Within our Neurodegenerative Diseases therapeutic area, we are conducting research to discover new therapeutic options for multiple sclerosis (MS) and Parkinson’s disease – two indications with high unmet medical needs. In REFLEX, a two-year Phase III study involving more than 500 patients, we investigated whether patients with clinically isolated syndrome (CIS) at risk of developing MS could benefit from treatment with the serum-free formulation of Rebif®. Study participants with this clinical picture have so far experienced a single MS-like episode, such as optical or sensory disturbances, and have characteristic MRI lesions, putting them at high risk of developing clinically definite multiple sclerosis. At this early stage, these patients have not yet been given a clinically definite diagnosis, yet they are at risk of developing MS. The trial, which was completed in October, met its primary endpoint by demonstrating that Rebif® significantly delays conversion to clinically definite MS in these patients. A three-year double-blind extension of the REFLEX study, called REFLEXION, is currently ongoing in order to provide long-term follow-up data.
Progress made with the further development of cladribine tablets
With cladribine tablets, the Merck Serono division is developing a drug for the oral, short-course treatment of relapsing-remitting multiple sclerosis. In 2010, we received regulatory approvals in Russia and Australia. Our regulatory application received a negative opinion in the European Union. It is currently under review in the United States. The clinical development program for cladribine tablets is designed to evaluate the potential therapeutic effects of cladribine tablets in various stages of the disease. Following the successful completion of the CLARITY study, a two-year extension with around 800 patients is currently underway to provide data on the long-term safety and efficacy of cladribine tablets as a monotherapy in relapsing-remitting MS. The two-year Phase III ORACLE-MS study is investigating cladribine tablets as a monotherapy in patients with clinically isolated syndrome. In November, we completed the recruitment of more than 600 study participants. In the Phase II ONWARD study, we are evaluating the safety and tolerability of adding cladribine tablets to established treatment with interferon beta.
Long-term study completed with safinamide in late-stage Parkinson’s disease
Together with our partner Newron, we are developing safinamide as an oral adjunctive therapy for patients with various stages of Parkinson’s disease, which affects an estimated three million people in industrialized countries. In 2009, we had successfully completed the first Phase III clinical trial of safinamide administered as an add-on therapy to levodopa standard treatment in patients with advanced Parkinson’s disease (Study 016). Motor function and the ability to perform daily activities improved significantly in patients treated with safinamide compared to placebo. An 18-month extension study (Study 018) was intended to provide data on the long-term efficacy and safety of safinamide in this indication. We announced the results of this long-term study in November 2010. The primary efficacy endpoint measuring dyskinesia after 24 months of treatment was not met. We therefore reassessed the sales potential of safinamide and recorded an impairment. By contrast, the results of the analysis of the main secondary endpoint were consistent with the effect on motor function observed in Study 016. The data from Study 018 also confirm the safety profile of safinamide. With SETTLE, a further Phase III clinical trial is underway in this indication. In the MOTION study, a Phase III clinical trial, we are evaluating safinamide as an add-on therapy to a dopamine agonist in early Parkinson’s disease.