WASHINGTON -- The (Mavenclad) tablets to treat adults with relapsing multiple sclerosis (MS) and active secondary progressive disease late Friday.
The drug is the second oral agent to treat active secondary progressive MS, the first being siponimod (Mayzent), which was approved Tuesday.
Cladribine's approval comes after drug maker Merck KGaA received two rejections from the FDA, the most recent being 8 years ago when the agency said it needed more data about the drug's safety and benefit-risk balance. Cladribine currently is used as a chemotherapy drug (Leustatin) for . A series of studies showed it inhibited activity and proliferation of lymphocytes involved in MS, which prompted Merck KGaA to seek approval for cladribine as a treatment for the disease.
The phase III clinical trial of 1,326 patients with relapsing forms of MS showed that cladribine significantly and reduced the progression of disability compared with placebo. The most common adverse reactions were upper respiratory tract infection, headache, and lymphopenia.
that were reported in the entire cladribine clinical trial program -- which spanned 1,976 patients and 9,509 patient years -- included malignancies (0.27 events per 100 patient-years in treatment arms, compared with 0.13 events per 100 patient-years for placebo), and herpes zoster infections (2.0% vs 0.2%) and oral herpes (2.6% vs 1.2%), according to EMD Serono, the biopharmaceutical business of Merck KGaA.
Cladribine will carry a Boxed Warning for an increased risk of malignancy and fetal harm. It is not to be used in patients with current malignancy.
The drug must be dispensed with a patient medication guide that outlines the drug's risks, including a risk of decreased lymphocytes, an increased risk of infections, and potential hematologic toxicity and bone marrow suppression. Cladribine has been associated with liver injury and with graft-versus-host disease after blood transfusions with non-irradiated blood. Patients of childbearing age should not take the drug unless they plan to use effective contraception during and 6 months after treatment.
Following two treatment courses over a maximum of 20 days during a 2-year period, additional courses of cladribine should not be administered. Re-treatment in years 3 and 4 may further increase the risk of malignancy. The safety and efficacy of re-initiating the drug more than 2 years after completing two treatment courses has not been studied.
Because of its safety profile, cladribine is recommended only for patients who have not responded sufficiently to other MS drugs, and is not recommended for patients with clinically isolated syndrome (CIS).
The FDA nod follows cladribine's approval in more than 50 countries, including the European Union in August 2017.