General Information

Kynmobi (apomorphine hydrochloride) is a a non-ergoline dopamine agonist.

Kynmobi is specifically indicated for the acute, intermittent treatment of “off” episodes in patients with Parkinson’s disease.

Kynmobi is supplied as a sublingual film. Kynmobi must be administered whole. Do not to cut, chew, or swallow Kynmobi. Kynmobi will disintegrate in about 3 minutes. Because of the high incidence of nausea and vomiting with Kynmobi when administered at recommended doses, an antiemetic, beginning 3 days prior to the initial dose of Kynmobi, is recommended. Treatment with the antiemetic should only be continued as long as necessary to control nausea and vomiting, and generally no longer than two months after initiation of treatment with Kynmobi. Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of apomorphine with drugs of the 5HT3 antagonist class including antiemetics (for example, ondansetron, granisetron, dolasetron, palonosetron) and alosetron are contraindicated.

The dose range for Kynmobi is 10 mg to 30 mg per dose, administered sublingually, as needed, for the acute, intermittent treatment of “off” episodes. Doses should be separated by at least 2 hours. If a single dose of Kynmobi is ineffective for a particular “off” episode, a second dose should not be given for that “off” episode. The efficacy or safety of administering a second dose for a single “off” episode has not been studied. Do not administer more than 5 doses per day. The maximum single dose of Kynmobi is 30 mg.

The initial dose is 10 mg. Dose initiation should occur when the patient is in an “off” state and in a setting where a healthcare provider can monitor blood pressure and pulse. If the patient tolerates the 10 mg dose, and responds adequately, the starting dose should be 10 mg, used on an as needed basis, up to 5 times per day, to treat “off” episodes. If the dose is tolerated but the response is insufficient, the patient’s usual Parkinson’s disease medications should be resumed and up-titration with Kynmobi continued generally within 3 days. Increase dosage by increments of 5 mg and assess response. Continue to titrate in a similar manner, under the supervision of a healthcare provider, until an effective and tolerable dose is achieved.

Mechanism of Action

Kynmobi (apomorphine hydrochloride) is a a non-ergoline dopamine agonist. Kynmobi is a non-ergoline dopamine agonist with high in vitro binding affinity for the dopamine D4 receptor, and moderate affinity for the dopamine D2, D3, and D5, and adrenergic α1D, α2B, α2C receptors. The precise mechanism of action of Kynmobi as a treatment for “off” episodes associated with Parkinson’s disease is unknown, although it is believed to be due to stimulation of post-synaptic dopamine D2-type receptors within the caudate-putamen in the brain.

Clinical Trial Results

The FDA approval of Kynmobi was based on a phase 3 randomized, double-blind, placebo-controlled, parallel-group study in 109 patients. At baseline, the mean number of daily “off” episodes was 4 and the mean duration of “off” episodes was slightly over an hour in both groups. The study included a titration phase and a 12-week maintenance phase. Patients were titrated to the dose that achieved a full “on” response and was tolerated during the titration phase. Patients were treated with an oral antiemetic starting 3 days before the titration phase. In the titration phase, patients (N=141) arrived at the study site in an “off” state having not taken their regular morning dose of carbidopa/levodopa or any other adjunctive PD medications, as well as having taken their last dose of carbidopa/ levodopa and any other adjunctive PD medications no later than midnight the night before. Treatment was initiated in the clinic with a 10 mg dose of Kynmobi. If the patient responded to treatment and tolerated the 10 mg Kynmobi dose, the patient was randomized in a blinded fashion to Kynmobi or placebo in a 1:1 ratio. If the patient tolerated the dose but did not adequately respond, the patient was asked to return to the clinic within 3 days and the dose was increased by 5 mg. The titration process was continued up to a maximum Kynmobi dose of 35 mg or until a full “on” was achieved as determined by the investigator and the patient. Dose administration was permitted up to five times per day in the maintenance phase. Data demonstrated that patients with PD receiving Kynmobi experienced significant improvements in motor symptoms at 30 minutes after dosing at week 12, with a mean reduction of 7.6 points, compared to placebo, on the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score. Initial clinical improvements were seen at 15 minutes post-administration. Additionally, a significantly higher percentage of people treated with Kynmobi had a patient-rated full ON response within 30 minutes at week 12, compared with people receiving placebo.