Carbidopa/Levodopa

Onapgo is approved for adult Parkinson’s patients experiencing motor fluctuations. Credit: Inside Creative House via Getty Images. Supernus Pharmaceuticals has won US approval for its wearable pump Onapgo (apomorphine hydrochloride) to treat symptoms of Parkinson’s disease. Supernus’ regulatory path for Onapgo has been marked by multiple setbacks over nearly five years, with the Food and Drug Administration (FDA) rejecting three prior applications before securing approval. The company acquired Onapgo, previously known as SPN-830, from US WorldMeds in 2020. Soon after, Supernus submitted its first application for FDA review. However, in 2020, the agency issued a refusal-to-file (RTF) letter, determining that the submission was incomplete and not ready for formal review. Supernus resubmitted the application twice, receiving complete response letters (CRLs) both times. The first 2022 rejection required further analysis of the infusion device and drug product, while the most recent CRL, issued in April 2023, cited product quality concerns and deficiencies in the master file for the proprietary pump. The company resubmitted its fourth application in August, leading to the current approval. Onapgo will now be available for adult Parkinson’s disease patients experiencing motor fluctuations. The wearable pump is designed to provide a continuous subcutaneous infusion of Supernus’ apomorphine (Apokyn). The drug is intended for patients experiencing “off” periods, where medication wears off and symptoms return or worsen. The approval is based on a Phase III, 12-week study (NCT02006121) involving 107 patients. Onapgo led to a drop in daily “off” time and an increase in daily good “on” time, defined as periods without dyskinesia and the patient’s global impression of change (PGIC). Supernus plans to launch Onapgo in the second quarter of 2025, supported by a team of specialists, a nurse education programme, and access support services. The approval adds Onapgo to a growing list of infusion-based Parkinson’s treatments. AbbVie ’s Vyalev (foscarbidopa and foslevodopa), a continuous subcutaneous infusion therapy combining prodrugs of carbidopa and levodopa, was approved in October 2024 after three regulatory attempts. The FDA’s initial rejection of Vyalev did not involve efficacy or safety concerns but requested additional information on the pump device. The second rejection followed findings of issues at a third-party manufacturer. AbbVie set a precedent in 2015 with its Parkinson’s disease infusion pump therapy Produodopa (foslevodopa foscarbidopa), sparking innovation in drug delivery systems as companies looked for alternatives for conventional oral treatments.

iStock, avgust01 Before garnering approval on Tuesday, Onapgo had been rejected twice by the FDA. The FDA on Tuesday signed off on Supernus Pharmaceuticals’ apomorphine hydrochloride injection—to be marketed under the brand name Onapgo—for use in adults with Parkinson’s disease. According to Jefferies analysts, this approval gives Supernus access to a U.S. market opportunity worth between $100 million and $300 million. The company expects to launch Onapgo in the second quarter of this year, and while there has been no announcement yet of its price, Jefferies expects it to be broadly in line with AbbVie’s Vyalev, a similar drug-device product for Parkinson’s that has an annual wholesale acquisition cost of approximately $119,000. “To us, Vyalev and Onapgo seem fairly comparable in terms of efficacy,” the Jefferies analysts wrote, though they pointed to several distinguishing factors for Supernus, including a “potentially better tolerability profile” and different mechanism of action. Doctors “may want to switch MOAs as patients progress further in their disease,” the analysts contended. Onapgo is a drug-device combination that allows for the continuous subcutaneous infusion of apomorphine and is indicated for the treatment of motor fluctuations in Parkinson’s disease patients. Onapgo’s label is relatively clean, with safety precautions for patients taking certain nausea medications—including ondansetron and granisetron—and for those who are allergic to any of the infusion’s ingredients. The FDA’s approval on Tuesday was backed by data from a Phase III trial, which enrolled 107 patients and showed that Onapgo led to a significant drop in daily off time and elicited a significant increase in daily good on time. These treatment benefits became apparent as early as one week after treatment initiation and were sustained through the duration of the study. In a statement, Supernus CEO Jack Khattar said that Onapgo’s approval gives prescribers “a novel approach for adults with Parkinson’s disease who are experiencing motor fluctuations.” Tuesday’s approval is the culmination of what has been a difficult regulatory road for Onapgo. In October 2022, the FDA rejected Supernus’ drug application, citing the need for additional information regarding the infusion device, as well as more analysis of the drug product. The regulator at the time identified several areas of deficiencies, including labelling, product quality, risk analysis and manufacturing. Two years later, in April 2024, the FDA again hit Supernus with a Complete Response Letter, pointing to two specific areas where it needed additional information: product quality and the infusion device. At the time, Supernus emphasized that the regulator had not flagged issues with the drug’s clinical safety or efficacy.