FDA has requested additional safety and risk-to-benefit data on Merck Serono’s oral multiple sclerosis (MS) therapy, Cladribine, before it can consider approving the drug. The agency’s complete response letter (CRL) states that new safety and risk-to-benefit data will have to be provided on the drug either through additional analyses or by conducting new studies. The firm also points out that in its CRL FDA confirmed the Phase III Clarity study provided substantial evidence for the effectiveness of Cladribine.
Merck Serono says it wants to set up an end-of-review meeting with FDA to find out whether data from completed and ongoing studies will be sufficient to address the issues. Fully enrolled ongoing trials include Clarity Extension and Oracle MS2, which are both expected to yield results by the end of 2011. Data from a third ongoing study, Onwards3, is expected during the first half of 2012.
Cladribine was approved for the treatment of relapsing-remitting MS (RRMS) in Russia during July 2010 and in Australia in September 2010. The drug is trademarked Movectro® in these territories. Regulatory review in other countries is also ongoing.
The clinical development program for Cladribine included four trials to date. Clarity and its extension study were designed to evaluate Cladribine as monotherapy in patients with RRMS, initially over two years, and then for an additional two years through the extension trial.
Oracle MS was a two-year monotherapy study in patients who had experienced a first clinical event suggestive of MS and so were deemed at risk of developing the disease. The Phase II Onward study tested Cladribine as an addition to treatment using interferon beta-1a in patients with active relapsing forms of MS who had experienced breakthrough disease while receiving established interferon beta therapy. The Premier registry was an eight-year observational safety registry of patients participating in Cladribine clinical trials and was designed to support evaluation of the long-term safety of Cladribine.