FDA Accepts APL-130277 Application for OFF Episodes in PD

Antony Loebel, MD, executive vice president and chief medical officer at Sunovion, Head of Global Clinical Development for Sumitomo Dainippon Pharma Group

Antony Loebel, MD

The FDA had accepted a new drug application (NDA) for APL-130277, a sublingual film version of apomorphine, as a treatment for OFF episodes in patients with Parkinson disease (PD), according to a statement from Sunovion Pharmaceuticals, the company developing drug.

Under the Prescription Drug User Fee Act (PDUFA), the FDA will decide on the application by January 29, 2019. The application was based on findings from the phase III CTH-300 trial, in which APL-130277 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 APL-130277 compared with -3.5 with placebo, representing a -7.6 difference between the 2 groups (P = .0002).

“We are encouraged that the FDA has accepted our NDA for apomorphine sublingual film,” Antony Loebel, MD, executive vice president and chief medical officer at Sunovion, Head of Global Clinical Development for Sumitomo Dainippon Pharma Group, said in a statement. “There are currently few treatment options available to Parkinson’s disease patients for the as needed treatment of OFF episodes. We look forward to working with the FDA during the review period so that we can bring a much needed new treatment option to people living with Parkinson’s disease and OFF episodes.”

In the phase III study, APL-130277 was given at a dose of 10 mg to 35 mg in a titration phase to identify a dose required to achieve full ON. In a randomized maintenance phase, patients receive the titrated dose of APL-130277 or placebo. Treatment could be given for 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 APL-130277 over placebo were seen at 15 minutes and continued up to 90 minutes. At week 12, more patients treated with APL-130277 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 APL-130277 compared with just 31.1% for placebo.

Treatment discontinuation was higher in the APL-130277 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 APL-130277 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.

“OFF episodes are disruptive to a person’s daily routine, so a possible treatment that can help alleviate these periods is important for the Parkinson’s disease community and healthcare providers,” Fernando L. Pagan, MD, director of the Movement Disorders Program at Georgetown University Hospital, said in a statement. “These results demonstrate promise for apomorphine sublingual film as a fast-acting medicine for on-demand treatment of all types of motor OFF episodes.”

Early phase studies for APL-130277 were supported by The Michael J. Fox Foundation. If approved, the rapid-acting system could be used by an estimated 350,000 patients with PD in the United States who experienced OFF periods. OFF symptoms typically include impaired movement, muscle stiffness, and tremors.

“Through our ongoing work with people living with Parkinson’s disease, we know the community is eager for more treatment options that may help alleviate OFF episodes, which are often disruptive to their daily lives,” Todd Sherer, PhD, CEO of The Michael J. Fox Foundation for Parkinson’s Research, said in a statement. “We’re heartened to see apomorphine sublingual film is successfully continuing through the regulatory process, and we are hopeful for its approval and future availability.”

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