AbbVie Announces Launch of 24-Hour Levodopa Infusion in the European Union

Author(s):

Approved in Europe in late 2022, the 24-hour continuous subcutaneous infusion acts as a novel and effective treatment option for patients with advanced levodopa-responsive Parkinson disease.

Roopal Thakkar

More than a year after it received approval from the European Commission, AbbVie has announced the European market launch of foslevodopa/foscarbidopa (Produodopa), the first and only 24-hour infusion of levodopa-based therapy for patients with advanced Parkinson disease (PD).¹

Prior to the launch, the therapy had received authorization through the Decentralized Procedure in the third quarter of 2022, followed by a CE mark in November of 2023. Also referred to as ABBV-951, this formulation of levodopa and carbidopa prodrugs are delivered as a 24-h/day continuous subcutaneous infusion (CSCI) via an infusion set connected to a portable pump.

"People living with Parkinson disease experience daily challenges and uncertainty, especially as their disease progresses and symptoms are no longer adequately controlled," Roopal Thakkar, senior vice president, Development and Regulatory Affairs, chief medical officer, Global Therapeutics, AbbVie, said in a statement.¹ "This approval is an example of our unwavering commitment to this community by developing new, transformative therapeutic options for people experiencing advanced Parkinson disease, their families, and care partners."

The launch was supported by 3 studies: the phase 3, single-arm, open-label M15-741 (NCT03781167) study, the double-blind, active-controlled M15-736 study (NCT04380142), and a phase 1 pharmacokinetic comparability study. Published in the Journal of Neurology and Therapy, treated patients in M15-741 demonstrated a mean improvement of 3.8 (SD, 3.3) hours of ON time without dyskinesia and –3.5 (SD, 3.1) hours of normalized OFF time while on the therapy over a 52-week period. Additional, at that time, the percentage of patients experiencing morning akinesia dropped from 77.7% to 27.8%.²

In March 2023, AbbVie received a complete response letter by the FDA regarding its new drug application (NDA) submission of its continuous infusion pump.³ The NDA was based on M15-736, a double-dummy trial in which treatment with the therapeutic resulted in increased ON time by 2.72 hours over a 12-week period to 0.97 hours for oral levodopa/carbidopa (LD/CD). Comprising of 130 adults with advanced PD, the trial randomly assigned individuals 1:1 to either ABBV-951 solution as a continuous infusion under the skin plus oral placebo capsules for LD/CD or ABBV-951 as a subcutaneous infusion plus oral capsules containing LD/CD encapsulated tablets.⁴

"This approval represents a significant advancement for those with Parkinson's disease who have historically had limited treatment options for advanced stages,” Angelo Antonini, MD, PhD, professor of neurology at the Department of Neuroscience at the University of Padua, Italy, said in a statement.¹ "When oral treatment no longer sufficiently helps with improvement in motor fluctuations, patients need alternative options. PRODUODOPA's around-the-clock infusion allows for continuous delivery of levodopa, the gold standard of treatment."

The phase 1 trial was a 2-period crossover study that compared the pharmacokinetics of levodopa from AbbVie’s 24-hour foslevodopa/foscarbidopa infusion therapy to the pharmacokinetics of levodopa from 16-hour levodopa-carbidopa intestinal gell, followed by 2 night-time oral levodopa/carbidopa doses. All told, the levodopa exposures were similar between the 2 therapies, leaving investigators to conclude that 24-hour continuous subcutaneous infusion may be safe and beneficial to patients.¹

"As Parkinson disease progresses, it can take a significant physical and emotional toll not only on the person but also on their family and care partners, who often play a critical role in their daily lives,” Josefa Domingos, president of Parkinson’s Europe, said in a statement. “It is vital that the Parkinson community have more options that can help them manage their symptoms."

REFERENCES
1. AbbVie launches PRODUODOPA (foslevodopa/foscarbidopa) for people living with advanced Parkinson disease in the European Union. News release. January 9, 2024. Accessed January 9, 2024. https://www.prnewswire.com/news-releases/abbvie-launches-produodopa-foslevodopafoscarbidopa-for-people-living-with-advanced-parkinsons-disease-in-the-european-union-302028989.html
2. Aldred J, Freire-Alvarez E, Amelin AV, et al. Continuous subcutaneous foslevodopa/foscarbidopa in Parkinson’s disease: safety and efficacy results from a 12-month, single-arm, open-label, phase 3 study. Neurol & Ther. 2023;12:1937-1958
3. AbbVie provides regulatory update on ABBV-951 (foscarbidopa/foslevodopa) new drug application. News release. AbbVie. March 22, 2023. Accessed January 9, 2024. https://news.abbvie.com/article_display.cfm?article_id=12567
4. Soileau MJ, Aldred J, Budur K, et al. Safety and efficacy of continous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson’s disease: a randomized, double-blind, active-controlled, phase 3 trial. Lancet Neurol. 2022;21(12):1099-1109. doi:10.1016/S1474-4422(22)00400-8.