ROCKLAND, Mass.—EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada, has announced that a resubmission of the New Drug Application (NDA) for cladribine tablets as a potential treatment for patients with relapsing forms of multiple sclerosis (MS) has been accepted for filing by the U.S. Food and Drug Administration (FDA). Cladribine is an investigational agent that has been studied as a short-course (a maximum of 20 days of treatment over two years) oral therapy that is thought to selectively target lymphocytes, which may be integral to the pathological process of relapsing MS.

The NDA acceptance follows global approvals of cladribine tablets under the trade name Mavenclad in 38 countries since August 2017, including the European Union (EU), Canada, Australia, Israel, Argentina, United Arab Emirates, Chile and Lebanon. In December 2017, Health Canada and the Therapeutic Goods Administration (TGA) in Australia approved Mavenclad for the treatment of relapsing-remitting MS. Additional filings in other countries are planned for 2018.

The acceptance indicates that the FDA has found the Company’s resubmission sufficiently complete to permit a substantive review. The resubmission is in response to the Complete Response Letter issued by the FDA in 2011 requesting an improved understanding of safety risks and the overall benefit-risk profile.

 

“We are delighted the FDA has accepted cladribine tablets for filing,” said Belen Garijo, Member of the Executive Board and CEO Healthcare of Merck KGaA, Darmstadt, Germany. “Our goal is to offer cladribine tablets to patients and physicians in the U.S. as a new treatment paradigm for relapsing MS, and we look forward to working closely with the FDA throughout the review process.”

 

The NDA acceptance includes close to 12,000 patient years of data with over 2,700 patients included in the clinical trial program, and up to 10 years of safety data in some patients. The clinical development program included data from three Phase III trials, CLARITY, CLARITY EXT and ORACLE MS, the Phase II ONWARD study and long-term follow-up data from the eight-year prospective registry, PREMIERE. In the two-year CLARITY study, the most commonly reported adverse event (AE) in patients treated with cladribine tablets was lymphopenia. The incidence of infections was 48.3% with cladribine tablets and 42.5% with placebo, with 99.1% and 99.0% respectively rated mild-to-moderate by investigators.

 

“Most available MS therapies require continued, regular dosing of medication. A treatment approach consisting of short, infrequent oral treatment cycles may help lower the treatment burden for patients,” said Thomas Leist, M.D., PhD, Director, Comprehensive Multiple Sclerosis Center at Jefferson University Hospitals. “Based on additional clinical research in recent years, we know more about the treatment course, safety, and impact of cladribine tablets across several key measures of MS, and hope it will be made available to the U.S. MS community.”