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After receiving a complete response letter from the FDA in January, Sunovion Pharmaceuticals has resubmitted its NDA for apomorphine sublingual film, also known as APL-130277.
Antony Loebel, MD
Sunovion Pharmaceuticals has resubmitted its new drug application (NDA) for its apomorphine sublingual film, also known as APL-130277, to the FDA for the treatment of motor fluctuations in patients with Parkinson disease. This resubmission is in response to a complete response letter (CRL), which the agency sent to Sunovion in January.1
The CRL was issued due to the determination approval could not be completed in its prior form, with the FDA requesting additional information and analyses but no additional clinical studies. This resubmission includes information about intended packaging as well as additional analyses of clinical data.
“Off episodes in people with Parkinson’s disease can occur at any point throughout the day, often occurring in the morning after awakening and periodically throughout the day and can disrupt the ability to perform everyday activities,” Antony Loebel, MD, president, and chief executive officer, Sunovion, said in a statement. “We look forward to continuing our dialogue with the FDA during the review period with the intention of bringing a much needed on-demand treatment option for off episodes to those living with Parkinson’s disease.”
The NDA was based on findings from the phase 3 CTH-300 trial, in which the apomorphine sublingual film demonstrated significant improvements in motor function compared with placebo. The mean change in Unified Parkinson's Disease Rating Scale (UPDRS) part III at 30 minutes post-treatment was —11.1 with APL-130277 compared with –3.5 with placebo at Week 12, representing a –7.6 difference between the 2 groups (P = .0002). Apomorphine sublingual film was administered at 10 mg to 35 mg in a titration phase to identify a dose required to achieve full on time, after which patients received the titrated dose of treatment or placebo, up to 5 times per day for 12 weeks in the randomized maintenance phase. In total, 109 patients with 3.9 median off days at baseline were randomized.2
A similar decline in UPDRS-III was observed at day 1 and weeks 4 and 8. Improvements in UPDRS-III with apomorphine sublingual film over placebo were seen at 15 minutes and continued up to 90 minutes. At week 12, more patients treated with the Sunovion product reported being full on at 30 minutes compared with placebo (P = .04). Additionally, according to home diary entries, 78.7% were on at 30 minutes with apomorphine sublingual film compared with just 31.1% for placebo.
The treatment is a novel formulation of apomorphine and a dopamine agonist. Apomorphine is currently FDA approved for the acute, intermittent treatment of hypomobility and off episodes associated with advanced Parkinson disease, and it is currently available in the US as a subcutaneous injection. Sunovion’s product is intended to rapidly convert those with Parkinson from the off to the on state and has been studied for the treatment of off episodes up to 5 times per day and no sooner than 2 hours from the prior dose.
Treatment discontinuation in the CTH-300 trial was higher in the apomorphine sublingual film arm (27.8%) than the placebo arm (9.1%). Adverse events (AEs) were the most common cause of discontinuation. The most frequent AEs during the maintenance phase for apomorphine sublingual film were nausea (27.8%), somnolence (13%), and dizziness (9.3%). Across the study, there were 6 serious AEs and 1 death reported in the placebo arm.
Sunovion acquired the therapeutic candidate in October 2016 when it acquired Cynapsus Therapeutics Inc. The Michael J. Fox Foundation partly funded 2 phase 1 trials of apomorphine sublingual film—a comparative biostudy in healthy volunteers and a dosing study in patients with Parkinson disease.
1. Sunovion Resubmits New Drug Application for Apomorphine Sublingual Film [press release]. Marlborough, MA: Sunovion; Published November 22, 2019. news.sunovion.com/press-release/sunovion-resubmits-new-drug-application-apomorphine-sublingual-film. Accessed November 25, 2019.
2. Navia B, Factor S, Pahwa R, et al. Efficacy and Safety of Sublingual Apomorphine film (APL-130277) for the Treatment of OFF Episodes in Patients with Parkinson's Disease: Results from a Double-Blind, Placebo-Controlled Trial. Presented at: 2nd Pan American Parkinson's Disease and Movement Disorders Congress; Miami, FL, June 24-28, 2018. LBA03