Written and Reviewed by Team Pharmacally

Introduction
The U.S. Food and Drug Administration (FDA) has recently given the green light to Onapgo (apomorphine hydrochloride), a subcutaneous injection designed for the acute treatment of motor fluctuations in adults with advanced Parkinson’s disease (PD). This product was developed by Supernus Pharmaceuticals, a biopharmaceutical company dedicated to creating and marketing treatments for central nervous system (CNS) disorders. Onapgo stands out as the first and only subcutaneous apomorphine infusion device aimed at addressing motor fluctuations. It is a wearable device that delivers continuous treatment throughout the day, helping to manage off time more effectively. This approval represents a major step forward in alleviating the challenging “off” episodes that many PD patients face, providing a quick and dependable therapeutic solution.
Understanding Motor Fluctuations in Parkinson’s Disease
Motor fluctuations in Parkinson’s disease (PD) refer to the changes in movement control that occur as the disease progresses, often as a result of long-term levodopa use, the main medication for symptom management. These fluctuations happen because the brain’s ability to store and regulate dopamine diminishes over time, leading to alternating periods of good mobility (“on” periods) and poor mobility (“off” periods). Initially, patients may enjoy stable symptom relief from levodopa, but as the disease progresses, the duration of this relief shortens, and movement challenges become more unpredictable. A common type of motor fluctuation is the “wearing-off” phenomenon, where the effects of levodopa diminish before the next scheduled dose, resulting in a return of symptoms like tremors, rigidity, and bradykinesia (slowness of movement). Another type, known as “delayed-on” or “dose failure,” occurs when a dose of medication takes longer than anticipated to take effect or fails to provide relief altogether. Additionally, some patients experience “on-off” fluctuations, where they switch unpredictably between ease of movement and difficulty, even when medication levels are stable.
Managing motor fluctuations requires careful adjustments to medication timing, dosage, or formulation. Physicians might suggest more frequent doses, extended-release options, or incorporating additional medications like dopamine agonists, COMT inhibitors, or MAO-B inhibitors to help stabilize these fluctuations. In more advanced situations, treatments such as continuous levodopa infusion or deep brain stimulation (DBS) could be explored to achieve more reliable symptom management.
Onapgo’s Mechanism of Action
Onapgo™ (apomorphine hydrochloride) is a medication that has been approved to treat motor fluctuations, often called “off” episodes, in adults suffering from advanced Parkinson’s disease. The active component, apomorphine, is a non-ergoline dopamine agonist that mainly targets D2-type dopamine receptors in the brain. By activating these receptors, Onapgo aids in reducing motor symptoms like tremors, rigidity, and bradykinesia (slowness of movement) that occur during off periods. It is delivered continuously via a subcutaneous infusion, providing a consistent dose of apomorphine throughout the day. This delivery method avoids the gastrointestinal tract, allowing the medication to enter the bloodstream directly and reach the brain more reliably. Consequently, patients benefit from more stable symptom management and less off time.
Clinical Efficacy Supported by Phase 3 Trials
The Phase III TOLEDO study was a randomized, double-blind, placebo-controlled clinical trial that assessed the efficacy and safety of continuous subcutaneous apomorphine infusion (Onapgo) in patients with Parkinson’s disease (PD) who were struggling to manage their motor fluctuations. The trial included 107 participants who had been diagnosed with PD for at least three years and were experiencing an average of three or more hours of “off” time each day, despite having optimized their oral medication regimens. During the 12-week treatment period, participants received either Onapgo or a placebo infusion. The results showed that those who received Onapgo had a significant reduction in daily “off” time, averaging nearly two hours less per day compared to the placebo group. This decrease in “off” time was also associated with an increase in “on” time without troublesome dyskinesia. Furthermore, a larger percentage of patients treated with Onapgo achieved at least a two-hour reduction in daily “off” time compared to those on placebo. The study highlighted that the continuous infusion of apomorphine provided more predictable symptom relief by bypassing the gastrointestinal tract and directly stimulating dopamine receptors in the brain. Common side effects included nodules at the infusion site, nausea, drowsiness, redness at the infusion site, dyskinesia, headaches, and insomnia. These results contributed to the U.S. Food and Drug Administration’s approval of Onapgo in February 2025 as a treatment option for managing motor fluctuations in adults with advanced Parkinson’s disease.
Safety Profile and Administration Guidelines
Common side effects may include nausea, dizziness, sleepiness, and reactions at the injection site, as well as infusion site redness, dyskinesia, headaches, and insomnia. Importantly, Onapgo has warnings regarding hypotension, fainting, and QT prolongation. It is contraindicated to use it alongside 5-HT3 antagonists (like ondansetron) due to the risk of severe hypotension. Healthcare providers should start dosing in clinical environments to ensure tolerability is monitored. Patients and their caregivers are trained to give the injection subcutaneously in the abdomen or thigh, with a maximum recommended dose of 0.6 mL for each episode.
A Step Forward in Parkinson’s Care
A well-known specialist in movement disorders stated, “Onapgo addresses a significant need by offering a quick-acting, user-friendly solution for off episodes. Its swift action allows patients to take back control during unexpected fluctuations.” This approval highlights the FDA’s dedication to meeting the needs in neurodegenerative diseases. For the Parkinson’s disease community, Onapgo symbolizes hope for improved independence and quality of life, emphasizing the crucial role of innovation in managing chronic conditions.
Conclusion
Onapgo’s arrival offers a pragmatic solution for advanced PD patients grappling with motor fluctuations. By combining rapid efficacy with a user-friendly delivery system, it stands as a valuable addition to the therapeutic arsenal against Parkinson’s disease, highlighting progress in personalized and responsive care.
References:
1. FDA Approves Onapgo (apomorphine hydrochloride) for the Treatment of Motor Fluctuations in Adults with Advanced Parkinson’s disease, Drugs.com, 04 Feb 2025
2. Katzenschlager, Regina et al., Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial, The Lancet Neurology, Volume 17, Issue 9, 749 – 759
3. Regina Katzenschlager, Werner Poewe, Olivier Rascol, 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, Volume 83, 2021, Pages 79-85, https://doi.org/10.1016/j.parkreldis.2020.12.024
4. Henriksen, T., Katzenschlager, R., Bhidayasiri, R. et al.Practical use of apomorphine infusion in Parkinson’s disease: lessons from the TOLEDO study and clinical experience. J Neural Transm130, 1475–1484 (2023). https://doi.org/10.1007/s00702-023-02686-7
5. Highlights of prescribing information, ONAPGO (apomorphine hydrochloride) injection, for subcutaneous use, available from https://www.onapgo.com/onapgo_PI.pdf
6. What Are Parkinson’s disease Motor Fluctuations?, WebMD, 29 August 2024
7. Cardoso, Francisco et al., Fluctuations in Parkinson’s disease: progress and challenges, The Lancet Neurology, Volume 23, Issue 5, 448 – 449
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