Regulatory Decision Summary for Kynmobi

The clinical assessment and regulatory recommendations for Kynmobi (apomorphine) sublingual film was based on the combined evidence of efficacy and safety from a single placebo-controlled pivotal study, with supporting data from clinical pharmacology studies conducted in both healthy volunteers and patients with Parkinsons Disease and from additional safety and efficacy studies.

Kynmobi was found to be efficacious in improving "OFF" symptoms in levodopa-responsive patients who were up-titrated in the dose range of 10 milligrams (mg) to 30 mg. The therapeutic effect was reasonably robust with meaningful improvement in motor functions. This finding was supported by the primary analysis and supportive sensitivity analyses.

The identified therapeutic benefits included motor function improvements in the majority of patients (with a notable placebo effect). About a quarter of these patients achieved motor function improvement that fits the criteria of the "ON" state (the number-needed to treat was about 10 for 1). The long-term benefits are uncertain, as the average duration of patient participation ranged between 150 and 200 days.

The therapeutic delivery required medical supervision to titrate the patient to the optimal dose to reach individualised therapeutic effect, with adequate training for self-administration or with help from a caregiver for maintenance treatment at home.

The identified harms include the commonly observed oropharyngeal adverse reactions. When some of the cases are hypersensitivity in nature, even with symptoms of an anaphylactic reaction, no cases of full anaphylactic reaction were reported. In patients with hypersensitivity symptoms, Kynmobi re-challenge is not recommended.

Orthostatic hypotension, especially in patients with a history of hypotension, cardiovascular disease, and on anti-hypertensive medications have been reported. The likelihood of adverse reaction was high, given that the patients tended to be elderly with other comorbidities. Drug interaction with nitroglycerin resulted in significant hypotension, in some cases. It likely increased the risk of hypotension in patients having a heart attack and taking nitroglycerin. Moderate tendency of corrected QT Interval (QTc) prolongation was identified which may have lead to drug interactions with other medications and disease conditions. The likelihood of a QTc prolongation was high if safety warnings were not heeded. There were reports of adverse reactions in patients with Parkinsons Disease receiving levodopa and dopaminergic treatments. These adverse reactions are well documented and in the literature in advanced patients receiving multiple drug treatments. These warnings have also been included in the Canadian Product Monograph for Kynmobi.

When used as instructed in suitable patients as per the Product Monograph, the benefit-risk-uncertainty profile of Kynmobi is considered favourable, under medical supervision.