A critical review of apomorphine hydrochloride sublingual film for the treatment of Parkinson’s disease ‘OFF’ episodes

ABSTRACT

Introduction: Parkinson’s disease (PD) is a neurodegenerative disorder defined by its motor features. Levodopa therapy is the gold standard therapy, but over time, response is impeded by the development of motor fluctuations, including ‘off’ episodes where PD symptoms reemerge. Sublingual apomorphine offers a new, novel, and effective therapy developed for treatment of ‘off’ episodes.

Areas covered: Apomorphine is an old dopamine agonist developed as a subcutaneous injectable rescue therapy for ‘off’ periods in PD that was approved in the United States in 2004. We will discuss its history, chemistry and clinical use. We will also cover the recent development and approval of sublingual apomorphine film that offers a novel formulation and provides effective treatment for ‘off’ episodes including results of the phase 3 randomized, double-blinded, placebo-controlled study. Oral mucosal side effects, which were mild to moderate and reversible in most patients experiencing them, will be discussed.

Expert opinion: The new sublingual apomorphine is safe and effective for relief of ‘off’ periods that impact quality of life. Its ease of use will be beneficial to those with needle phobia and device challenges with currently available injectable and inhaled therapeutics. Side effect profile is an improvement from previous attempts at sublingual formulation.

KEYWORDS:

• Apomorphine hydrochloride
• motor fluctuations
• off times
• Parkinson’s disease

Article highlights

• Apomorphine is a crystalline aporphine alkaloid that stimulates dopamine receptors and easily crosses the blood brain barrier but is ineffective when taken orally due to high first pass metabolism.

• Subcutaneous injection of apomorphine was first approved in the United States in 2004 for on-demand treatment of ‘off’ episodes in Parkinson’s disease.

• Subcutaneous injection of apomorphine has been limited in use due to difficulty with injection mechanisms, side effects, and needle phobia.

• A phase 3 randomized, double blinded, placebo-controlled study of sublingual apomorphine demonstrated a significant reduction in MDS-UPDRS part III when given to Parkinson’s patients in an ‘off’ state when compared to placebo.

• Sublingual apomorphine produced a full ‘on’ state following 79% of doses.

• Effects last at least 48 weeks

• The most common side effect of sublingual apomorphine are mild-to-moderate oropharyngeal events.

• Sublingual apomorphine was approved in the United States in May of 2020 and is available in doses of 10, 15, 20, 25, and 30 mg.

• Sublingual apomorphine provides a novel, safe, effective and easy to use on-demand therapy for ‘off’ periods and motor fluctuations in Parkinson’s disease.

Declaration of interest

SA Factor has received honoraria from Lundbeck, Sunovion, Biogen, Acadia, Impel, Acorda, CereSpir. They have received grants from Medtronics, Boston Scientific, Biohaven, Impax, Lilly, US World Meds, Sunovion Therapeutics, Vaccinex, Voyager, Jazz Pharmaceuticals, CHDI Foundation, Michael J. Fox Foundation, NIH(U10 NS077366) and Parkinson Foundation. Finally, they have received royalties from Demos, Blackwell Futura, Springer for textbooks, Uptodate, Other Bracket Global LLC, CNS Ratings LLC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

CY Caughman is supported by the Edmond J. Safra Fellowship through the Michael J Fox Foundation. SA Factor is supported by the Sartain Lanier Family Foundation.