictive due to safety concerns. Mavenclad can only be administered for two years and not repeated, suggesting its potential market may be relatively small.
• In approving Mavenclad, the FDA also recommended that the drug only be used for patients who have had an inadequate response to, or are unable to tolerate, another drug OK’d for multiple sclerosis. 

Cladribine was initially approved in Europe and the U.S. as an intravenous drug for the treatment of hairy cell leukemia.

Those approvals came in 1993. Just over 15 years later, German Merck submitted Mavenclad (oral cladribine) to the FDA for approval as an RRMS therapy. The drug received a Refusal to File letter from the agency just two months later, however.

Merck KGaA resubmitted Mavenclad in June 2010, but ultimately got hit with a Complete Response Letter requesting a more thorough understanding of the drug’s benefit-risk profile. Following that rejection, the company in June 2011 issued a regulatory update to say it was no longer going to pursue global approval of the tablets for RRMS.

It appears to have had a change of mind, however. Following approvals in 38 countries in 2017 and 2018, including Canada and Australia, the company resubmitted to the FDA its application for Mavenclad, which was accepted for review in July 2018.

While Mavenclad’s approval is a win for Merck KGaA, it also comes with a number of caveats. The label carries a boxed warning against use in pregnant women and in women and men of reproductive age who do not use effective contraception, because of harm to the unborn baby.

Mavenclad also carries an increased risk of cancer. It’s not approved for patients with clinically isolated syndrome, an early stage of MS, and should only be used in patients who can’t tolerate or don’t respond to other MS drugs.

Notably, the approval closely follows an FDA OK of another MS drug, Novartis’ Mayzent (siponimod), which was cleared for both RRMS and SPMS, as well as clinically isolated syndrome.