FDA-Approved Medications: New Data on Previously Approved Medications: Oral Medications
Company: EMD Serono
- 3.5 mg/kg divided into two yearly treatment courses of 1.75 mg/kg
- Approved in 2019 for relapsing forms of MS
Mavenclad® (cladribine) is an antimetabolite that reduces the number of lymphocytes, which are white blood cells that are part of the immune system. It long has been used to treat hairy cell leukemia, and regulatory authorities in other countries approved it to treat MS several years before the FDA granted its approval in 2019. The FDA acted later than other regulatory agencies in part because of concerns about Mavenclad potentially increasing the risk of cancer in some patients. Indeed, the prescribing information for Mavenclad includes a boxed warning that the medication may increase risk for malignancy, adding that clinicians should weigh the benefits and risks of treatment on an individual basis, considering a patient’s specific history of, or risks for, cancer.
The prescribing information also notes that, due to its safety profile, “use of Mavenclad is generally recommended for those who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for treatment of MS.” Mavenclad also is contraindicated in pregnant women, and in men and women of reproductive potential who do not plan to use effective contraception. This contraindication stems from concerns about potential birth defects.44
However, new findings provide reassuring news regarding both the safety of Mavenclad and its ability to slow disease progression in people with MS.
Researchers reviewed safety data for 211 patients who received between one and three cycles of Mavenclad. The patients had either relapsing-remitting or progressive MS, and showed disease activity based on magnetic resonance imaging (MRI) scans and measurement of neurofilament light chains (NfL) in cerebrospinal fluid. Patients received three to four 10-mg Mavenclad doses at the start of the study, plus as many as three more 10-mg doses five weeks later if their lymphocytes (a type of infection-fighting white blood cell) were at normal levels. Mavenclad can diminish lymphocytes to dangerously low levels; the manufacturer advises regular blood testing before and during treatment.44
A total of 154 patients completed another cycle of treatment 11 months after the initial cycle. Overall, Mavenclad was well tolerated. Severe lymphopenia (shortage of lymphocytes) occurred in less than 3% of participants, and 12 patients had skin reactions that resolved shortly after treatment. One patient survived a heart attack, and another was diagnosed with breast cancer. Two patients died, but neither death was believed by investigators to be medication-related.
Mavenclad also showed efficacy in slowing MS disease progression. The rate of no evidence of disease activity (NEDA) was 71% among patients with RRMS, and the rate of no evidence of progression or active disease (NEPAD) was 38% among patients with progressive MS. Of 23 patients with elevated NfL initially, 22 had normal levels at follow-up.45