The FDA has approved Sunovion Pharmaceuticals’ apomorphine sublingual film (also known as APL-130277) for the treatment of motor fluctuations, or off episodes, in patients with Parkinson disease.1 The drug will be marketed under the name Kynmobi.
Notably, it is the first therapy for OFF episodes associated with Parkinson disease that is administered sublingually.
“Despite the significant prevalence—experienced by up to 60% of people with PD, within 4 to 6 years of diagnosis—and impact of off episodes, most treatments for off episodes have focused on keeping people on versus treating episodes when they occur,” Stacy Wu, MD, head, Global Clinical Research, Neurology, Sunovion, told NeurologyLive. “With apomorphine sublingual film, patients will have a new treatment option, with a novel route of administration, that can quickly improve mobility when disruptive off episodes occur. In a clinical trial, initial improvements in motor symptoms were observed in as little as 15 minutes post-dose.”
Additionally, Wu noted that it is common for patients with Parkinson disease to experience gastrointestinal (GI) tract issues that can, in turn, result in a slowed absorption of oral levodopa/carbidopa. “The novel sublingual administration allows for the delivery of apomorphine through the oral mucosa, bypassing the GI tract and avoiding levodopa absorption issues common in Parkinson patients,” Wu said.
The resubmitted new drug application (NDA) was supported by 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 a reduction of 11.1-point with apomorphine sublingual film compared with a decline of 3.5 points with placebo, representing a 7.6-point difference between the 2 groups (P = .0002).2,3
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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 to the apomorphine group (n = 54) or placebo group (n = 55). 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, continuing 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 in the apomorphine sublingual film group compared with just 31.1% of the placebo group within 2 days prior to their in-office visit (P <.001). When assessing all diary entries, 77% of patients using apomorphine sublingual film reported achieving a full on response at 30 minutes post-dose compared with 26% of the placebo group. Notably, a similar response rate was recorded throughout the day, with 71% reported full on between 5AM and 9AM and 86% reported full ON between 10PM and 5AM.4
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.
Wu told NeurologyLive that the open-label extension study of apomorphine sublingual film for the acute treatment of off episodes in patients with Parkinson is currently ongoing (NCT02542696). It has a current target enrollment of 226 participants and is anticipating completion in March 2023.
“Sunovion is evaluating the longer-term, clinical development plans for other products in our robust pipeline and the potential to leverage the sublingual technology and delivery mechanism for other therapies in development,” Wu said.
In January 2019, the FDA sent a complete response letter (CRL) to Sunovion in response to its original filing in mid-2018 for the sublingual film, requesting additional information and analyses but no additional clinical studies. After then resubmitting the application in November 2019, its acceptance set its Prescription Drug User Fee Act (PDUFA) action date for this month.
Apomorphine sublingual film is meant 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. Sunovion has noted in releases that these episodes are experienced by 40% to 60% of patients, and limited treatment options are available to treat the population. This treatment joins Acorda’s inhaled levodopa (Inbrija) and US WorldMeds' apomorphine hydrochloride injection (Apokyn) as one of the few acute treatment options for off episodes.
1. Sunovion Announces U.S. FDA Approval of Kynmobi (apomorphine hydrochloride) Sublingual Film for the Treatment of Parkinson’s Disease OFF Episodes. News Release. Sunovion; May 21, 2020. Accessed May 21, 2020. https://www.businesswire.com/news/home/20200521005786/en/Sunovion-Announ...
2. Sunovion Announces FDA Filing Acceptance of Resubmitted New Drug Application for Apomorphine Sublingual Film [press release]. Sunovion; Published December 20, 2019. Accessed May 21, 2020. news.sunovion.com/press-release/sunovion-announces-fda-filing-acceptance-resubmitted-new-drug-application-apomorphine
3. 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
4. Hauser R, Mehta S, Maulis M, et al. Patient-reported motor responses to apomorphine sublingual film based on home dosing and response diaries. Presented at: 2020 Pan American Parkinson’s Disease & Movement Disorders Congress. February 14-16, 2020; Miami, FL.