Last updated Jan. 26, 2023, by Teresa Carvalho, MS
Fact-checked by Marta Figueiredo, PhD
What is Kynmobi for Parkinson’s disease?
Kynmobi (apomorphine hydrochloride) is an approved sublingual or under-the-tongue therapy used to reduce “off” episodes between doses of standard levodopa treatment in people with Parkinson’s disease. So-called off episodes are periods when a medication wears off and disease symptoms are not well-controlled.
Formerly known as APL-130277, the therapy was developed by Sunovion.
How does Kynmobi work?
Parkinson’s is caused by the progressive loss of dopamine-producing nerve cells in the brain. Dopamine is an important brain signaling molecule that plays a role in a range of functions from movement to memory.
Many treatments for Parkinson’s disease, such as levodopa, aim to increase dopamine levels in the brain, either by reducing dopamine clearance or increasing its production. However, long-term use of levodopa-based treatments can lead to a reduction in efficacy, meaning that symptoms may worsen between doses — the so-called off periods.
Kynmobi is a fast-acting, thin-strip film coated with apomorphine, a small molecule that binds to and activates dopamine receptors proteins, mimicking the effect of dopamine in the brain. As such, the therapy is expected to reduce off episodes in Parkinson’s patients.
Who can take Kynmobi?
The U.S. Food and Drug Administration (FDA) approved Kynmobi in May 2020 for the treatment of short-term, intermittent off episodes in people with Parkinson’s. The treatment was approved in Canada one month later.
Who should not take Kynmobi?
Kynmobi should not be taken in combination with 5HT3 antagonists, a type of therapy used to prevent and treat nausea and vomiting. This class of medicines include ondansetron, granisetron, dolasetron, and palonosetron, as well as alosetron — used for nausea specifically associated with irritable bowel syndrome.
Patients also should avoid Kynmobi if they have a known allergy to the treatment or any of its ingredients, which include a sulfite called sodium metabisulfite.
Also, the therapy is generally not recommended for patients with a major psychotic disorder, due to a risk of psychosis exacerbation.
How is Kynmobi administered in Parkinson’s disease?
Kynmobi is available as a rectangular blue to green film with a white printed number identifying the dose strength: 10 mg, 15 mg, 20 mg, 25 mg, or 30 mg. The film is placed under the tongue, dissolving in three minutes.
For patients initiating the therapy, there is a titration kit containing 10 sealed foil pouches, two of each dose strength. The approved starting dosage is 10 mg, which can be adjusted in 5 mg increments based on efficacy and tolerability up to a maximum single dose of 30 mg.
The first dose should be given when the patient is in an off state and under the supervision of a healthcare professional who can monitor blood pressure and pulse. Any dose adjustments also should be monitored by a healthcare provider.
Each Kynmobi dose should be taken at least two hours apart, to a maximum of five daily doses. If one dose of the therapy is ineffective during an off episode, a second dose should not be administered during that same off episode.
The therapy should be taken whole, not broken, chewed, or swallowed. It’s recommended that patients drink water to moisten their mouth before taking the medication as this will helps the film dissolve more easily.
The medication should be stored at room temperature.
Kynmobi in clinical trials for Parkinson’s disease
Phase 3 trial [OR CTH-300 trial]
The FDA’s approval of Kynmobi was supported by positive data from a North American Phase 3 clinical trial (NCT02469090) that tested the therapy against a placebo in 109 adults with Parkinson’s. All were experiencing at least one off episode a day, lasting two or more hours, while on levodopa treatment.
After an initial period of treatment that aimed to find the optimal Kynmobi dose for each patient, participants were randomly assigned to receive either the therapy or a placebo, up to five times a day, for 12 weeks, or about three months.
The trial’s main goal was to assess changes in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part 3 score from the pre-dose period to 30 minutes after dosing at week 12. Part 3 of the MDS-UPDRS scale is used to evaluate Parkinson’s motor symptoms, with higher scores indicating worse disability.
The results showed a significantly greater reduction in MDS-UPDRS scores among Kynmobi-treated patients compared with those who received the placebo. The therapy also was generally well-tolerated.
