FDA-Approved Medications: Medications Recently Approved
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, including relapsing-remitting disease, and active secondary-progressive disease, in adults.
Mavenclad® (cladribine) has followed a long road to FDA approval for use in MS. Results from its Phase III CLARITY trial were announced in 2009. The trial showed that cladribine 3.5 mg/kg cut the annualized relapse rate (ARR) by 58% relative to placebo over 96 weeks, and that cladribine also had a favorable effect on disability progression, lesion activity on MRI, and other measures of MS activity.24 Clinical trial data also showed that 81% of patients receiving cladribine were free of relapses two years after treatment, compared with 63% of those in the placebo group.2 However, the FDA questioned whether use of cladribine in MS might be associated with an increased risk for cancer, prompting a long-term effort by EMD Serono and its parent company, Merck, to assess the safety of the medication.
EMD Serono ultimately collected data representing 9,500 patient years of cladribine use from people who spent up to eight years in studies. The clinical program found malignancy rates with cladribine use that were low overall but higher than those seen with placebo – 0.27 events per 100 patientyears in patients receiving cladribine versus 0.13 events per patient years in the placebo group. The studies also found higher rates of herpes zoster infection and oral herpes in people receiving cladribine versus those in the placebo group.2 In keeping with those findings, the prescribing information for Mavenclad includes a boxed warning that the medication may increase the risk of 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 patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for treatment of MS.”3 It should be noted that other disease-modifying therapies for MS approved by the FDA include language in their prescribing information concerning a potential increased risk of cancer. Beyond the malignancy concern, Mavenclad 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.
Clinicians considering treatment options for active SPMS or RRMS need to weigh those safety factors against the CLARITY results and follow-up data supporting the efficacy of Mavenclad, as well as the fact that the agent has a different mechanism of action than other MS medications and a short course of treatment. Mavenclad is an antimetabolite that reduces the number of lymphocytes (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 earlier this year. Mavenclad, which is given as tablets, has a two-course treatment regimen. Each course is, in turn, divided into two treatment cycles. In the first course, the drug is administered on Day 1 and then 23 to 27 days later. The second course involves giving tablets at least 43 weeks (approximately 10 months) after the last dose from the first course, and then 23 to 27 days later. After completing this two-course regimen, the medication is not given again during the next two years. The safety and efficacy of reinitiating Mavenclad more than two years after completing two treatment courses has not been studied. [Updated June 2020]