New Drug Extends Levodopa’s Benefits in Moderate and Advanced Parkinson’s Disease

- Aug 06 2014

A drug not yet approved in the US called safinamide increases “on” time and helps improve other Parkinson’s disease (PD) symptoms when taken as an add-on to levodopa therapy, according to the results of a phase III clinical trial reported in the July 10 online edition of Movement Disorders. 

Levodopa, usually taken as carbidopa-levodopa (Sinemet®), is the most effective medication for the movement symptoms of Parkinson’s disease.  However, after taking this drug for several years, most people experience fluctuations in its effectiveness. During the “on” periods when the drug is working, many people experience involuntary movements (dyskinesias) as a side effect.  During the “off” times, when the drug wears off before the next scheduled dose, people experience a return of PD symptoms.

Safinamide is a drug developed with the goal of extending “on” periods in people taking levodopa without worsening their dyskinesias.  Researchers led by Rupam Borgohain, D.M., at Nizam’s Institute of Medical Sciences in Hyderabad, India, recruited study participants at 52 medical centers in India, Romania and Italy to test the drug’s safety and effectiveness.  The researchers conducted the most rigorous type of clinical trial: randomized, double-blind and placebo-controlled.  The primary end point of the study (the measurement indicating whether a treatment is effective) was improvement in dyskinesia as measured by a rating scale, and a second was a change in “on” time without troublesome dyskinesia.

For six months, 669 people with mid- to late-stage PD and who experienced ”on” and “off” periods, followed one of three treatment options: 50 mg/day of safinamide, 100 mg/day of safinamide or a placebo pill.  All three of the treatment groups continued their levodopa and other PD medications.  Of these study participants, 440 continued the trial for an additional 18 months. 

Results

• There was no significant difference between the groups in regards to the primary end point – change in the dyskinesia rating scale.
• People who took safinamide, at both the 50 mg/day and the 100 mg/day doses, experienced 45 minutes more “on” time without troublesome dyskinesias compared with people who took placebo pills.
• At both doses, safinamide was safe and well-tolerated for the two-year study period.
• Dyskinesias improved in participants who had moderate to severe dyskinesia at the beginning of the study, and who took 100 mg/day of safinamide.
• People who took 100 mg/day of safinamide also showed improvement in PD motor symptoms, ability to do daily activities, symptoms of depression and quality of life.
• People who experience improvement in PD movement symptoms while taking 100 mg/day of safinamide, still demonstrated improvement during the 18-month extension study.

What Does It Mean?

It is challenging to treat moderate and advanced Parkinson’s disease.  Although carbidopa-levodopa often works well to ease symptoms, many people taking the drug experience debilitating fluctations and dyskinesia.  Doctors already prescribe several medications to be taken alongside levodopa to lessen side effects and extend its benefits.  This study, the first long-term investigation into safinamide’s effects, provides encouraging evidence that the drug may provide benefits when used in combination with levodopa or other PD medications.   

Strengths of the clinical trial include that, as in a real-life situation, participants continued their usual regimens of PD medications, and also that safinamide did not worsen existing side effects or cause new ones.  The drug’s manufacturer, Newron, submitted a new drug application — an application for approval to distribute safinamide in the United States—to the US Food and Drug Administration in May 2014.  Their application included requests that the drug be approved for use not only as an add-on to levodopa but also for people with early-stage PD who take dopamine agonists (for example, pramipexole or ropinirole). Previous studies have indicated safinamide can help movement symptoms in these cases.  While the improvements in symptoms seen with the use of safinamide are modest, it is likely that, if approved, safinamide could become another useful tool in the management of Parkinson’s disease.

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