Kynmobi (apomorphine) for Parkinson’s disease
What is Kynmobi for Parkinson’s disease?
Kynmobi (apomorphine hydrochloride), now discontinued in the U.S., was an approved sublingual or under-the-tongue therapy used to reduce off episodes occurring with standard levodopa treatment in people with Parkinson’s disease. Off episodes are periods when a medication wears off between doses and disease symptoms are not well controlled.
The therapy was developed by Sunovion Pharmaceuticals. However, the company voluntarily withdrew the medication from the U.S. market in June 2023 due limited use. A similar discontinuation is expected in Canada in September 2023.
|Chemical Name:||Apomorphine hydrochloride|
|Usage:||Add-on therapy to reduce off episodes in Parkinson’s patients|
|Administration:||Oral film placed under the tongue|
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 of the disorder may worsen between doses — the so-called off periods.
Kynmobi was a fast-acting, thin-strip film coated with apomorphine, a small molecule that binds to and activates dopamine receptor proteins, mimicking the effect of dopamine in the brain. As such, the therapy was expected to reduce off episodes in Parkinson’s patients.
Kynmobi was approved by the U.S. Food and Drug Administration (FDA) in May 2020 for the treatment of short-term, intermittent off episodes in people with Parkinson’s disease. It was approved in Canada one month later.
However, the company decided to discontinue the medication in both countries in 2023 due limited use.
Who should not take Kynmobi?
Kynmobi was not designed for use in combination with 5HT3 antagonists, a type of therapy used to prevent and treat nausea and vomiting. This contraindication was due to an increased risk of extremely low blood pressure and loss of consciousness.
Patients also were advised not to use Kynmobi if they had a known allergy to the treatment or any of its ingredients, which include a sulfite called sodium metabisulfite.
The treatment also was generally not recommended for patients with a major psychotic disorder, due to a risk of psychosis exacerbation.
Kynmobi was 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 was placed under the tongue, dissolving in approximately three minutes.
For patients first starting the therapy, there was a titration kit — essentially a starter kit — containing 10 sealed foil pouches, two of each dose strength. The approved starting dosage was 10 mg, which could be adjusted in 5 mg increments, based on efficacy and tolerability, up to a maximum single dose of 30 mg.
The first dose was designed to be given when the patient was in an off state and under the supervision of a healthcare professional who could monitor blood pressure and pulse. Any dose adjustments also had to be monitored by a healthcare provider.
Each Kynmobi dose was to be taken at least two hours apart, for a maximum of five daily doses. If one dose of the therapy was ineffective during an off episode, a second dose was not recommended to be administered during that same off episode.
The therapy was designed to be taken whole, and not broken, chewed, or swallowed. It was recommended patients drink water to moisten their mouth before taking the medication, as that helped the film dissolve more easily.
As nausea and vomiting were common side effects of Kynmobi, patients could be given the anti-nausea medication trimethobenzamide before or during treatment, as needed.
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.
Phase 3 trial
The trial enrolled patients who were experiencing at least one off episode a day, lasting two or more hours, while on levodopa treatment.
After an initial period that aimed to find the optimal Kynmobi dose for each patient, participants were randomly assigned to receive either their optimal dose 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. That reduction was 11.1 versus 3.5 points. The therapy also was generally well tolerated.
Long-term Phase 3 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 goal was to determine the long-term safety and efficacy of Kynmobi.
After a dose-titration period in which the optimal dose for each patient was determined, all participants received the therapy for up 48 weeks, or about one year. 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 faster and stronger 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
A Europe-based Phase 3 study (NCT03391882), completed in August 2021, compared Kynmobi with under-the-skin (subcutaneous) apomorphine injections, an older approved formulation. That trial involved 113 Parkinson’s patients treated with levodopa who were experiencing at least two hours of off time per day. Although data were not yet been published at the time of the therapy’s discontinuation, results posted on the trial’s page had suggested that the sublingual formulation was at least not inferior to the also approved under-the-skin formulation.
The most common side effects of Kynmobi that had been reported in clinical trials included:
- swelling, pain, or abnormal sensations in the mouth
- sleepiness or daytime somnolence.
Nausea and vomiting
Patients could experience nausea and vomiting while on Kynmobi. As such, treatment with the anti-nausea medication trimethobenzamide, at a dose of 300 mg three times a day, was considered for some individuals both before and during Kynmobi treatment. Trimethobenzamide was advised to be continued only as long as was necessary, and not for periods longer than two months.
Falling asleep during daily activities
There were 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, had to be assessed by and discussed with prescribing healthcare providers.
In cases of sudden sleeping episodes, it had been advised that Kynmobi be discontinued. If treatment was not stopped, patients were advised to avoid driving and other activities where falling asleep unexpectedly could have been dangerous.
Low blood pressure, fainting, and fall risk
Kynmobi could cause low blood pressure that may have resulted in dizziness, lightheadedness, or fainting for patients when rising from sitting or lying down. The therapy also could increase the risk of falls by simultaneously lowering blood pressure and changing mobility. Therefore, it had been recommended that patients taking the therapy be monitored for blood pressure.
The medication could cause swelling, pain, and abnormal sensations of the mouth. Symptoms for patients had included a burning or prickling of the mouth, as well as mouth sores commonly known as canker sores. These symptoms in some cases required treatment interruption or discontinuation, if severe. Patients were advised not to return to treatment after discontinuation, as oral side effects could recur after restarting and be more severe than the previous reactions.
Hallucinations, psychosis, and impulse control
Kynmobi had been known to cause mental health issues, including hallucinations (seeing or hearing things that are not real), confusion, and psychotic behaviors, for some patients. The therapy generally was not recommended for patients with a known psychotic disorder, as it could aggravate psychotic symptoms.
Problems with impulsive control, such as urges to gamble, binge eating, or increased sexual urges, also could occur while on Kynmobi. If these happened, healthcare providers were recommended to consider reducing the dose or discontinuing treatment.
Hemolytic anemia and heart problems
There were reports of heart rhythm abnormalities in patients on under-the-skin formulations of apomorphine, which suggests that Kynmobi also could cause such complications. It had been recommended that the therapy’s potential risks and benefits be carefully weighed before treatment was started in patients with known risk factors for heartbeat abnormalities.
Kynmobi also had been reported to cause hemolytic anemia, a condition characterized by the excessive destruction of red blood cells. If a patient developed anemia, or low red blood cell counts, while on the medication, a workup for hemolytic anemia had been recommended. Treatment discontinuation could be considered if the condition was confirmed.
Tissue changes and painful erections
Scarring-like tissue changes in the pelvis, lungs, and heart were reported in some people treated with medicines similar to Kynmobi. The changes could resolve for some patients after treatment discontinuation, but not all individuals experienced a complete resolution.
Patients treated with Kynmobi could experience long-lasting and painful erections, which, if severe, may have required surgery. Patients who experienced this complication were advised to inform their healthcare provider and seek help in the nearest hospital emergency room.
Use in pregnancy and breastfeeding
Adequate clinical data on the effects of Kynmobi in pregnancy did not exist. However, findings from animal models had suggested the medication may cause harm to a developing fetus. As such, patients who were or planned to become pregnant were recommended to discuss this topic with their healthcare providers.
It remains unknown if Kynmobi could pass into breast milk, and whether it could have any harmful effects on infants or on milk production in nursing patients. Those who had planned to breastfeed while using the medication had been advised to inform their healthcare team and carefully weigh the potential benefits and risks of using the medication while nursing.
Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
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