FDA Rejects Oral Cladribine for MS

Delivering a minor shock, the FDA issued a complete response letter to Merck KGaA* today, indicating that the agency will not approve cladribine tablets for the treatment of relapsing-remitting multiple sclerosis (RRMS). While the FDA concluded that there is "substantial evidence" of the drug's efficacy from the CLARITY study (the results of which were published in the NEJM about a year ago), the agency was apparently underwhelmed by the volume of safety data to justify a favorable risk-benefit profile for the drug.

In response, "Merck intends to request an end-of-review meeting with the FDA to clarify next steps and to identify whether data from completed and ongoing clinical study can address the Agency's questions." The struggle for cladribine approval may not be completely over, implies the company in a press release, as "top-line" results from the extension phase of the CLARITY trial, the ORACLE MS study, and the ONWARD study are expected during the second half of this calendar year or the first half of 2012.** Both CLARITY and ORACLE MS were/are 2-year, placebo-controlled, phase 3 trials of monotherapy. ONWARD is a phase 2 study of oral cladribine as add-on therapy to interferon beta.

In Australia and Russia, oral cladribine is approved for the treatment of RRMS under the comic-book-sounding trade name, Movectro.

Presently the only disease-modifying pill option for US patients with RRMS is Novartis's astronomically priced Gilenya (fingolimod)—which was, at one time, in a nail-biting approval horse race with oral cladribine.

CLARITY = Cladribine Tablets Treatment MS Orally; ORACLE MS = Oral Cladribine in Early MS; ONWARD = Oral Cladribine Added on to Interferon Beta-1a in Patients With Active Relapsing Disease.

* The US subsidiary of which is EMD Serono.

** Although clinicaltrials.gov gives an estimated study completion date (primary outcome) of October 2013 for ONWARD.