Our development projects in Neurodegenerative Diseases are focused on innovative therapeutic options for multiple sclerosis (MS) and Parkinson’s disease – two areas with high unmet medical needs. The Merck Serono division wants to expand the range of approved indications for the successful MS treatment Rebif® based on the outcome of clinical trials. One of the aims is to enable more patients in the early stages of the disease to benefit from treatment with Rebif®. In September, we completed the enrollment of more than 500 patients for the REFLEX trial, one of the most important studies on the further development of Rebif®. This 24-month Phase III registration study will examine the efficacy of the new formulation of Rebif® in clinically isolated syndrome. In this new indication, the study participants have so far only experienced MS-like attacks, but have not yet been diagnosed with clinically defined MS. The aim of the study is to investigate the therapeutic value of Rebif® prior to the outbreak of MS in these patients.
Initial results of the ongoing Phase IIb IMPROVE study after 16 weeks of treatment show that the primary endpoint has been met, confirming the therapeutic effect of the new formulation of Rebif® in MS patients. The number of active lesions in the brain as measured by magnetic resonance imaging was significantly lower than in patients treated with the new formulation of Rebif® compared with those receiving placebo in the control group.
Oral MS treatment – a new therapeutic option in development
With cladribine tablets, Merck Serono is developing a drug that – once approved – would represent the first therapeutic option for oral treatment of relapsing MS. Patients would only need to take this proprietary oral formulation of a nucleoside analogue a few times a year for a period of four to five days in a single daily dose, making treatment considerably more comfortable and improving the prospects for compliance. The U.S. Food and Drug Administration has given cladribine tablets fast-track designation. The safety and efficacy of cladribine tablets as an MS monotherapy in two dosage strengths were tested in a two-year Phase III registration study called CLARITY. This study, which involved more than 1,300 patients, was completed at the end of 2008. According to the results of the trial, which met the primary endpoint, the relapse rate was significantly reduced. Patients who received a lower total dose experienced a 58% relative reduction in annualized relapse rates versus placebo while patients who received a higher total dose experienced a 55% reduction. We initiated ORACLE-MS, a further Phase III trial, at the end of September. It will evaluate the efficacy of cladribine in preventing conversion to definite multiple sclerosis in patients at risk of developing multiple sclerosis. The Phase II study ONWARD, which is currently underway, is examining the safety and efficacy of cladribine as an add-on to treatment to interferon beta, for example the new formulation of Rebif®.
Merck Serono is also developing atacicept for the treatment of multiple sclerosis. In April 2008, we initiated a Phase II study to evaluate the efficacy of atacicept in reducing central nervous system inflammation in patients with relapsing MS. In June, an exploratory Phase II trial was started to evaluate the efficacy of atacicept in optic neuritis. Inflammation of the optic nerve is a condition often experienced as an early clinical manifestation by patients with multiple sclerosis.
Safinamide – a potential add-on treatment in Parkinson’s disease
Safinamide, an orally administered add-on treatment with a novel mechanism of action, is also in late-stage clinical trials. Together with the Italian pharmaceutical company Newron, we are developing safinamide for Parkinson’s disease. A Phase III study to evaluate safinamide as an add-on treatment to levodopa in patients with advanced Parkinson’s met its primary endpoint. The motor functioning of patients with advanced Parkinson’s disease improved significantly. The “ON” times during which motor function reaches its highest levels were extended by 1.3 hours. In a Phase III study called MOTION, we are evaluating safinamide as an add-on therapy to dopamine agonist in early-stage disease.