SPN-830, now Onapgo, approved for advanced Parkinson’s disease
Therapy is first subcutaneous apomorphine infusion device for indication
The U.S. Food and Drug Administration (FDA) has approved Onapgo (apomorphine hydrochloride) for the continuous treatment of motor fluctuations in adults with advanced Parkinson’s disease, making it the first subcutaneous, or under-the-skin, apomorphine infusion device approved for this indication.
The application from Supernus Pharmaceuticals was the developer’s fourth attempt to have the therapy cleared by the FDA since acquiring it from US WorldMeds in 2020. FDA requests for more information regarding quality and manufacturing or device performance sidelined earlier applications.
According to Supernus, Onapgo will be available in the second quarter of 2025, and the company will provide a support system at launch, including a robust nurse education program and resources to facilitate access to the therapy.
“Onapgo represents a novel approach for adults with Parkinson’s disease who are experiencing motor fluctuations,” Jack Khattar, president and CEO of Supernus Pharmaceuticals, said in a press release.
In Parkinson’s, the nerve cells that produce the signaling molecule dopamine degenerate. The standard treatment is levodopa, a dopamine precursor molecule that temporarily increases dopamine levels with each dose. However, the effects of levodopa or related dopamine-boosting treatments can wear off between doses, leading to periods of worsening motor symptoms known as off episodes or motor fluctuations.
Apomorphine is a molecule that mimics dopamine’s activity in the brain. Supernus markets a formulation of it called Apokyn that’s approved in the U.S. as an on-demand treatment for easing off episodes. Apokyn is given subcutaneously via an injection pen.
What is SPN-830, now Onapgo?
Previously called SPN-830, Onapgo consists of a portable electronic pump that continuously delivers apomorphine via a subcutaneous infusion over 14-18 hours a day. This is intended to provide a steadier supply for better symptom control while also being less invasive, that is, requiring fewer injections, than other formulations.
“As Parkinson’s disease progresses, levodopa treatment often becomes less effective at delivering consistent motor control in part due to [gastrointestinal dysfunction], variable absorption of oral medication, and the resulting pulsatile stimulation of dopamine pathways in the brain,” said Stuart Isaacson, MD, Director of Parkinson’s Disease and Movement Disorders Center of Boca Raton, Florida, and a clinical trial investigator for Onapgo. “With Onapgo, the continuous infusion of apomorphine directly stimulates … dopamine receptors with no metabolic conversion needed. In addition, the subcutaneous delivery of apomorphine bypasses the [gastrointestinal] tract and enters the brain, which can allow for more predictable symptom improvement.”
Onapgo’s approval was based on data from an European placebo-controlled Phase 3 study (NCT02006121) called TOLEDO that indicated continuous apomorphine infusions reduced off time and increased on time, when symptoms are adequately controlled, among patients who were experiencing multiple hours of daily off time with levodopa-based treatment regimens.
“As the motor symptoms of Parkinson’s disease worsen over time, patients report alternating states between on, when their medication is working, and off, when it’s not working optimally,” Andrea Merriam, CEO of the Parkinson & Movement Disorder Alliance, said. “These on-again off-again changes are disruptive and can happen at any time, which is why consistent daily control of off time is key to improving how patients feel and move. For many, continuous treatment options like Onapgo can help to make days with Parkinson’s more predictable.”
Long road to Onapgo’s approval
Despite these demonstrated benefits, Supernus has faced challenges in getting the therapy approved by the FDA.
The company first applied for SPN-830’s approval in 2020, but regulators said the application lacked sufficient data for review. A resubmitted application in 2021 was rejected due to concerns about labeling, device performance, quality and manufacturing, and risk analyses. A third application in 2023 was again rejected because the FDA sought more information about the product’s quality and the infusion device.
A similar therapy has been available in Europe since the 1990s for severe motor fluctuations.
“Continuous subcutaneous apomorphine infusion already has a proven and established 30-year history in Europe, where it has helped deliver more consistent control of motor fluctuations for thousands of patients,” said Rajesh Pahwa, MD, Laverne and Joyce Rider Professor of Neurology at the University of Kansas School of Medicine, director of the Movement Disorder Program at The University of Kansas Health System, and a clinical trial investigator for Onapgo. “Today’s approval of Onapgo means patients in the U.S. who are not responding well to their current treatment regimen, including levodopa, will now have the option of using a small and lightweight wearable device to deliver a continuous infusion without the need for an invasive surgical procedure.”
The most common side effects of Onapgo include infusion site reactions, nausea, somnolence, headache, insomnia, and dyskinesia, or uncontrolled movements.
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