FDA Approves Cladribine Tablets—First and Only Short-Course Treatment for Relapsing-Remitting MS

Monday, April 01, 2019


The Food and Drug Administration (FDA) has approved cladribine tablets (Mavenclad; EMD Serono, Rockland, MA) for treatment of relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (SPMS). Cladribine has a dosing schedule that may have a large effect on adherence to treatment. Patients treated with cladribine take the drug (10-20 mg/day, dependent on body weight) for 8 to 10 days over a 2-week period once each year for 2 years. 

In the CLARITY (NCT00641537) trial, 1,976 patients received cladribine treatment with a mean follow up of 4.8 years and a longest follow-up quartile (24%) of 8 years. Cladribine treatment resulted in: 

  • Relative reduction of 58% in annualized relapse rate (ARR) (.14 with cladribine vs .33, < .001) 
  • Increased freedom from relapse over 2 years of treatment (81% with cladribine vs 63% with placebo, < .05) 
  • Reduced 3-month confirmed disability progression on Expanded Disability Status Scale (EDSS)(< .05) 
  • Lower median number of T1-weighted gadolinium-enhanced brain lesions (0 with cladribine vs. 0.33 with placebo < .001)
  • Lower median number of new or enlarging T2 lesions (0 with cladribine vs. 0.67 with placebo, < .001).

Cladribine tablets are recommended for patients who have had inadequate response to, or are unable to tolerate, an alternate drug indicated for treating MS. Cladribine is not recommended for patients with clinically isolated syndrome (CIS). The most common side effects include respiratory tract infection, headache, and lymphopenia. Serious adverse reactions during clinical trials included malignancies (0.27/100 patient years with cladribine vs .13/100 patient-years with placebo) herpes zoster infections (2.0% with cladribine vs 0.2% with placebo) and oral herpes (2.6% with cladribine vs 1.2% with placebo). Safety and efficacy of more than 2 years of cladribine treatment has not been studied.

The mechanism of action for cladribine is not been fully elucidated but is thought to involve cytotoxic effects on B and T lymphocytes through impairment of DNA synthesis, resulting in a dose-dependent reduction in lymphocyte counts followed by recovery. 

"As an investigator in the clinical trial program, I am pleased Mavenclad will now be available to patients in the US. With short treatment courses . . .and no injections or infusions, Mavenclad is an efficacious new treatment option for MS," said Thomas Leist, MD, PhD, Director, Comprehensive Multiple Sclerosis Center at Jefferson University Hospitals, Philadelphia, PA. "Nearly 1 million individuals (have) MS in the US alone, according to a recent National MS Society sponsored study. Mavenclad is a welcome new oral treatment option for this heterogeneous and often unpredictable disease."

June Halper, CEO of the Consortium of MS Centers (CMSC). "People living with MS should have the ability to work with their clinician to choose a treatment with a dosing schedule that supports their lifestyle. CMSC congratulates EMD Serono for their dedication to bring Mavenvlad to the US as the first short-course oral treatment option for the community."

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