The open-label INFUS-ON study was the first to use SPN-830 in the U.S., and results from the trial showed that the apomorphine infusion pump reduced ‘off’ time, when symptoms are not being adequately controlled, by an average of about three hours a day. This was reported by Stuart Isaacson, MD, a neurologist at the Parkinson’s Disease and Movement Disorder Center of Boca Raton in Florida, at the American Academy of Neurology (AAN) annual meeting.
Parkinson’s is caused by the death and dysfunction of cells in the brain responsible for making the signaling molecule dopamine. Standard treatment includes levodopa and its derivatives, which give these cells more material to make dopamine. While levodopa can manage symptoms, many patients have off episodes with long-term treatment where symptoms are not adequately controlled between doses. Dyskinesia, or uncontrolled movements, can also occur over time.
Apomorphine (sold as Apokyn, among others) mimics dopamine’s activity in the brain. It’s approved in the U.S. for managing off episodes and the approved version of it is administered subcutaneously (under the skin). SPN-830 delivers the therapy in a continuous infusion, making it more convenient and with fewer injection sites. It’s approved in much of Europe, Asia, and Australia.
The Phase 3 INFUS-ON study enrolled adults with advanced Parkinson’s who were having at least three hours of off time a day, despite optimized treatment that included levodopa and at least one other Parkinson’s therapy. Participants initially entered a titration period, where the SPN-830 dosage was adjusted to optimize controlling symptoms with minimal side effects. This typically took about a month. Once the optimized dose was identified, participants entered a maintenance period for about a year. The average dose of apomorphine during the maintenance phase was 45.2 mg a day, with most patients receiving an infusion rate between 3 and 5 mg per hour.
Results showed that, by 12 weeks in the maintenance phase, daily off time had decreased by about three hours on average. Consistently, daily “good on” time, when symptoms are controlled without troublesome dyskinesia — increased by about three hours a day on average. By week 12, 62.1% saw a reduction in off time of at least two hours a day. Around 90% of patients reported their overall health status had improved since starting SPN-830 and just over two-thirds (65%) said they were “much improved” or “very much improved” at week 12.
The most common side effects associated with SPN-830 included nodules or redness at the infusion site, nausea, dyskinesia, and sleepiness. These generally were more common during the titration part and were reported less often once participants were on an optimized long-term dose. The most common reason for stopping participating was side effects related to SPN-830, especially reactions at the infusion site. In total, 17% in the titration phase and 19% of patients at the maintenance phase discontinued due to side effects. While infusion site reactions occurred in nearly four of every five patients, none were judged to be severe.
These findings suggest that SPN-830 may be an effective treatment for reducing ‘off’ time in Parkinson’s patients. Supernus Pharmaceuticals is seeking SPN-830’s approval with the U.S. Food and Drug Administration (FDA), and data from the two studies “hopefully will lead to this therapy finally becoming available in the [U.S.].” 1