Sunovion Pharmaceuticals’ apomorphine sublingual under-the-tongue film (APL-130277) — now under review for approval — significantly improved motor fluctuations, or off episodes, in Parkinson’s patients in Phase 3 clinical trial, results show.
The double-blind pivotal study, (NCT02469090), evaluated the efficacy and safety of APL-130277 as a fast-acting oral treatment for Parkinson’s patients with off periods, including those experiencing early morning off episodes. These episodes typically occur in the period between the waning of benefits of medications such as levodopa and the time a next dose can be taken, when motor symptoms re-emerge.
A total of 109 patients were given either APL-130277 (54) or placebo (55). Their mean age was 62, and they had been diagnosed with Parkinson’s for a mean of nine years.
Results were presented at the 2nd Pan American Parkinson’s Disease and Movement Disorders Congress (MDS-PAS) that recently ended in Miami.
Compared to those on placebo, patients given APL-130277 had a statistically significant difference of 7.6 points in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score, a measure of motor skills and function. This test was preformed in patients just prior to treatment and again 30 minutes after dosing at week 12.
A statistically significant difference from placebo was seen as early as 15 minutes post-dose and persisted up to 90 minutes, the last time point measured. Similar improvements were observed in the double-blind maintenance period measured at baseline and at weeks 4, 8 and 12.
APL-130277 also led to a higher percentage of treated patients with a full on response — or control of motor symptoms — within 30 minutes at week 12.
Apomorphine sublingual (under-the-tongue) film was generally well-tolerated, with most treatment-related side effects being mild to moderate, and reversible, after its use was discontinued. Nausea, sleepiness, and dizziness were the most frequent adverse effects reported in the maintenance phase.
“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 press release.
Pagan added that the results show promise for APL-130277 “as a fast-acting medicine for on-demand treatment of all types of motor off episodes.”
Sunovion intends APL-130277 to be a treatment for all types of off episodes, those that are unpredictable as well as those that occur at the end-of-dose or in the morning hours after awakening. The formulation is designed to be taken up to five times a day.
About half of all Parkinson’s patients taking levodopa experience off periods, which become more frequent and severe with disease s progression. Apomorphine is the only approved medication for off episodes in the U.S., available as Apokyn (apomorphine hydrochloride, US WorldMeds). But Apokyn is an injection treatment.
Sunovion recently announced that the U.S. Food and Drug Administration has accepted for review its request to approve APL-130277 to treat off episodes in Parkinson’s. The FDA’s decision is expected by Jan. 29, 2019.