FDA rejects Oral Cladribine

From Medscape-- not sure how to take this, given its checkered history, but at least Russians and Aussies can get it:


FDA Rejects Oral Cladribine for Multiple Sclerosis
Allison Gandey

March 2, 2011 — The US Food and Drug Administration (FDA) says it won't approve oral cladribine (Movectro, Merck Serono) for multiple sclerosis (MS) without more safety information. Merck announced today it received a complete response letter from the agency calling for additional analyses or new studies.

The company says it plans to request an end-of-review meeting with the FDA to clarify next steps and to identify whether data from completed and ongoing clinical studies can address the questions.

The FDA decision is the latest in a long line of disappointment for the new drug in the race for first oral agent for MS. Cladribine was initially granted fast-track status by the FDA in 2006, but the agency refused to file the company's new drug application in 2009 amid speculation about tabulation errors and potential safety concerns.

Oral fingolimod (Gilenya, Novartis) beat cladribine to market for relapsing-remitting MS. Other oral MS treatments in development include laquinimod (Teva), teriflunomide (sanofi-aventis), and BG-12 (Biogen).

Cladribine was recently approved in Russia and Australia but received a negative opinion from European regulators in September that was reiterated in January.

Increase in Cancer Cases
The European Medicines Agency said it was concerned about the increase in cancer cases seen in clinical trials with treatment. Regulators also complained the benefits and most appropriate dosage had not been well established.

The company says it will remain committed to completing the ongoing clinical trials of cladribine. These trials, already fully enrolled, will provide additional information on efficacy and safety.

Top-line results from the CLARITY (CLAdRIbine Tablets Treating MS OrallY) extension study and ORACLE MS (Oral Cladribine in Early MS) study are expected by the end of 2011. Top-line results from the ONWARD (Oral Cladribine Added ON To Rebif [interferon beta-1a] New Formulation in Patients With Active Relapsing Disease) study are anticipated in the first half of 2012.

"We look forward to working with the FDA to address the safety issues in its letter," Fereydoun Firouz, president and chief executive officer of EMD Serono, said in a statement.

"We will continue to move toward identifying a path that provides patients and physicians the opportunity to have access to cladribine tablets in the treatment of MS."