FDA issues CRL to EMD Serono's MS drug

FDA issued a complete response letter to EMD Serono, an affiliate of Merck KGaA, requesting additional information on cladribine (Movectro), a drug intended for the treatment of relapsing-remitting multiple sclerosis (MS).

In the complete response letter, FDA concluded that substantial evidence of cladribine tablets’ effectiveness was provided by the CLAdRIbine Tablets treating MS orally (CLARITY) study. However, FDA has requested the company provide an improved understanding of safety risks and the overall benefit-risk profile either through additional analyses or by additional studies. EMD Serono intends to request an end-of-review meeting with FDA to clarify next steps and to identify whether data from completed and ongoing clinical studies can address the agency’s questions.

This action follows on the heels of Merck Serono Europe informing the European Medicines Agency (EMA) that it was withdrawing its marketing authorization application for oral cladribine, 10-mg tablets, at the end of last month. EMA rejected an application for a license for cladribine in September 2010, reportedly citing concerns about cases of cancer that developed for people involved in trials of the medication. Merck appealed the decision, but it was upheld by the EMA in January.

“This is another example of the FDA process weighing in heavily on patient safety in the review of risk-benefit,” Randy Vogenberg, PhD, principal at the Institute for Integrated Healthcare in Sharon, Mass., and executive director of the Biologic Access & Finance program at The Jefferson School of Population Health in Philadelphia, told Formulary. “Whether the risk of serious adverse events with oral cladribine outweighs the benefit is of particular concern in MS due to past product problems in this category. Avonex [interferon beta-1a], as one example, continues to have serious patient safety issues including death. Merck’s previous issues with Celebrex [celecoxib], which also sensitized the agency to cardiovascular side effects, may also play into the thought process at the Agency.”

“Our commitment to transform the way people living with MS approach their therapy options remains steadfast,” said Fereydoun Firouz, president and CEO of EMD Serono. “We look forward to working with the FDA to address the safety issues in its letter and 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.”

EMD Serono remains committed to completing the ongoing clinical trials with cladribine tablets. These trials, which are fully enrolled, will provide additional information on the efficacy and safety of cladribine tablets in MS.

Cladribine is a small molecule that may interfere with the behavior and the proliferation of certain white blood cells, particularly lymphocytes, which are thought to be involved in the pathological process of MS. Cladribine tablets were approved in Russia in July 2010 and in Australia in September 2010 as a treatment of relapsing-remitting MS and are under regulatory review in other countries.