In the Neurodegenerative Diseases therapeutic area, Merck Serono is conducting research to develop innovative drugs for multiple sclerosis (MS) and Parkinson’s disease, where high medical needs for new therapeutic options exist. The division is investing steadily in the further development of its successful multiple sclerosis product Rebif®. The most recent example was the approval and market launch of a new formulation in Europe. Based on clinical trials, the range of approved indications is to be expanded so that more patients, for example those in the early stages of the disease, can benefit from treatment with Rebif®. REFLEX is among the most important clinical trials on the further development of Rebif® currently being conducted by Merck Serono. REFLEX is a 24-month Phase III registration study of 480 patients that is examining the efficacy of the new formulation of Rebif® in a new indication, namely clinically isolated syndrome. The study participants are patients at risk of developing MS and in whom so far only an MS-like attack has occurred but who have not yet been diagnosed with clinically definite MS. The purpose of the study is to find out whether these patients could benefit from early treatment with Rebif®. Patient recruitment is currently in progress.
The 40-week Phase IIIb IMPROVE study involving 150 MS patients is examining the efficacy of the new formulation of Rebif® versus placebo. The assessment will be based on the measurement via magnetic resonance imaging of active lesions in the brain.
Oral MS treatment would improve therapeutic success
With cladribine tablets, Merck Serono is developing a drug that – once approved – would represent the first therapeutic option for oral treatment of relapsing forms of multiple sclerosis. This is a proprietary oral formulation of a nucleoside analogue which patients would only need to take a few times a year for a period of five days in a single daily dose. It would make treatment considerably more comfortable and improve the prospects for compliance. The safety and efficacy of cladribine tablets as a monotherapy in multiple sclerosis are currently being tested in more than 1,300 patients enrolled in a two-year Phase III study called CLARITY. Patient enrollment was completed in January 2007. The U.S. Food and Drug Administration has given cladribine tablets fast track designation as a potential monotherapy for patients with relapsing forms of multiple sclerosis. ONWARD, a Phase II study involving 260 MS patients that also started in January, is examining the safety, tolerability and efficacy of cladribine tablets as an add-on to treatment with interferon beta-1a – for example the new formulation of Rebif®.
New mechanism of action in the treatment of Parkinson’s disease
Safinamide, an orally administered alpha-aminoamide derivative with a novel mechanism of action, is currently in late-stage clinical trials. Together with Newron, Merck Serono is developing safinamide as an add-on treatment to existing treatments, such as stable doses of single dopamine agonists or levodopa, for early-stage as well as mid- to late-stage Parkinson’s disease. The results of a six-month Phase III trial with safinamide as an add-on treatment to dopamine agonist therapy in patients with early-stage Parkinson’s disease were presented at the 59th Annual Meeting of the American Academy of Neurology in May. The data showed that the addition of safinamide at a dose of 50 to 100 mg led to an improvement in motor symptoms. In August, Merck Serono announced the results of a twelve-month extension study of this six-month trial. The primary efficacy endpoint, time to intervention, did not reach statistical significance when data from both safinamide dose groups were pooled. However, a post-hoc analysis of the data showed that the addition of safinamide at a dose of 50 to 100 mg once daily to dopamine agonist therapy delays the time to intervention for therapeutic adjustment. The MOTION trial, a Phase III study that was initiated at the end of 2007, will evaluate safinamide in this dose range as an add-on therapy to a dopamine agonist in early Parkinson’s disease.
Merck Serono is developing atacicept together with ZymoGenetics for the treatment of multiple sclerosis. Phase II studies, which will evaluate the anti-inflammatory effect of atacicept in multiple sclerosis, are expected to begin in 2008.
