· Side effects/ECG changes/vital sign abnormalities were reported with similar frequency across treatment groups
· For the primary efficacy endpoint (time to intervention), although a delay of 93 days in median time to intervention was observed, statistical significance was not reached, when data from all safinamide dose groups were pooled; the lack of a significant effect might be explained by the lack of response with the high dose group (150-200 mg) as seen in the analysis of the first six months
· A post-hoc analysis (as described below) showed that the addition of safinamide at a dose of 50 to 100 mg once daily to dopamine agonist therapy significantly reduced the number of patients who experienced an intervention, maintained improvement in motor symptoms and improved quality of life compared with dopamine agonist monotherapy
Milan, Italy – August 22, 2007 - Newron Pharmaceuticals S.p.A., (“Newron”, SWX: NWRN), a research and development company focused on novel CNS and pain therapies, and its partner Merck Serono, a division of Merck KGaA, announced today preliminary results of a 12-month extension study of a 6-month Phase III trial of safinamide as an add-on treatment to dopamine agonist therapy in patients with early stage Parkinson’s disease. Results from the initial 6-month trial were presented in May at the American Academy of Neurology 59th Annual Meeting.
“These 18-month data suggest that, at a dose of 50 to 100 mg once daily, safinamide may delay the time to intervention for therapeutic adjustment and provide sustained improvement of Parkinson’s disease symptoms when added to dopamine agonist therapy,” said Professor Anthony Schapira, chairman of the University Department of Clinical Neuroscience, Royal Free and University College London Medical School, and an investigator of the study. “Additional Phase III studies are planned to further assess the efficacy of this dose of safinamide. Because Parkinson’s disease is a neurodegenerative disease, if approved, safinamide could meet an important unmet medical need.”
The 18-month, Phase III, randomized, double blind, placebo-controlled, international trial enrolled patients with early stage Parkinson’s disease (less than 5 years of disease) treated with a stable dose of a single dopamine agonist. Patients were randomized to one of the three arms of the study to receive either safinamide at a dose of 50 to 100 mg once daily, safinamide at a dose of 150 to 200 mg once daily, or matching placebo tablets, as an add-on treatment to dopamine agonist therapy. Patients who entered the initial 6-month Phase III trial were given the opportunity to continue the study for an additional 12 months, receive other treatments for Parkinson’s disease, or to discontinue therapy. Of the 270 patients originally enrolled in the trial, 227 entered the 12-month extension; 187 patients completed the 12-month extension period. The main reasons for discontinuation were side effects (safinamide 50-100 mg: 3.8%; safinamide 150-200 mg: 1.4%; placebo: 3.9%), lack of efficacy (safinamide 50-100 mg: 2.5%; safinamide 150-200 mg: 5.8%; placebo: 6.4%) and withdrawal of consent (safinamide 50-100 mg: 10.0%; safinamide 150-200 mg: 4.3%; placebo: 6.4%).
The primary efficacy endpoint of the 18-month trial was time from baseline to intervention. Intervention was defined by the onset of one of the following events: increase in dose of dopamine agonist; or addition of another dopamine agonist, levodopa or another Parkinson’s disease therapy; or discontinuation due to lack of efficacy. Analysis of the primary efficacy measure indicated that safinamide treatment (data from all doses pooled) delayed the onset of the above events by 93 days (3 months) as measured by the median time to event (559 days versus 466 days; p=0.334, not statistically significant). As the risk of experiencing an intervention (hazard ratio) was not constant over time, a post-hoc analysis permitting an evaluation of events beyond the initial phase (>240 days) was performed. This indicated that patients receiving safinamide at a dose of 50 to 100 mg once daily experienced a significantly lower rate of events compared with patients receiving dopamine agonist monotherapy (25% versus 51%; p=0.049).
A post-hoc analysis of the mean change in motor symptoms, as measured by the Unified Parkinson’s Disease Rating Scale Part III Motor Score (UPDRS III)1 (secondary efficacy endpoint) demonstrated that the addition of safinamide at a dose of 50 to 100 mg once daily to a stable dose of a single dopamine agonist resulted in a statistically significant improvement in motor symptoms over the 18-month treatment period (minus 4.7±9.34 versus minus 1.95±7.41; p=0.019). This improvement in motor symptoms was accompanied by a statistically significant improvement in quality of life as measured by the Euro quality of life (EuroQoL)2 scale (tertiary endpoint), both in the pooled dose group (safinamide: 0±1.85, placebo: 0.42±1.69; p=0.0046) and in the individual dose groups versus dopamine agonist monotherapy (safinamide 50-100 mg: 0.03±1.95; safinamide 150-200 mg: minus 0.03±1.73; placebo: 0.42±1.69; p low dose versus placebo =0.017; p high dose versus placebo =0.011).
