KYNMOBI (Sublingual Apomorphine Film) – A New Drug Approved in US By FDA

05Oct

KYNMOBI (Sublingual Apomorphine Film)

The U.S. Food and Drug Administration has approved Sunovion’s Kynmobi (apomorphine hydrochloride) as an on-demand sublingual treatment for off episodes, or times when medication wears off, in people with Parkinson’s disease.

Apomorphine subcutaneous injection is an approved treatment for Parkinson’s patients experiencing off episodes for more than 2 decades which is readily available in Australia.

Its efficacy in easing motor symptoms is established, but it can pose significant challenges to patients, such as the need for an under-the-skin injection, an initial dose titration that should be supervised in a clinic, and common side effects such as nausea and injection site complications. These challenges are thought to have limited its use.

This new treatment has ease of use as it is like a wafer which can be kept under the tongue. It 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, can 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. since September 2020.

At the MDS virtual 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 its adult patients are given active treatment.

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%).

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 long-term safety and efficacy of apomorphine sublingual film as an on-demand treatment of ‘OFF’ episodes in patients with PD,” the researchers concluded.

Potential benefits may include quick treatment of “off” time (which might offer a bridge until the next dose of scheduled medication kicks in); the security of knowing a “rescue” is there if needed, which might expand social or exercise opportunities; and others.

Possible side effects could include tongue soreness or swelling, nausea, sleepiness or dizziness. This drug also does not replace a person’s daily Parkinson’s medications, but is an add-on, as-needed therapy.

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.