No Need for Nausea Treatment for Most Patients on Kynmobi
The majority of Parkinson’s patients given Sunovion‘s Kynmobi (apomorphine hydrochloride) for “off” episodes during Phase 3 clinical trials did not require additional treatment for vomiting or nausea, the company said.
Indeed, an analysis found that nearly 90% of participants reached the optimal dose of Kynmobi in trials without needing antiemetics, or medicines to treat nausea and vomiting, according to a Sunovion press release.
These findings are scheduled to be presented in two posters at the International Parkinson and Movement Disorder Society (MDS) Virtual Congress 2021, to be held online Sept. 17-22.
Kynmobi is a sublingual film or under-the-tongue formulation of apomorphine that’s designed to reduce off episodes — times when symptoms reappear as a therapy wears off — in Parkinson’s patients. It can be taken up to five times a day, at doses ranging from 10 mg to 30 mg.
The therapy was approved in the U.S. in May 2020, and in Canada one month later.
Here, researchers evaluated the therapy in two trials involving Parkinson’s patients who experienced off episodes while taking stable medications for the disorder. The trials included a pivotal Phase 3 North American study (NCT02469090, CTH-300) and a long-term, open-label safety and efficacy study (NCT02542696, CTH-301).
In a first poster, titled “Apomorphine Sublingual Film for OFF Episodes in Parkinson’s Disease: Impact of Concomitant Antiemetics on Nausea and Vomiting,” researchers will report on the data obtained from a preliminary analysis of the titration phase of the open-label study (CTH-301; open-label means all patients are given active treatment) to assess whether patients require an antiemetic until they reach their optimal dose of Kynmobi.
Of note, nausea and vomiting commonly occur with dopaminergic medications such as Kynmobi.
During this phase, the participants were given increasingly higher doses (10–35 mg at 5 mg increments) of the sublingual film treatment, until they achieved complete control of their symptoms during “off” periods, which occurred within 45 minutes of taking Kynmobi.
Preventive (prophylactic) treatment with the antiemetic Tigan (trimethobenzamide) was mandatory at first but then made optional, according to the investigator’s discretion.
The analysis, with cut-off data by Sept. 30, 2020, included 176 patients treated with more than one dose of Kynmobi, of whom 31 (18%) also received trimethobenzamide (145, or 82%, did not).
Overall, the results showed that most patients — 88% in all — were successfully titrated, or incrementally increased, to the optimal dose of Kynmobi without the need for antiemetics.
A post-hoc analysis — meaning it was conducted after the data was seen — of the titration phase of the pivotal study (CTH-300) is slated to be presented at the conference in a poster titled “Apomorphine Sublingual Film for OFF Episodes in Parkinson’s Disease: Characterization of Acute Nausea During Dose Titration.”
The aim was to assess the rate of acute episodes of nausea in patients given Kynmobi for on-demand relief of off episodes. Acute episodes of nausea were defined as those that began following the administration of a single dose of Kynmobi.
Among 141 patients given Kynmobi, 29 (21%) experienced episodes of nausea during the titration phase. Of these, 22 (16%) had acute nausea episodes during clinic visits following Kynmobi’s start, while the remaining seven reported intermittent nausea outside of clinic visits and not immediately following them being given Kynmobi.
The acute episodes of nausea, however, were in general mild (in 57% of cases) and lasted less than one hour (mean of 46.2 minutes). In general, nausea occurred within a mean of 27.7 minutes after treatment with Kynmobi. Only 13% of patients reported severe nausea.
Moreover, in the majority of acute nausea cases (87%) the dose of Kynmobi did not require adjustment.
Overall, the findings suggest that “acute episodes of nausea rarely impacted patients’ ability to continue treatment,” the researchers wrote.
“These data provide a deeper understanding of the patient treatment experience and reinforce the previously-reported tolerability of Kynmobi for the on-demand treatment of PD OFF episodes,” said William G. Ondo, MD, director of the movement disorders clinic at Methodist Neurological Institute in Houston, Texas, and one of the investigators of the CTH-301 study.
“The experience of acute nausea in Kynmobi trials was largely mild in nature and rarely impacted successful titration or treatment continuity, even in the absence of antiemetic treatment,” Ondo added.
A third poster, titled “Long-Term Safety and Efficacy of Apomorphine Sublingual Film for OFF Episodes in Parkinson’s Disease: Europe vs. North America,” will present data from up to 48 weeks (nearly one year) of use of Kynmobi in European versus North American patients enrolled in the CTH-301 study.
The analysis showed that the overall incidence of treatment-emergent adverse events was similar between both groups — 81% in Europeans and 84% in North American patients.
Patients from Europe, however, experienced lower rates of nausea, dizziness, orthostatic hypotension (a form of low blood pressure), and somnolence, or sleepiness.
Kynmobi’s effectiveness was seen within 30 minutes of its administration, and it was greater in European patients, as shown by a greater decrease in the MDS-UPDRS Part III score, by 24 weeks (nearly six months) and maintained by 48 weeks. The MDS-UPDRS Part III score is a standard measure used in Parkinson’s disease, in which a decrease in scores indicate less severe symptoms.
The majority of patients across both regions (over 75%) achieved a fully “on” response within 30 minutes of taking Kynmobi through the 48 weeks.
Research on Kynmobi is being presented in five additional posters at MDS 2021. The abstracts of all posters are available here.