The MS Holy Grail: It's a Horse Race for FDA Submission of Oral Agent

Merck KGaA and its Merck Serono division will submit phase 3 data to the FDA in mid-2009 for the fast-track approval of oral cladribine in patients with relapsing-remitting multiple sclerosis (RRMS). The companies issued a press release on Friday, describing favorable 2-year data from an extension phase of a pivotal phase 3 trial, CLARITY.

In the 2-year, randomized, double-blind international study (N = 1326), the annualized relapse rate (the primary endpoint) with various cladribine regimens was approximately 60% lower than that with placebo (P < .001). Secondary endpoints of the study, including a reduction of MRI lesion activity, relapse-free rates, and disability progression were also significantly lower with cladribine.

Cladribine-specific adverse events included the expected lymphopenia. In addition, 4 cases of cancer—early-stage cervical, melanoma, ovarian, and pancreatic—occurred in RRMS patients who received cladribine, reports today's Bloomberg. Nevertheless, completion rates in the study were very high: 90% of cladribine-treated patients and 87% of placebo-treated patients.

Currently available, FDA-approved disease-modifying medications for RRMS must be administered by injection. These include a subcutaneous formulation of interferon beta for multiple sclerosis, Rebif, which is marketed by Merck Serono. Cladribine, a purine analog, has been marketed as the injectable Leustatin by Ortho-Biotech since 1993 for the treatment of hairy cell leukemia. Nonproprietary formulations are available from Bedford and Abraxis, according to the FDA web site.

Novel oral compounds in phase 3 development for MS include fumerate (Fumaderm or BG-12; Biogen Idec), fingolimod (Novartis), laquinimod (Teva), and teriflunomide (sanofi-aventis).

CLARITY = CLAdribine Tablets Treating MS OrallY.