Long-term Phase 3 trial [OR CTH-301 trial]
Another Phase 3 clinical trial (NCT02542696), completed in November 2022, enrolled 427 Parkinson’s patients at sites across the U.S., Canada, and Europe. The aim was to determine the long-term safety and efficacy of Kynmobi.
All participants received the therapy for up to about one year, after a dose-titration period in which the optimal dose for each patient was determined. Interim data supported Kynmobi treatment as safe and effective at reducing off episodes over the long term.
In addition, results from these two Phase 3 studies showed that Kynmobi treatment 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.
European Phase 3 trial [OR CTH-302 trial]
A Europe-based Phase 3 trial (NCT03391882), completed in August 2021, compared Kynmobi to under-the-skin (subcutaneous) apomorphine injections, an already approved formulation at the time, in 113 Parkinson’s patients treated with levodopa who were experiencing at least two hours of off time per day. Although data have not yet been published, results posted in the trial’s page suggest that the sublingual formulation is at least not inferior to the approved under-the-skin formulation.
Common side effects of Kynmobi
The most common side effects related to the treatment with Kynmobi are:
- swelling, pain, or abnormal sensation in the mouth
- sleepiness or daytime somnolence.
Nausea and vomiting
Patients may experience nausea and vomiting while on Kynmobi. As such, it’s recommended that patients start the anti-nausea therapy trimethobenzamide (300 mg three times a day) three days before the first Kynmobi dose. Treatment with trimethobenzamide should only be continued as long as needed, and not for longer than two months.
Falling asleep during daily activities
There are reports of people experiencing drowsiness or sleepiness and, in some cases, falling asleep during daily activities while on Kynmobi. Before initiating treatment, any risk factors for increased sleepiness, such as other co-prescribed medications and sleep disorders, should be assessed by and discussed with prescribing healthcare providers.
In case of sudden sleeping episodes, Kynmobi should be discontinued. If treatment is not stopped, patients should avoid driving and other activities where falling asleep unexpectedly is dangerous.
Low blood pressure, fainting, and fall risk
Kynmobi can cause low blood pressure that may lead patients to experience dizziness, lightheadedness, or fainting when rising from sitting or lying down. The therapy also may increase the risk of falls by simultaneously lowering blood pressure and changing mobility. Therefore, it is recommended that patients be monitored for blood pressure.
The medication may cause swelling, pain, and abnormal sensations, such as burning or prickling, of the mouth, as well as mouth sores common known as canker sores. These symptoms may require treatment interruption or discontinuation if severe. Patients are advised not to return to treatment after discontinuation as oral side effects may recur and may be more severe than the previous reactions.
Hallucinations, psychosis, and impulse control
Kynmobi may cause mental health issues, including hallucinations (seeing or hearing things that are not real), confusion, and psychotic behaviors. The therapy is generally not recommended for patients with a known psychotic disorder, as it can aggravate psychotic symptoms.
Problems with impulsive control, such as urges to gamble or increased sexual urges, also may occur while on Kynmobi. If these do happen, patients are advised to reduce the dose or discontinue the treatment.
Withdrawal-related high fever and confusion
High fever and confusion following rapid dose reduction or discontinuation of Parkinson’s therapies have been reported.
There have been reports of heart rhythm abnormalities in patients on apomorphine-based treatments, delivered under the skin, which suggests that Kynmobi could cause such complications. The therapy’s potential risks and benefits should be carefully weighed before the start of treatment in patients with known risk factors for heartbeat abnormalities.
Tissue changes and painful erections
Scarring-like tissue changes in the pelvis, lungs, and heart have been reported in some people treated with medicines similar to Kynmobi.
Patients treated with Kynmobi may experience long-lasting and painful erections, which if severe, may require surgery. In the presence of this complication, patients should inform their healthcare provider and seek help in the nearest hospital emergency room.
Use in pregnancy and breastfeeding
Kynmobi has not been thoroughly studied in those who are pregnant or breastfeeding. Animal data have suggested that it may cause harm to a developing fetus. There are no data on the presence of Kynmobi in human milk, the effects on a breastfed infant, or the effects on milk production in nursing patients.
Patients who are pregnant or nursing, or planning to become pregnant or breastfeed should discuss this topic with their healthcare providers.
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