FDA Approves Apomorphine Hydrochloride to Treat Motor Fluctuations in Advanced Parkinson Disease

Key Takeaways

Apomorphine hydrochloride (Onapgo) is the first subcutaneous infusion device approved for advanced Parkinson's disease motor fluctuations.
The phase 3 TOLEDO study showed a 2.6-hour reduction in "off" time with apomorphine versus 0.9 hours with placebo.
The device offers a non-invasive treatment alternative for patients unresponsive to current therapies, such as levodopa.
This approval provides a new option to improve quality of life for patients with advanced Parkinson's disease.

The approval marks the first subcutaneous infusion device approved for the treatment of Parkinson disease, providing a new option for patients with serious disease who are unresponsive to other therapies.

The FDA has granted regulatory approval to apomorphine hydrochloride (Onapgo; Supernus Pharmaceuticals) injection, becoming the first and only subcutaneous apomorphine infusion device for the treatment of motor fluctuations in adult patients with advanced Parkinson disease (PD), according to a news release from Supernus Pharmaceuticals.¹

Trembling hand holding glass with alcohol drink

Parkinson disease can cause motor fluctuations, making it difficult to complete everyday tasks. | Image Credit: © Alessandro Grandini | stock.adobe.com

The approval is based on positive clinical trial results from the phase 3 TOLEDO study (NCT02006121), which evaluated the efficacy and safety of apomorphine hydrochloride. The primary efficacy end point of mean change in total daily off time—the time where symptom benefit ceases and motor symptoms return—was assessed; patients treated with apomorphine hydrochloride experienced a 2.6-hour reduction in off time, compared with 0.9 hours in placebo.²

“Today’s approval of [apomorphine hydrochloride] means patients in the US who are not responding well to their current treatment regimen, including levodopa [Sinemet; AbbVie], 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,” Rajesh Pahwa, MD, clinical trial investigator, said in the news release.¹

About the Trial

Trial Name: Clinical Trial of Apomorphine Subcutaneous Infusion in Patients With Advanced Parkinson's Disease (TOLEDO)

ClinicalTrials.gov ID: NCT02006121

Sponsor: Britannia Pharmaceuticals Ltd.

Completion Date: June 8, 2017

In addition to positive reductions in daily off time, patients experienced a significant increase in daily good on time, defined as time without troublesome dyskinesia (2.8 hours for treated patients, compared with 1.1 hours for the placebo group; P = .0188). In an important observation, these improvements were reported as early as week 1 and maintained throughout all measured end points, according to the investigators.¹

Apomorphine hydrochloride’s ease of use—it is a wearable, subcutaneous infusion device that provides sustained treatment throughout the day—could allow for better patient control of PD symptoms and improved treatment adherence. Motor fluctuations occur at greater frequency in patients with advanced PD, presenting a major burden across daily life and during routine activities in both the short- and long-term.

The open-label extension of TOLEDO that examined long-term outcomes with apomorphine hydrochloride, which went up until 64 weeks, found sustained reductions in OFF time and improvements in GOOD ON time for patients treated with apomorphine hydrochloride. Furthermore, there were no unexpected safety signals observed during treatment, and treatment with apomorphine hydrochloride led to significant reductions in oral PD medication use.³

“As the motor symptoms of PD 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 in the news release. “For many, continuous treatment options like [apomorphine hydrochloride] can help to make days with Parkinson’s more predictable.”¹

REFERENCES

1. Supernus Pharmaceuticals. Supernus announces FDA approval of ONAPGO (apomorphine hydrochloride) for Parkinson’s disease. News Release. Released February 4, 2025. Accessed February 4, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-announces-fda-approval-onapgotm-apomorphine

2. ClinicalTrials.gov. Clinical trial of apomorphine subcutaneous infusion in patients with advanced Parkinson’s disease (TOLEDO). National Library of Medicine. Last Updated July 8, 2019. Accessed February 4, 2025. https://clinicaltrials.gov/study/NCT02006121

3. Katzenschlager R, Poewe W, Rascol O, et al. Long-term safety and efficacy of apomorphine infusion in Parkinson’s disease patients with persistent motor fluctuations: Results of the open-label phase of the TOLEDO study. Parkinsonism & Related Disorders. 2021;83:79-85. doi:10.1016/j.parkreldis.2020.12.024