Approval for MS Pill: Novartis on Heels of Merck Serono

Or, to put it another way: Merck Serono remains just ahead of Novartis in the race for approval of the first oral MS drug.

Yesterday the former company announced its NDA submission for the fast-track approval of oral cladribine, an anticancer drug, in the United States. Use of the agent in relapsing-remitting MS is supported by results from the publicly presented CLARITY study.

But Novartis isn't too far behind.

Also yesterday, Novartis announced that its investigational drug, fingolimod (or FTY720), significantly reduced the relapse rate and disability progression in a 2-year, double-blind, phase 3 study of patients with relapsing-remitting MS. Although the data have evidently not been presented at a public scientific forum, nor have they been peer reviewed.

In Novartis's so-called FREEDOMS study, 2 dosages of fingolimod, 0.5 and 1.25 mg po daily, were compared with placebo in more the 4000 individuals with RRMS. The primary endpoint was the annual relapse rate. The main secondary endpoint was the reduction of the progression of disability.*

MR data complemented the observed clinical efficacy of the drug, claimed Novartis. Fingolimod was "generally well tolerated," but fewer adverse effects were noted with the lower dosage. Given the comparable efficacies of the 2 dosages, continued clinical development will concentrate on the 0.5-mg treatment, wrote the company.

Novartis also states that it will submit data for the approval of fingolimod 0.5 mg in the United States and Europe at the end of this calendar year. The FREEDOMS data will be supported by results from another phase 3 study, TRANSFORMS, in which fingolimod outperformed IM interferon beta-1a (Avonex; Biogen Idec). Novartis is also conducting the follow-up FREEDOMS II study.

Fingolimod is a sphingosine-1-phospate receptor modulator, which is believed to reduce circulating lymphocyte counts by trapping them within lymph nodes. The agent may also have direct deactivating effects on CNS cells. Cladribine, a purine analog, has an extensive history as an anticancer agent—particularly in the treatment of certain leukemias and lymphomas. 

* Defined by the Expanded Disability Status Scale (EDSS).

CLARITY = Cladribine Tablets Treatment MS Orally; FREEDOMS = FTY740 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis; NDA = new drug application; TRANSFORMS = Trial Assessing Injectable Interferon vs FTY720 Oral in RRMS.