KYNMOBI™ (apomorphine hydrochloride)
KYNMOBI™ (apomorphine hydrochloride) is the first and only sublingual therapy indicated for the on-demand treatment of OFF episodes in Parkinson’s disease.
Developed by Sunovion Pharmaceuticals, the new drug application (NDA) for KYNMOBI was submitted to the US Food and Drug Administration (FDA) in March 2018 and accepted for review in June 2018.
Sunovion received a Complete Response Letter (CRL) from the FDA in January 2019 requesting additional data. Sunovion resubmitted the NDA to FDA in November 2019 by including details of the packaging and additional analysis of clinical data.
The FDA approved KYNMOBI for the treatment of short-term, intermittent OFF episodes in people with Parkinson’s disease in May 2020. KYNMOBI was approved by Health Canada for the acute and intermittent treatment of OFF episodes in Parkinson’s disease patients in June 2020.
KYNMOBI is a prescription medicine and will be available as a sublingual film, which can be used up to five times per day at doses ranging between 10mg and 30mg. The drug is anticipated to be available in the US by September 2020.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that occurs when nerve cells, or neurons, are damaged or die in a brain field that regulates movement. These neurons normally produce a chemical in the brain known as dopamine in the substantia nigra. If the neurons are damaged or become dysfunctional, less dopamine is produced leading to kinetic or movement issues.
The disease induces shaking, trembling, and difficulty in walking, standing and coordinating. The symptoms of the disease usually start gradually and get worse over time. Patients may experience difficulty in walking and talking and significant changes in behaviour in addition to sleep problems, depression, impaired memory and tiredness.
The OFF episode in PD is the re-emergence or deterioration of motor and non-motor symptoms normally controlled by oral levodopa and carbidopa. These episodes normally occur in the morning after waking up and during the day.
Symptoms of OFF episodes may include tremor, rigidity, and slow motion, bowing down posture, balance disturbance, communication problems, anxiety and symptoms of depression.
KYNMOBI is a non-ergoline agonist of dopamine with a strong in vitro binding affinity to the dopamine D4 receptor and intermediate affinity to the dopamine D2, D3, and D5 receptors, and to the adrenergic dopamine α1D, α2B, α2C receptors.
The exact mechanism of action of KYNMOBI as a therapy for OFF episodes Parkinson’s disease is unknown, although it is assumed to work by activating post-synaptic D2-type dopamine receptors within the caudate-putamen in the brain.
KYNMOBI dissolves under the tongue to improve OFF symptoms of PD as needed.
FDA approval of KYNMOBI was based on randomised, double-blind, placebo-controlled, parallel-group, phase three clinical trial called CTH-300 conducted in patients experiencing OFF episodes with PD.
The study included patients suffering from PD for a median duration of nine years and in the Hoehn and Yahr Phase III or less. Patients received a steady dosage of concomitant levodopa for at least four weeks prior to screening.
A total of 109 patients were randomised in a 1:1 ratio to receive either 10mg KYNMOBI or placebo. The study included a titration phase and a maintenance phase of 12 weeks.
The titration process was subsequently increased to a maximal dosage of 35mg KYNMOBI or until the full “on” was achieved as decided by the investigator and the patient. The administration of dose was allowed up to five times a day in the maintenance phase.
The study’s primary endpoint was the mean shift from pre-dose to 30 minutes post-dose in Movement Disorder Society-Unified Parkinson’s Disease Rating Scale, Part III (MDS-UPDRS III) during the maintenance phase.
KYNMOBI treatment group exhibited a minimum-square mean improvement of -11.1 points compared to -3.5 points for the placebo group.
Common adverse reactions observed during the study were dizziness, oropharyngeal reactions, nausea, and somnolence.
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