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 2017
FDA Approves Apomorphine for Treatment of Motor Fluctuations in Parkinson Disease
The drug will be made available in the second quarter of 2025.
The FDA approved apomorphine hydrochloride (Onapgo; formerly SPN-830) as the first and only subcutaneous apomorphine infusion device for the treatment of motor fluctuations in adults with advanced Parkinson disease. The drug will be made available in the second quarter of 2025, according to a news release from Supernus Pharmaceuticals Inc.
The approval is based on results from the phase 3 TOLEDO (NCT02006121) study. | Image Credit: airdone | stock.adobe.com
“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,” Rajesh Pahwa, MD, Laverne and Joyce Rider professor of neurology at the University of Kansas School of Medicine and director of the Movement Disorder Program at The University of Kansas Health System, said in a news release.1 “In a clinical trial in Europe, patients treated with Onapgo experienced a significant reduction in daily OFF time and a similar significant increase in GOOD ON time. Today’s approval of Onapgo means patients in the US 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 approval is based on results from the phase 3 TOLEDO (NCT02006121) study, which evaluated the safety and efficacy of apomorphine in 107 patients. As part of the study, investigators evaluated the mean change in time spent “OFF” from baseline to the end of the 12 weeks’ double-blind treatment period. Patients recorded their motor symptoms in half-hour blocks as “OFF,” “ON without dyskinesia,” “ON without troublesome dyskinesia,” or “sleeping” via the Hauser Parkinson’s Disease home diary. Secondary end points included change in time spent “ON without troublesome dyskinesia” and patient global impression of change. Other end points included percentage change of patients with response to therapy and change in oral levodopa and levodopa equivalent dose.Patients included were 30 years or older, diagnosed with idiopathic PD for more than 3 years, had motor fluctuations that were not adequately controlled, were on stable medication regimen, and were able to differentiate between ON and OFF state and troublesome/non-troublesome dyskinesia.1,2
Patients were enrolled at 23 European hospitals, and treatment was randomly assigned 1:1 for either 3 to 8 mg/h of apomorphine or the placebo saline infusion for waking hours for 12 weeks. In the first 4 weeks, the flow rate of the drug was based on individual efficacy and tolerability before entering the 8-week maintenance period. Investigators found that apomorphine significantly reduced OFF time compared with the placebo at –2.47 hours per day and –0.58 hours per day, respectively. Further, the drug was well tolerated without any unexpected safety signals, and 6 individuals in the apomorphine group withdrew due to treatment-related adverse events, according to the study authors.3
"As Parkinson disease progresses, levodopa treatment often becomes less effective at delivering consistent motor control in part due to [gastrointestinal (GI)] dysmotility, variable absorption of oral medication, and the resulting pulsatile stimulation of dopamine pathways in the brain," Stuart Isaacson, MD, director of Parkinson’s Disease and Movement Disorders Center of Boca Raton, Florida, said in the news release. "With Onapgo, the continuous infusion of apomorphine directly stimulates postsynaptic dopamine receptors with no metabolic conversion needed. In addition, the subcutaneous delivery of apomorphine bypasses the GI tract and enters the brain, which can allow for more predictable symptom improvement."1
REFERENCES
1. Supernus announces FDA approval of Onapgo (apomorphine hydrochloride) for Parkinson’s disease. Supernus Pharmaceuticals. February 4, 2025. Accessed February 4, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-announces-fda-approval-onapgotm-apomorphine
2. Clinical Trial of Apomorphine Subcutaneous Infusion in Patients With Advanced Parkinson's Disease (TOLEDO). ClinicalTrials.gov identification: NCT02006121. Updated July 8, 2019. Accessed February 4, 2025. https://clinicaltrials.gov/study/NCT02006121
3. Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson's disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2018;17(9):749-759. doi:10.1016/S1474-4422(18)30239-4
Recent Videos
Related Content
