Kynmobi Safe, Effective for ‘Off’ Periods Over Long Term, Ongoing Trial Reports

Sunovion‘s Kynmobi (apomorphine hydrochloride), a sublingual film treatment for “off” episodes in people with Parkinson’s disease, has a manageable safety profile and maintains efficacy over up to nearly a year of use, interim data from an ongoing Phase 3 trial show.

Findings were presented at MDS Virtual Congress 2020 in the study, “A Long-Term Safety, Tolerability, and Efficacy Study of Apomorphine Sublingual Film for On-Demand Treatment of “OFF” Episodes in Patients With Parkinson’s Disease: Interim Results.”

Parkinson’s is characterized by a loss of dopamine-producing neurons in the brain, and a mainstay of treatment involves therapies to replace dopamine, such as levodopa.

While these treatments help to control symptoms, they can lose effectiveness over time, resulting in “off” periods — those periods when the medication is no longer effective but a new dose cannot yet be taken.

Kynmobi’s active ingredient, apomorphine, is able to get into the brain and mimic the effects of dopamine. It was approved by the U.S. Food and Drug Administration (FDA) as an on-demand treatment for “off” periods in Parkinson’s this year, and recently became commercially available in the U.S.

FDA approval was based on data from a Phase 3 clinical trial (NCT02469090), which showed that Kynmobi more effectively controlled symptoms during “off” periods than a placebo over 12 weeks.

At the recent congress, researchers presented data from an ongoing Phase 3 clinical trial (NCT02542696), observing Kynmobi’s safety, tolerability, and efficacy over up to 48 weeks of use.

Unlike the earlier placebo-controlled trial, this new study is open-label, meaning all of its adult patients are given active treatment.

The study is recruiting both people who participated in previous Kynmobi trials, as well as those who did not. Eligible patients are those with “off” periods while on stable Parkinson’s medications. Contact information for study locations across the U.S., Canada, and Europe is available here.

Enrolled patients first undergo a dose titration period, where they are given increasingly higher doses (10–35 mg at 5 mg increments) of the sublingual (under-the-tongue) film treatment, until they achieve complete control of symptoms during “off” periods within 45 minutes of taking Kynmobi.

After this period, participants enter into the long-term safety phase of the study, where they self-administered their titrated dose for up to five “off” episodes per day.

This trial’s primary goal is to assess the long-term safety of the treatment. The presentation included safety data covering 425 patients.

Most (85%) reported at least one adverse event that emerged following treatment; the most common included nausea (27%), yawning (12%), dizziness (11%), and sleepiness (11%). The most common adverse events affecting the mouth — which are of interest with a sublingual medication — were redness (8%) and lip swelling (5%). Fainting occurred in 2% of participants.

Adverse events led to treatment discontinuation in 31% of participants; the most common reasons for discontinuing were nausea (6%), lip swelling (3%), and dizziness (2%).

Four people died during the course of the study; these deaths were not considered related to Kynmobi’s use.

As a secondary endpoint, participants’ motor symptoms were assessed with the MDS-UPDRS Part III score, a standard measure, where a decrease in scores indicate less severe symptoms. The presentation included efficacy data covering 345 treated patients.

At 24 weeks of treatment, an average decrease in MDS-UPDRS Part III scores of 13.3, 20.1, and 19.2 points within 15, 30, and 60 minutes, respectively, of taking Kynmobi was reported. Similar results were observed at weeks 36 and 48, supporting the treatment’s ability to control “off” episode motor symptoms over months of use.

Most participants also rated themselves as being fully “on” — that is, having total symptom control — within 30 minutes of taking Kynmobi after 24 weeks (74%), 36 weeks (89%), and 48 weeks (84%).

“Interim results up to 48 wks support the LTS [long-term safety] and efficacy of apomorphine sublingual film as an on-demand treatment of ‘OFF’ episodes in patients with PD,” the researchers concluded.