Merck KGaA disappointed by Parkinson's drug results

By MIke Nagle

- Last updated on GMT

Related tags Dopamine

Newron Pharmaceuticals and its partner Merck KGaA suffered a
disappointment yesterday, when their investigational Parkinson's
disease drug failed a pivotal clinical trial.

In a 12 month extension study of a six month Phase III trial, safinamide did not meet its primary efficacy endpoint. The drug has a novel mechanism of action: like other therapies, it inhibits monoamine oxidase type B (MAO-B) inhibitor - a protein that breaks down dopamine - but it also blocks voltage-dependent Na+ and Ca2+ channels and prevents glutamate release. Parkinson's causes dopamine-producing nerve cells in midbrain to die, leading to muscle rigidity and slowness of movement. This loss of dopamine is normally counteracted through treatment with either dopamine activators or administration of the dopamine precursor levodopa (L-dopa). However, this latter drug becomes less effective over time and the increasing doses needed cause side effects such as uncontrollable movement. Safinamide was designed to protect the neurons and so work in conjunction with dopamine agonists. Although the news will come as a blow for Newron and Merck Serono, a division of Merck KGaA, it doesn't necessarily spell doom and gloom for the drug. The firms believe the drug's lack of efficacy is only an issue at the higher of two doses tested in the trial (150-200 mg compared to 50-100 mg). This result was also observed in the initial six month analysis presented at the 59th American Academy of Neurology meeting in May. "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. The primary endpoint of the trial was 'time to intervention', defined as 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. Although safinamide treatment delayed the onset of the above events by 93 days for both doses, the improvement was not statistically significant. However, a post-hocanalysis showed that the lower dose reduced the number of patients who experienced an intervention (25 per cent versus 51 per cent), maintained improvement in motor symptoms and improved quality of life compared with dopamine agonist monotherapy. "Additional Phase III studies are planned to further assess the efficacy of this dose of safinamide,"​ said Prof. Schapira. MAO-B inhibitors are already commonly used to treat neurodegenerative disorders and depression. The first drug on the market was selegiline (now also in trials as a smoking-cessation therapy), and since then second-generation drugs, such as Lundbeck and Teva's Azilect/Agilect (rasagiline) have been approved.

Related topics Preclinical Research

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