Those who received an infusion of ABBV-951, consisting of foslevodopa/foscarbidopa, showed statistically significant increases in hours of ON time without troublesome dyskinesia compared with oral levodopa/carbidopa.
ABBV-951 (AbbVie), a continuous 24-hour subcutaneous infusion of foslevodopa/foscarbidopa, met its primary end point and demonstrated superior performance to levodopa/carbidopa (LD/CD) in reducing motor fluctuations of patients with advanced Parkinson disease (PD) in a phase 3 randomized active-controlled study.1
The phase 3 M15-736 study (NCT04380142) was a double-blind, double-dummy trial that compiled 130 adult participants with advanced PD and split them into 2 treatment arms. In the first arm, participants received the ABBV-951 solution as a continuous infusion under the skin plus oral placebo capsules for LD/CD. In the second arm, participants received placebo for ABBV-951 as a continuous subcutaneous infusion plus oral capsules containing LD/CD encapsulated tablets.
Over the course of a 12-week treatment period, patients on ABBV-951 demonstrated increases of 2.72 hours in ON time compared to 0.97 hours for oral LD/CD (P = .0083). These improvements, documented using the Parkinson’s Disease Diary, were observed as early as the first week and persisted through the end of the study period. AbbVie noted that full results from the study will be presented at a future medical meeting or submitted for publication in a peer-reviewed journal.
Treatment with ABBV-951 also resulted in a decrease of 2.75 hours in OFF time, which was observed after the first week and continued through week 12. In comparison, those in the oral LD/CD group demonstrated decreases of 0.96 hours during the same stretch (P = .0054).
"Parkinson's disease is a progressive, irreversible neurological disease with debilitating symptoms that can make daily life challenging,” Michael Severino, MD, vice chairman and president, AbbVie, said in a statement.1 "We're committed to addressing the continued needs of patients and are encouraged by these results that highlight a potential alternative treatment option for those affected by advanced Parkinson's disease."
Most of the reported adverse events (AEs) associated with ABBV-951 were mild or moderate in nature. Serious AEs were found in 8% in the ABBV-951 group and 6% in the LD/CD group. There was 1 death recorded in the study, believed to be from a treatment-emergent AE while in the LD/CD group.
Erythema, pain, cellulitis, edema, bruising, hemorrhage, nodule, induration, infection, and pruritus, all infusion site AEs, were among the most reported (≥5%) in the ABBV-951 group. Additional commonly reported AEs included dyskinesia, ON and OFF phenomenon, fall, hallucinations, balance disorder, constipation, and peripheral swelling. Although infusion site AEs were more common in the ABBV-951 group, most of them were considered non-serious, mild to moderate in severity, and were resolved with or without treatment. Notably, none of these led to systemic complications.
AEs leading to discontinuation from the study occurred in 21.6% of those on ABBV-951, compared to 1.5% in the oral LD/CD group. Hallucination and psychosis AEs, also more frequently reported in the ABBV-951 group, were non-serious and mild to moderate in severity. Additionally, there were less falls and associated injuries in the ABBV-951 group.
"Patients need more therapeutic options to control their symptoms and troublesome dyskinesia for this debilitating disease," principal investigator Jason Aldred, MD, FAA, clinical associate professor, University of Washington, and clinical assistant professor, Washington State University Elson S. Floyd College of Medicine, said in a statement.1 "These data are promising and demonstrate positive results on a key endpoint used to assess efficacy of treatments for patients with advanced Parkinson."
For years, the combination of LD/CD has been the standard of care for symptom management in patients with PD. In January 2015, AbbVie received FDA approval for Duopa, the first, and to date only, treatment providing 16 continuous hours of LD/CD together to help control motor fluctuations in advanced PD.2 The eternal suspension is administered using a small, portable infusion pump that delivers LD/CD directly into the small intestine through a tube placed during an outpatient procedure.
The new mechanism of ABBV-951 has several advantages over the percutaneous endoscopic transgastric jejunostomy (PEG-J) tube through which Duopa is administered. David Standaert, MD, PhD, chair of the Department of Neurology at the University of Alabama at Birmingham and a consultant for AbbVie, told NeurologyLive in May that, "the need for levodopa comes out of what happens in advanced PD, where patients develop wearing off of their medications. About 50% of patients at 5 years will experience wearing off, and there are ways to treat wearing off with oral medications, but many times we get to the point where you cannot control the wearing off anymore."
Although patients with PD have benefited greatly from Duopa, issues with tube clogging and breakage can occur, and endoscopy is required when a tube needs replacement. If ABBV-951 continues to prove its success, it could be implemented in-office, with no need for the necessary gastroenterologist involvement and potential complications that come with a PEG-J tube.