Commentary
Article
Insights on the Newly Approved Subcutaneous Infusion Therapy for Parkinson Disease
Jonathan Rubin, MD, MBA, chief medical officer at Supernus Pharmaceuticals, talked about the recent approval of the company’s subcutaneous infusion therapy SPN-830 for Parkinson disease.
Jonathan Rubin, MD, MBA
(Credit: Supernus Pharmaceuticals)
Apomorphine is a potent dopamine agonist with affinity for all dopamine receptor subtypes and has been used to treat Parkinson disease (PD) since its approval in 1993. It has remained the only medication with symptomatic efficacy comparable with levodopa for PD. In addition, subcutaneous apomorphine infusion is approved for severe motor fluctuations and has been reimbursed by several healthcare systems globally. Several studies have demonstrated its efficacy in reducing OFF time as well as improving dyskinesias and enabling reductions in oral levodopa doses. However, despite its long clinical history, apomorphine infusion had never been assessed in a randomized controlled trial, which presented a gap in the formal evidence base.
The randomized, placebo-controlled, double-blind TOLEDO study (NCT02006121), published in 2018, aimed to investigate the efficacy and safety of apomorphine subcutaneous infusion in patients with PD.1 This study enrolled patients with PD from 23 European hospitals who had been diagnosed for over 3 years and experienced motor fluctuations not adequately managed by medication. Patients were randomly assigned to receive either 3–8 mg/h of apomorphine or a placebo saline infusion for 16 hours daily over 12 weeks. The first 4 weeks allowed dose adjustments based on efficacy and tolerability, followed by an eight-week maintenance phase. The primary end point was the change in daily OFF time, assessed using patient diaries. Safety was assessed in all participants who received at least 1 dose, and both patients and investigators remained blinded to treatment assignments.
Recently, the FDA approved SPN-830 (Onapgo; Supernus Pharmaceuticals), a subcutaneous apomorphine infusion device, for motor fluctuations in adults with advanced PD based on findings from the TOLEDO study.2 In a recent interview with NeurologyLive®, Jonathan Rubin, MD, MBA, chief medical officer and senior vice president of Research & Development at Supernus Pharmaceuticals, discussed the potential impact of SPN-830 on PD management. He highlighted how this approach could offer a long-term treatment option for patients experiencing motor fluctuations. Rubin also emphasized the importance of clinician assessment in determining whether SPN-830 is suitable for individual patients. Additionally, he underscored the role of a support program for SPN-830 in improving patient adherence, ensuring continuous education, and optimizing treatment outcomes.
NeurologyLive: What was your immediate reaction to the approval?
Jonathan Rubin, MD, MBA: We have a long history of collaboration with the PD community leading up to this approval, so the mission to get Onapgo into the hands of patients has become personal for many of us. When we heard that the FDA approved Onapgo, we were incredibly excited that we could deliver on our promise to patients and uphold our company’s mission to improve the lives of people living with diseases of the central nervous system.
How do you anticipate the introduction of this therapy will change the landscape of care in PD? Do you foresee any added positive downstream effects on care or drug development?
There is no known cure for PD, and the community needs additional treatments to help manage symptoms as Parkinson progresses. As a subcutaneous infusion device, Onapgo is an important intermediate option that can allow patients to manage their motor fluctuations without resorting to invasive surgical procedures.
It’s also important to understand that care for PD extends beyond treatment. We’re proud to have robust a support program with the Onapgo Circle of Care™, which surrounds patients and care partners with experts who provide comprehensive and continuous support from the moment Onapgo is prescribed.
Could you offer an overview of the supported data to this point on the treatment?
The approval is based on results from the TOLEDO phase 3 study. Onapgo significantly reduced the amount of daily OFF time among Onapgo-treated patients by 2.6 hours, compared with the placebo group with 0.9 hours. Simultaneously, Onapgo-treated patients experienced a 2.8-hour increase in daily GOOD ON time, compared with the placebo group with 1.1 hours. Numerically greater improvements in daily OFF time and daily GOOD ON time were seen as early as week 1 and were maintained throughout all measured timepoints. Additionally, Onapgo-treated patients more frequently reported improvement in their state of general health compared with placebo-treated patients (PGIC, 79% vs. 24%; P <.0001).
Are there any considerations that physicians should take when prescribing this therapy? Are there any adverse events of interest or monitoring?
It’s important for physicians to review Onapgo’s prescribing information to determine if the product is appropriate for their patients. The most common adverse events (at least 10% incidence) were infusion-site nodule, nausea, somnolence, infusion-site erythema, dyskinesia, headache, and insomnia.
Is there anything else you think is important for the PD clinical community to know about this treatment?
As PD progresses, patients report alternating states between ON when their medication is working, and OFF when it’s not managing their symptoms well. These on-again, off-again changes are disruptive and can happen at any time. Continuous treatment options like Onapgo that can offer consistent daily control of OFF time can help to make days with Parkinson more predictable. Supernus will make Onapgo available in the second quarter of 2025 with a support team of experts, including a robust nurse education program, and access support at launch.
Transcript edited for clarity.
