After a protocol adjustment that disallowed the use of the antiemetic trimethobenzamide during dose-titration, adverse event data from an open-label study of apomorphine sublingual film (Kynmobi; Sunovion) suggest antinausea treatment might not be necessary.
After an adjustment to the protocol of an ongoing, multicenter, open-label phase 3 study (NCT02542696) of the use of apomorphine sublingual film (Kynmobi; Sunovion) in the treatment of patients with Parkinson disease (PD), no more than 13% of those enrolled at that point who were unable to utilize the antiemetic trimethobenzamide during the dose-titration phase reported experiencing vomiting, nausea, or treatment-emergent adverse events (AEs) associated with either.1
This analysis included a data cut in September 2020, which included 176 new patients enrolled post protocol amendment. Of those, 145 did not receive trimethobenzamide as an antiemetic treatment. These patients received doses of apomorphine sublingual film of 10 mg to 30 mg. Notably, 76% of these patients received the highest dose of the therapy within their first 3 doses.
“The majority of United States patients with Parkinson’s disease and ‘OFF’ episodes were titrated to an effective and tolerable dose of apomorphine sublingual film without antiemetics in an interim analysis of a long-term safety and efficacy study after a protocol amendment that prohibited prophylactic use of trimethobenzamide,” investigators, including Robert A. Hauser, MD, MBA, professor of neurology, and director, Parkinson’s Disease and Movement Disorder Center, University of South Florida, wrote.
During the dose-titration phase, the highest dose received was 10 mg for 29% of patients, 15 mg for 26%, 20 mg for 22%, and 25 mg for 16%. Hauser and colleagues presented the data in a poster at the 2022 Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress in Washington, DC, June 17-19.
Among those who did not receive trimethobenzamide, nausea was reported in 13% of patients, which was mostly mild (74%) or moderate (26%), with no patients reporting severe nausea nor discontinuing because of it. Vomiting was only reported by 1% of this group, being mild in nature and not resulting in discontinuation.
Those who did receive trimethobenzamide during dose titration and reported these AEs also experienced them mostly at mild to moderate severity, with 6% reporting severe nausea, 25% reporting severe vomiting, and 6% reporting a severe combination of nausea and vomiting. Although 10% of the patients discontinued because of nausea and because of the combination, no patients discontinued because of vomiting alone. All told, 52% of these individuals reported nausea, 13% reporting vomiting, and 55% reporting nausea and vomiting.
“Nausea and vomiting occur with dopamine agonists, including apomorphine,” Hauser et al wrote. “Antiemetics (eg, trimethobenzamide and domperidone) have been administered prophylactically in clinical trials to prevent nausea and vomiting associated with apomorphine use. The supply of trimethobenzamide in the US is reported to be constrained.”
At the 2021 virtual International Parkinson and Movement Disorders (MDS) Society Virtual Congress, September 17-22, another author on this work, William Ondo, MD, spoke with NeurologyLive® about data on the sublingual film presented there from both the pivotal (CTH-300) and long-term studies (CTH-301), which further explored the safety, efficacy, and tolerability of the treatment. According to Ondo, who is the director of the Movements Disorders Clinic at Houston Methodist Neurological Institute, and professor of neurology at Weill Cornell Medical College, the primary difficulty associated with apomorphine is the delivery system, as the treatment is poorly absorbed orally.2,3
“The main take-home message for Kynmobi is that it's very effective—it works very, very quickly. Although there's no comparison to subcutaneous injections, it seems to be in the same ballpark as far as rapidity to onset and perhaps [with] a longer duration of benefit,” Ondo said at the time.
In December 2021, data were published by Thach et al using a cost-effectiveness model that suggested that apomorphine sublingual film is less costly and more effective on average compared with apomorphine hydrochloride (Apokyn; Supernus Pharmaceuticals) and levodopa inhalation powder (Inbrija; Acorda Therapeutics).4
Over a 10-year time period, because of higher discontinuation rates, patients in the apomorphine sublingual film group incurred slightly higher medical costs compared with apomorphine hydrochloride ($3403 vs $3363; difference, $40), while the substantially higher efficacy of apomorphine sublingual film resulted in lower incurred medical costs compared to the levodopa inhalation powder group ($3403 vs $3627; difference, $224). Furthermore, there was a range in costs related to treatment-emergent AEs, which totaled $367 for apomorphine sublingual film, $530 for apomorphine hydrochloride, and $114 for levodopa inhalation powder.4