As observed in the initial 6-month trial, the higher safinamide dose-range of 150 to 200 mg per day did not offer any incremental advantage over placebo over an 18-month period.
Side effects were reported with similar frequency in patients receiving safinamide as an add-on to dopamine agonist therapy and in patients receiving dopamine agonist monotherapy. The most frequent adverse events were back pain (safinamide 50-100 mg: 12.5%; safinamide 150-200 mg: 1.4%; placebo: 6.4%), peripheral edema (safinamide 50-100 mg: 3.8%, safinamide 150-200 mg: 4.3%; placebo: 10.3%), cataract (safinamide 50-100 mg: 5.0%, safinamide 150-200 mg: 10.1%; placebo: 6.4%), scotoma (safinamide 50-100 mg: 8.8%, safinamide 150-200 mg: 2.9%; placebo: 7.7%), and dizziness (safinamide 50-100 mg: 7.5%, safinamide 150-200 mg: 4.3%; placebo: 5.1%).
A Phase III trial evaluating safinamide at the 50 to 100 mg once daily dose-range as add-on to levodopa therapy is ongoing in patients with mid-to-late stage Parkinson’s disease. Additional Phase III trials evaluating this safinamide dose-range either as add-on to dopamine agonist or as add-on to levodopa therapy are expected to be initiated in 2007 in early and mid-to-late stage Parkinson's disease respectively.
Merck Serono has exclusive worldwide rights to develop, manufacture and commercialize safinamide in Parkinson’s disease, Alzheimer’s disease, and other therapeutic applications, as per the agreement signed with Newron.
1 UPDRS
The UPDRS is one of the most widely used rating scales used to follow the course of Parkinson’s disease.
It is made up of 42 items, scored from 0 to 4, to establish individual patients’ mental status, activities of daily living, motor function and complications of therapy.
These are evaluated by interview and clinical observation. Clinicians and researchers alike use the UPDRS and the motor section in particular to follow the progression of a person's Parkinson's disease.
2 EuroQoL
The EuroQoL is a 5-item scale that is used to assess quality of life in patients with Parkinson’s disease. The 5 items rated are mobility, self-care, usual activities (e.g., work or leisure activities), pain/discomfort, and anxiety/depression. Patients are asked to tick one of the three statements under each item, which best describes their current status with regard to their ability to perform a particular activity or the severity of the specific symptom assessed.
Conference Call on August 22nd
Newron management will be available to discuss the results in more detail in a conference call scheduled for today, August 22nd, 4.30 pm CET (and available for playback at www.newron.com) . In order to attend the call, please use the below dial-in information. Please dial in a few minutes before the indicated time to allow a smooth registration process:
Belgium +32 (0) 2 400 1612 France +33 (0) 1 7070 0543 Germany +49 (0) 69 2 2222 0593 Italy +39 02 3600 7818 Sweden +46 (0) 8 5069 2105 Switzerland +41 (0) 91 610 5600 UK +44 (0) 20 7107 0611 US +1 (1) 866 291 4166 All other: +41 (0) 91 610 5600
About Newron Pharmaceuticals
Newron Pharmaceuticals S.p.A. (www.newron.com) is a biopharmaceutical company focused on novel therapies for diseases of the Central Nervous System, particularly Parkinson´s disease (PD), and pain. Newron is undertaking phase III trials with safinamide for the treatment of PD in conjunction with its partner, Merck Serono, which has exclusive worldwide rights to develop, manufacture and commercialize the compound in PD, Alzheimer´s disease, and other therapeutic applications. Safinamide is a unique molecule with a novel dual mechanism of action based on the enhancement of the dopaminergic function (through potent, reversible inhibition of MAO-B, and dopamine uptake) and reduction of glutamatergic activity by inhibiting glutamate release. Recent results of a six-month phase III trial of safinamide in PD as an add-on to dopamine agonist therapy demonstrated its benefit in motor symptoms and activities of daily living, as well as its improvement in cognitive function and good tolerability. Newron is also conducting a phase II programme with ralfinamide for the treatment of neuropathic pain. Phase II data recently reported suggest that ralfinamide is effective in the treatment of this condition. The drug has potential benefit in inflammatory pain, as well. Newron´s clinical pipeline is supported by a portfolio of early-stage proprietary compounds generated by its ion channel drug discovery platform. Newron is headquartered in Bresso, near Milan, Italy. The company is listed at SWX Swiss Exchange, trading symbol NWRN.
For more information, contact: Media Investors and analysts Italy Luca Benatti - CEO Phone: +39 02 6103 4 626
UK/Global media Julia Phillips Financial Dynamics Phone: +44 (0) 20 7269 7187
Switzerland Martin Meier-Pfister The Investor Relations Firm AG Phone: +41 43 244 81 40 Stefan Weber - CFO Phone: +39 02 6103 46 30
