Sublingual Film Turns Parkinson’s Off Periods ‘Full On,’ Most Patients in Phase 3 Trial Report

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by Forest Ray PhD |

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Phase 3 trial analysis

A majority of Parkinson’s patients in a clinical trial reported achieving a fully “on” response within 30 minutes of taking Sunovion‘s under-the-tongue apomorphine film, called APL-130277, about three months after starting its use to counter “off” episodes in this disease, a post-hoc analysis of study results found.

At week 12, 79% of the 54 adults using APL-130277 in the Phase 3 trial (NCT02469090) recorded a “full on” response to the at-home treatment as the effectiveness of their stable levodopa (or similar dopamine treatment) waned, scientists reported. These responses were a secondary study goal.

Results were presented at the recent Pan American Parkinson’s Disease & Movement Disorders Congress (MDS-PAS), Sunovion said in an email that also provided the presentation. It was titled “Patient-Reported Motor Responses to Apomorphine Sublingual Film Based on Home Dosing and Response Diaries.”

Meant to provide on-demand and fast-acting relief from all types of off episodes, APL-130277 is a formulation of apomorphine in a thin film. The film is placed under the tongue (called a sublingual medication), where it is absorbed into the bloodstream. This makes it easy to self-administer at any time and any place.

Apomorphine stimulates the production of dopamine in the brain. Dopamine is a powerful messenger molecule called a neurotransmitter produced in dopaminergic neurons. Dopaminergic neurons die off in Parkinson’s disease, which leads to the loss of motor and cognitive skills characteristic of the disease.

Off episodes are periods of worsening Parkinson’s symptoms that usually occur when a medication like levodopa begins to lose effect, but before the next dose can be taken. These symptoms include tremors, rigidity, and slowness, as well as cognitive impairment and mood disorders.

The Phase 3 trial randomly assigned 109 patients, with 54 given APL-130277 for on-demand and at-home use, and 55 others a placebo. All enrolled had reported experiencing one off period each day, and were currently taking stable doses of levodopa and adjunctive medications.

The study was double-blinded, so neither the patients nor the researchers knew who received the medication and who was using a placebo.

Over the course of its 12 weeks, patients recorded the time they took APL-130277 during any off episode they chose to treat, and their resulting motor status (full on or off) 30 minutes later. This information was self-reported in diaries over the two days prior to each clinic visit, made at study weeks four, eight and 12.

Researchers measured the percentage of “full on response” reports. That response was defined as one providing benefits “with regard to mobility, stiffness, and slowness, whereby normal daily activities could be performed and were comparable to or better than normal response to [Parkinson’s] medications prior to study enrollment.”

At the study’s conclusion, 79% of patients using the investigative film reported being fully on at 30 minutes after taking APL-130277, compared to 31% of those on placebo.

Across all weeks of diary entries, 77% of patients using APL-130277 reported full-on responses, compared to 26% on a placebo. All took either the treatment or placebo a mean of 2.2 and 2.5 times each day.

Those with full-on response also said they achieved it at all times of the day, with 71% reporting it between 5 am and 9 am, and 86% overnight, between 10 pm and 5 am. This is important, as off episodes can occur at any time.

“Based on home dosing and response diaries, the self administration of APL may lead to a FULL “ON” response in most patients experiencing “OFF” episodes throughout the day,” the researchers concluded.

APL-130277 is currently under review by the U.S. Food and Drug Administration for possible approval as a sublingual treatment for off periods in Parkinson’s disease. A decision is expected on or before May 24.

Meanwhile, enrollment is continuing in an open-label extension Phase 3 study (NCT02542696) investigating the long-term safety and efficacy of APL-130277. Patients are still being recruited at sites in Los Angeles and in several European countries. More information can be found here.