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Over a 12-week treatment period, treatment with continuous subcutaneous carbidopa/levodopa resulted in significantly greater increase in ON time and reduced OFF time, while demonstrating a safe profile.
Robert A. Hauser, MD
Full results from the phase 3 M15-736 study (NCT04380142) of AbbVie’s investigational agent ABBV-951, a continuous 24-hour subcutaneous infusion of foslevodopa/foscarbidopa, was pubished in Lancet Neurology. The findings showed that the agent significantly improved motor fluctuations in patients with Parkinson disease (PD), with benefits in both ON time without troublesome dyskinesia and OFF time.1
"As a 24-h/day CSCI, foslevodopa-foscarbidopa delivers a wide range of therapeutically relevant doses that can control motor symptoms and reduce motor fluctuations in patients with advanced Parkinson's disease, and offers a potentially safe and effective, individualized, and non-surgical alternative to available treatments,” the study investigators wrote.
In May, AbbVie submitted its new drug application for ABBV-951, with the M15-736 study serving as the basis for the submission. 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 levodopa/carbidopa (LD/CD) or ABBV-951 as a subcutaneous infusion plus oral capsules containing LD/CD encapsulated tablets (n = 67).
Led by Robert A. Hauser, MD, director, Parkinson’s and Movement Disorders Center, University of South Florida, the double-blind, double-dummy, active-controlled study included a screening period (6-60 days), an oral LD/CD 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.
A total of 110 participants completed the trial (ABBV-951: n = 48; placebo: n = 62). The majority of participants in both treatment groups (70.2%; 99 of 141) were taking additional concomitant PD medications other than immediate-related LD/CD at baseline before randomization. All told, the study met the primary efficacy outcome, as ABBV-951 significantly improved ON time without troublesome dyskinesia at week 12 compared with standard oral LD/CD (2.72 h [SE, 0.52] vs 0.97 h [SE, 0.50]; difference, 1.75 h; 95% CI%, 0.46-3.05; P = .0083).
The 26-patient trial includes 10 individuals with early-manifest Huntington disease on low-dose AMT-130 and 16 in the high-dose cohort, which will continue enrollment after a DSMB found no further safety concerns.
Similarly, treatment with the AbbVie product demonstrated a significant improvement in OFF time at week 12 compared with standard care LD/CD (model-based mean change: –2.75 h [SE, 0.50] vs –0.96 h [SE, 0.49]; difference, –1.79 h; 95% CI, –3.03 to –0.54; P = .0054). These improvements were observed as earlier as the first post-baseline assessment and continued to the end of the double-blind treatment period. Additionally, fewer participants on ABBV-951 reported being OFF at the time of waking relative to those on oral LD/CD (8 of 47 [17%] vs 38 of 60 [63%]) despite the oral LD/CD group including night-time oral dosing if needed.
Between the 2 groups, 85% of those on ABBV-951 and 63% of those on oral LD/CD had at least 1 adverse event (AE), most of which were non-serious and mild or moderate in severity. Serious AEs were similar between the 2 arms (8% vs 6%); however, the incidence of infusion site AEs were higher in the ABBV-951 group, with erythema (27%), pain (26%), cellulitis (19%), and oedema (12%) at the infusion site being the most frequently reported. None of the infusion site AEs resulted in systemic complications.
Falls were reported in 6 (8%) of 74 participants in the continuous LD/CD group and 12 (18%) of 67 in the oral LD/CD group. Hallucinations or psychosis events, were found in 15% of those on ABBV-951 and 3% of those on oral LD/CD. A higher rate of patients discontinued treatment with ABBV-951 due to AEs, with infusion site AEs (cellulitis: 5%), pain (4%), bruising (3%), hemorrhage (3%), and oedema (3%) as the most common reasons. No deaths were reported in the ABBV-951 group, and 1 participant had a serious AE leading to death in the oral LD/CD group, which was considered not related to the study drug.
