The US Food and Drug Administration (FDA) has approved apomorphine hydrochloride sublingual film (Kynmobi, Sunovion) for the acute, intermittent treatment of ‘off’ episodes in patients with Parkinson’s disease (PD), the manufacturer has announced.
This marks the first approval for a sublingual therapy for this indication, which is defined as the re-emergence or worsening of PD symptoms that have otherwise been controlled with standard care of levodopa/carbidopa, Sunovion reports. Almost 60% of patients with PD experience off episodes.
Today’s approval “affords healthcare providers with a needed option that can be added to their patients’ medication regimen to adequately address off episodes as their Parkinson’s disease progresses,” Stewart Factor, DO, professor of neurology and director of the Movement Disorders Program at Emory University School of Medicine, Atlanta, Georgia, said in a press release from the manufacturer.
“We know from our research and discussion with the Parkinson’s community that off episodes can significantly disrupt a patient’s daily life,” Todd Sherer, PhD, CEO of the Michael J. Fox Foundation for Parkinson’s Research, said in the same release.
He added that the Fox Foundation “supported early clinical development of sublingual apomorphine.”
The treatment is expected to be available in US pharmacies in September.
Off episodes can include periods of tremor, slowed movement, and stiffness and occur during daytime hours.
“Several years after a person is diagnosed with [PD] they may notice problems such as having trouble getting out of bed in the morning or having difficulty getting out of a chair, or that they feel frozen while trying to walk as the effect of their maintenance medication diminishes,” Factor noted.
Apomorphine hydrochloride sublingual film is a novel formulation of apomorphine. It dissolves under the tongue to help improve off episode symptoms as needed up to five times per day.
A phase 3 study of 109 patients that was published in December in Lancet Neurology showed that those who received the sublingual film therapy had a mean reduction of 11.1 points on the Movement Disorder Society Unified PD Rating Scale Part III 30 minutes after dosing at the 12-week assessment. This was a significant improvement in motor symptoms vs those who received placebo (mean difference, -7.6 points; P = .0002).
In addition, initial clinical improvement was found 15 minutes after dosing.
The most frequently reported treatment-emergent adverse events in the study population were oropharyngeal reactions, followed by nausea, somnolence, and dizziness.
“The availability of this new apomorphine sublingual formulation, along with an inhaled formulation under development, will broaden the treatment options for off periods,” Angelo Antonini from University of Padua, Padua, Italy, wrote in an accompanying editorial in Lancet Neurology.
Although the results were encouraging, he noted some caution should be heeded.
Because of “the high rate of oropharyngeal adverse events, long-term safety needs to be monitored once the product is registered and available for chronic use in patients with Parkinson’s disease,” Antonini writes.
Other safety information issued by the manufacturer includes a warning that patients who take the 5HT3 antagonists ondansetron, dolasetron, palonosetron, granisetron, or alosetron for nausea should not also use apomorphine hydrochloride sublingual film.
“People taking ondansetron together with apomorphine, the active ingredient in Kynmobi, have had very low blood pressure and lost consciousness or ‘blacked out,’ ” the warning notes.
It also should not be taken by individuals who are allergic to the ingredients in the medication, including sodium metabisulfite.
Follow Deborah Brauser on Twitter: @MedscapeDeb .