Kynmobi (Apomorphine HCl)

Kynmobi (apomorphine hydrochloride) is a sublingual or under-the-tongue formulation of apomorphine developed by Sunovion to reduce off episodes in Parkinson’s disease. Off episodes occur when symptoms reappear as a therapy wears off, before the next dose takes effect.

The U.S. Food and Drug Administration (FDA) approved Kynmobi in May 2020 and the treatment became available in the U.S. later that year.

It can be taken up to five times per day and dissolves under the tongue.

A similar medication, called Apokyn and marketed by Supernus Pharmaceuticals, also is approved to treat off episodes in these patients. However, Apokyn is an injection treatment with side effects that can cause pain and injection-site reactions.

How does Kynmobi work?

Parkinson’s is characterized by a loss of nerve cells in the brain. This causes a decrease in dopamine, an important signaling molecule. Many treatments for Parkinson’s disease aim to increase dopamine levels in the brain either by reducing dopamine clearance or increasing dopamine secretion.

However, in between medication doses, patients — especially those with more advanced disease — often experience so-called off periods. This is when their dopamine levels dip low, leading to a worsening of symptoms.

Kynmobi, called APL-130277 during development, is a fast-acting, thin-strip film coated with apomorphine that is given noninvasively through the lining of the mouth, from a disintegrating strip placed under the tongue.  Apomorphine is a small molecule that binds to the dopamine receptors and activates them, mimicking the effect of dopamine in the brain.

Kynmobi in trials for Parkinson’s disease

Sunovion sponsored a Phase 3 clinical trial (NCT02469090) that recruited 141 Parkinson’s patients who were taking levodopa and experiencing at least one off episode a day, lasting at least two hours. During the trial, participants were given either Kynmobi or a placebo for 12 weeks, or about three months, and could take the medication up to five times each day. To analyze the effects of the treatment, researchers used the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part 3 score, looking at the pre-dose period to 30 minutes after dosing at week 12. Of note, part 3 of the MDS-UPDRS scale is used to evaluate Parkinson’s motor symptoms.

Initial topline results from 109 patients indicated a significant improvement in MDS-UPDRS scores in those using Kynmobi compared with those who received the placebo. Patients also tolerated the treatment well. The most common side effects were nausea, sleepiness, and dizziness.

Another Phase 3 clinical trial (NCT02542696), slated for completion in July 2022, is underway in 226 Parkinson’s patients at sites across the U.S., Canada, and Europe. The aim of this open-label study is to determine the long-term safety and efficacy of Kynmobi. Previous data from this trial supported Kynmobi treatment as safe and effective for roughly one year of use.

Data from these two Phase 3 studies also found that treatment with Kynmobi was associated with greater and faster motor improvement than levodopa among Parkinson’s patients experiencing off episodes, supporting its use in patients with delayed responses to levodopa.

Another Phase 3 trial (NCT03391882) compared treatment with Kynmobi to that of subcutaneous (under-the-skin) apomorphine injections in 113 patients with Parkinson’s treated with levodopa who experienced at least one off episode per day, during the waking day, that lasted more than two hours.

Other information

Kynmobi was approved by the FDA as a sublingual film at 10 mg, 15 mg, 20 mg, 25 mg, and 30 mg doses, to be taken as needed up to a maximum of five times a day. Each use of the treatment should be at least two hours apart, with a maximum single dose of 30 mg.

Simultaneous use of Kynmobi with serotonin blockers (5HT3 antagonists), a type of therapy used to prevent and treat nausea and vomiting, is contraindicated. Patients also should avoid Kynmobi if they have hypersensitivity (exaggerated or inappropriate immunologic reactions) to apomorphine or any of its ingredients.

Nausea, vomiting, mouth irritation, dizziness, and daytime somnolence are the most common side effects. Other adverse reactions may occur, such as falls, high fever, confusion, hallucinations, or psychotic-like behavior.

Using Kynmobi together with medications to treat hypertension or vasodilators may increase the risk for low blood pressure (hypotension), cardiac problems, falls, and injuries.

Additional information may be found in the therapy’s label.

 

Last update: Feb. 09, 2022, by Teresa Carvalho MS

 


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