FDA Approves AbbVie’s 24-Hour Foscarbidopa/Foslevodopa Pump for Advanced Parkinson Disease Treatment

According to a new announcement, the FDA has approved AbbVie’s foscarbidopa/foslevodopa, marketed as Vyalev, as the first and only subcutaneous 24-hour infusion of levodopa-based therapy for the treatment of motor fluctuations in adults with advanced Parkinson disease (PD). The company noted that timing for a patient's access to the therapy is dependent on their individual insurance plan, with coverage for Medicare patients expected in the second half of 2025.¹

“Overall, there is great excitement around the approval of Vyalev. While there are numerous options for the symptomatic treatment of PD, the options become limited as the disease progresses, and patients experience motor fluctuations despite their current treatment," Pavnit Kukreja, PharmD, senior director, neuroscience, US Medical Affairs, AbbVie, told NeurologyLive®. "Previously, only more invasive options, such as surgery, existed. Vyalev offers the ability to continuously deliver the gold standard, levodopa, without surgery, over the morning, day, and night."

The approval was supported by data from the phase 3 M15-736 study (NCT04380142) that assessed the efficacy of continuous subcutaneous infusion of foscarbidopa/foslevodopa, also known as ABBV-951, among adult patients with advanced PD compared with oral immediate-release carbidopa/levodopa (CD/LD IR), along with a 52-week, open-label M15-741 study (NCT03781167) which investigated the long-term safety and efficacy of the treatment. Results from the M15-736 study revealed that patients who received foscarbidopa/foslevodopa reported superior improvement in motor fluctuations, with increased ON time without troublesome dyskinesia and decreased OFF time, compared with oral CD/LD IR.

"The phase 3 study demonstrated superior efficacy over oral IR CD/LD with regards to improvement in On time without troublesome dyskinesia, and the adverse events were mostly mild to moderate and nonserious. We are committed to improving the lives of people impacted by PD and transforming the standard of care with this first-of-its-kind therapeutic option," Kukreja added.

In May 2022, AbbVie submitted its new drug application (NDA) for ABBV-951, with M15-736 serving as the basis for the submission.² The study included 141 adult participants who were randomized 1:1 to either ABBV-951 solution (n = 74) as a continuous infusion under the skin plus oral placebo capsules for CD/LD or ABBV-951 as a subcutaneous infusion plus oral capsules containing CD/LD encapsulated tablets (n = 67).

"For too long, the Parkinson's community has had limited treatment options for advanced disease. Due to the progressive nature of the disease, oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required," Robert A. Hauser, MD, MBA, professor of neurology and director of the Parkinson's and Movement Disorder Center at the University of South Florida, said in a statement.¹ "This new, non-surgical regimen provides continuous delivery of levodopa morning, day and night."

Led by Hauser, the double-blind, double-dummy, active-controlled study included a screening period (6-60 days), an oral CD/LD stabilization period (2-3 weeks), a double-blind treatment period (12 weeks) for a total of 13 scheduled visits. Eligible participants were at least 30 years old with a diagnosis of idiopathic and levodopa-responsive PD and had inadequately controlled motor fluctuations with an average OFF time of at least 2.5 h/day over 3 consecutive days.

Published in Lancet Neurology, ABBV-951 also showed a good safety profile in the phase 3 study, with most of the reported adverse events (AEs) either mild or moderate in a nature.³ Serious AEs occurred in 8% ABBV-951 group compared with 6% in the CD/LD group. Notably, there as 1 death recorded in the study, believed to be from a treatment-emergent AE while in the CD/LD group. At week 12, ABBV-951-treated patients showed a decrease of 2.75 hours in OFF time, with changes observed as early as the first week. In comparison, those in the oral CD/LD group demonstrated decreases of 0.96 hours during the same stretch (P = .0054).

In May 2023, the FDA issued the first CRL to AbbVie for its investigational 24-hour continuous foscarbidopa/foslevodopa pump. In the CRL, the agency requested additional information on the pump as part of its review, but did not request AbbVie to conduct additional efficacy and safety trials related to the drug.⁴

In January 2024, AbbVie announced the European market launch of foslevodopa/foscarbidopa (Produodopa), the first and only 24-hour infusion of levodopa-based therapy for patients with advanced PD more than a year after it received approval from the European Commission.⁵ 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.

The launch was supported by 3 studies: the phase 3 M15-741 study, the double-blind, active-controlled M15-736 study, 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%.⁶

In June 2024, the FDA again issued a complete response letter (CRL) to the company's NDA for ABBV-951.⁷ In the CRL, the agency cited observations identified during inspection of a third-party manufacturer listed in the NDA. The inspection at the facility did not involve ABBV-951 or any of the company's medicine. The CRL did not identify any issues in terms of safety, efficacy, or labeling of ABBV-951, including the device. Furthermore, the letter did not request that the company perform additional efficacy and safety studies related to the drug or device-related testing.

"People living with advanced Parkinson's disease experience daily challenges as a result of uncertainty in managing motor fluctuations, especially as their disease progresses," Roopal Thakkar, MD, executive vice president, research & development, and chief scientific officer, AbbVie, said in a statement.¹ "We are proud to bring this innovation to patients who may benefit from motor symptom control through continuous 24-hour administration of Vyalev."

REFERENCES
1. U.S. FDA Approves VYALEV™ (foscarbidopa and foslevodopa) for Adults Living with Advanced Parkinson's Disease. News Release. AbbVie. Published October 17, 2024. Accessed October 17, 2024. https://news.abbvie.com/2024-10-17-U-S-FDA-Approves-VYALEV-TM-foscarbidopa-and-foslevodopa-for-Adults-Living-with-Advanced-Parkinsons-Disease
2. AbbVie submits new drug application to US FDA for investigational ABBV-951 (foscarbidopa/foslevodopa) for the treatment of advanced Parkinson disease. News release. AbbVie. May 20, 2022. Accessed October 17, 2024. https://www.prnewswire.com/news-releases/abbvie-submits-new-drug-application-to-us-fda-for-investigational-abbv-951-foscarbidopafoslevodopa-for-the-treatment-of-advanced-parkinsons-disease-301551779.html?tc=eml_cleartime
3. 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.
4. AbbVie provides regulatory update on ABBV-951 (foscarbidopa/foslevodopa) new drug application. News release. AbbVie. March 22, 2023. Accessed October 17, 2024. https://news.abbvie.com/article_display.cfm?article_id=12567
5. AbbVie launches PRODUODOPA (foslevodopa/foscarbidopa) for people living with advanced Parkinson disease in the European Union. News release. January 9, 2024. Accessed October 17, 2024. https://www.prnewswire.com/news-releases/abbvie-launches-produodopa-foslevodopafoscarbidopa-for-people-living-with-advanced-parkinsons-disease-in-the-european-union-302028989.html
6. 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
7. AbbVie Provides U.S. Regulatory Update on ABBV-951 (Foscarbidopa/Foslevodopa). News Release. AbbVie. Published June 25, 2024. Accessed October 17, 2024. https://news.abbvie.com/2024-06-25-AbbVie-Provides-U-S-Regulatory-Update-on-ABBV-951-Foscarbidopa-Foslevodopa