After resubmitting the NDA for apomorphine sublingual film (APL-130277), the FDA has set the new PDUFA action date of May 21, 2020.
Antony Loebel, MD
Sunovion Pharmaceuticals has announced that the FDA has moved forward with filing its new drug application (NDA) for apomorphine sublingual film, also known as APL-130277, in the treatment of motor fluctuations—off episodes—in patients with Parkinson disease.1
In January, the FDA sent a complete response letter (CRL) to Sunovion in response to its original filing, requesting additional information and analyses but no additional clinical studies. After then resubmitting the application in November, this acceptance has set the Prescription Drug User Fee Act (PDUFA) action date of May 21, 2020.
“The unpredictable nature of off episodes can be extremely challenging and disruptive to the daily lives of people living with Parkinson’s disease as well as their care partners,” Antony Loebel, MD, president and chief executive officer, Sunovion, said in a statement. “We look forward to working with the FDA over the remaining review period.”
WATCH NOW: What Is OFF in Parkinson Disease?
The NDA was based on data 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 at week 12 was -11.1 with Apomorphine sublingual film compared with -3.5 with placebo, representing a -7.6 difference between the 2 groups (P = .0002).2
Apomorphine sublingual film was manufactured to be used in on-demand treatment of all types of motor off episodes, including morning and unpredictable off, delayed/partial on, and end-of-dose wearing off episodes. As Sunovion noted in its release, these episodes are experienced by 40% to 60% of patients, with limited treatment options available to treat them.
In the CTH-300 study, apomorphine sublingual film was given at doses of 10 mg to 35 mg in a titration phase to identify a dose required to achieve full on. Then, in a randomized maintenance phase, the titrated dose or placebo were administered, given up to 5 times per day for 12 weeks. Overall, 109 patients with 3.9 median off days at baseline were randomized.
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 study drug reported being full on at 30 minutes compared with placebo (P = .04). According to home diary entries, 78.7% were on at 30 minutes with apomorphine sublingual film compared with just 31.1% for placebo.
“People with Parkinson's have shared that OFF episodes can be disruptive and hamper their quality of life. New treatments could mean greater symptom control for more people, improving their ability and confidence to navigate daily life with the disease,” said Todd Sherer, PhD, CEO, The Michael J. Fox Foundation for Parkinson’s Research, in a statement.
As for safety in CTH-300, treatment discontinuation was higher in the apomorphine sublingual film arm (27.8%) compared with placebo (9.1%), with adverse events (AEs) representing the most common cause. 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.
1. Sunovion Announces FDA Filing Acceptance of Resubmitted New Drug Application for Apomorphine Sublingual Film [press release]. Malborough, MA: Sunovion; Published December 20, 2019. news.sunovion.com/press-release/sunovion-announces-fda-filing-acceptance-resubmitted-new-drug-application-apomorphine. Accessed December 20, 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