On demand therapy for Parkinson’s disease patients: Opportunities and choices

Figures & data

Table 1. Pharmacological on-demand treatments for Parkinson’s disease OFF periods

Drug	Indication (US)	Administration	Dose	Efficacy*	Common TEAEs*	Comment
Subcutaneous apomorphine (Apokyn®) [26-29	Indicated for the acute, intermittent treatment of hypomobility, 'off' episodes ('end-of-dose wearing off' and unpredictable 'on/off' episodes) in patients with advanced Parkinson’s disease. Apokyn has been studied as an adjunct to other medications	Subcutaneous injection using Apokyn pen injector and glass cartridge Cartridge contains 3 mL/30 mg apomorphine HCl (10 mg/mL) Single cartridge, pen and needle can deliver doses up to 1 mL (10 mg) in 0.02 mL (0.2 mg) increments Max 5 doses/day	Starting dose 0.2 mL starting dose Titrate up to 0.6 mL depending on effectiveness and tolerance	Time to onset of action: 7.3–22 min Duration of effect: 62.6–96 min Reduction in OFF time: 1) 58% vs placebo 2) 2 hours vs placebo Significant improvement in UPDRS-III scores vs placebo Significant efficacy as recorded by Columbia Parkinson’s disease score	Nausea and/or vomiting Dyskinesia Dizziness/postural hypotension Rhinorrhea Somnolence/drowsiness Yawning Hallucination/confusion Edema/swelling of extremities	Premedicate with antiemetic (e.g. trimethobenzamide) to minimize nausea and vomiting at start of treatment Contraindicated with 5HT3 antagonists, including antiemetics ondansetron, granisetron, dolasetron, palonosetron, alosetron
Sublingual apomorphine (Kynmobi™) [30,31]	Indicated for the acute, intermittent treatment of OFF episodes in patients with Parkinson’s disease	Sublingual film, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg dose strengths Max 5 doses/day	Initial dose 10 mg Titrate up to 30 mg depending on effectiveness and tolerance	Improvement in UPDRS-III score noted at 15 min post dose (1^st measurement timepoint)† Duration of effect: up to 90 min (last timepoint) Significant improvement in UPDRS-III scores vs placebo (LS mean treatment difference vs placebo −7.6 30 min after dosing at week 12) 35% of apomorphine patients turned ON 30 min post dose vs 16% on placebo	Nausea Oral/pharyngeal soft tissue swelling Oral/pharyngeal soft tissue pain and paresthesia Dizziness Somnolence Most common AEs leading to discontinuation were oropharyngeal disorders (17%)	Premedicate with antiemetic (e.g. trimethobenzamide) to minimize nausea and vomiting at start of treatment Contraindicated with 5HT3 antagonists
Inhaled levodopa (Inbrija®) [32-37]	Indicated for the intermittent treatment of OFF episodes in patients with Parkinson’s disease treated with carbidopa/levodopa	Orally inhaled using a provided inhaler and capsules One dose per OFF period Max 5 doses/day	One dose consists of 2 × 42 mg capsules (84 mg)	Improvement in UPDRS-III score noted at 10 min post dose (first measurement timepoint)† Duration of effect: up to 60 min (last timepoint) Significant improvement in UPDRS-III scores vs placebo (LS mean treatment difference vs placebo −3.07 30 min after dosing at week 12 (84 mg)) 58% of Inbrija 84 mg patients turned ON by 60 min post dose vs 36% on placebo	Cough Upper respiratory tract infection Sputum discolored Most common AE leading to discontinuation was cough (2%)	Contraindicated with nonselective MAO inhibitors or in those who have taken a nonselective MAO inhibitor within 2 weeks Not recommended in those with asthma, COPD, or another chronic underlying lung disease

Note: ‘improvements’ are from a predose, OFF state. Negative UPDRS scores represent improvement.

*Summary of double-blind studies. †Subjects were on standard anti-Parkinsonian regimens including levodopa.

AE, adverse event; LS, least squares; TEAE, treatment-emergent adverse event; UPDRS-III, Unified Parkinson Disease Rating Scale Part III (motor).

Olanow CW, Factor SA, Espay AJ, et al. Apomorphine sublingual film for off episodes in Parkinson’s disease: a randomised, double-blind, placebo-controlled phase 3 study. Lancet Neurol. 2020 Feb;19(2):135–144.

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Kynmobi™ (apomorphine hydrochloride) sublingual film (prescribing information) Marlborough, Massachusetts: Sunovion Pharmaceuticals Inc.; 2020 [2020 Jul 2]. Available from: https://www.kynmobi.com/Kynmobi-Prescribing-Information.pdf

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