Sunovion’s Request for Approval of Under-the-Tongue Apomorphine to Treat ‘Off’ Periods Under FDA Review

The U.S. Food and Drug Administration (FDA) has accepted for review its request to approve apomorphine sublingual film (APL-130277) as a quick-acting, oral treatment of the motor fluctuations, or off episodes, associated with Parkinson’s disease.

Sunovion, which is developing the potential therapy, submitted a new drug application, or NDA, to the agency in April and the FDA’s decision is expected to by Jan. 29, 2019.

“We are encouraged that the FDA has accepted our NDA for apomorphine sublingual film,” Antony Loebel, executive vice president and chief medical officer at Sunovion, said in a press release.

“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,”Loebel added.

Parkinson’s patients treated for long periods with levopoda, the most common first-line treatment for disease symptoms like tremors and stiffness, can develop motor fluctuations — “off-time” periods characterized by the return of these symptoms — as well as dyskinesia, or involuntary movements. These episodes occur as the result of the drug wearing off.

About half of all patients taking levodopa eventually experience off episodes, which become more frequent and severe as the disease worsens. Off periods can occur at any time — unpredictably or as a dose nears its end — although they frequently happen shortly after a patient awakens in the morning.

Despite its impact, therapies targeting off episodes in advanced patients are limited – the only approved medicine in the U.S. is apomorphine, marketed under the brand name Apokyn (apomorphine hydrochloride, US WorldMeds), administered as a subcutaneous injection. Its mode of administration can cause pain and injection-site reactions.

Sunovion’s apomorphine (APL-130277) was developed as an oral (under the tongue), on-demand and fast-acting therapy to lessen all types of motor off episodes. The company designed it to be taken up to five times a day.

It works by mimicking the action of dopamine, a neurotransmitter that facilitates communication between nerve cells. Parkinson’s motor impairments are caused by the death of dopamine-producing nerve cells in the brain.

Sunovion’s supported its FDA application with data from a 12-week Phase 3 study (NCT02469090) that tested the therapy’s effectiveness and safety in Parkinson’s patients whose levodopa had worn off.

Researchers measured its efficacy within 30 minutes after dosing, and looked at the percentage of patients who achieved a full response within that time window. The treatment met the study’s study goal, with initial results of 109 treated adults showing at 30 minutes a statistically significant mean reduction in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part 3 score, a measure of Parkinson’s motor symptoms, compared to placebo at week 12.

Results also showed the therapy was well-tolerated, and continued to show persistent effects through 90 minutes after dosing, when a final measure was taken.

“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,” said Todd Sherer, PhD, CEO of The Michael J. Fox Foundation for Parkinson’s Research. “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.”

The clinical development of apomorphine was partly supported by the Fox Foundation.