Sunovion Expects APL-130277 Will Ably Treat Off Episodes, Awaits FDA Decision

If the FDA approves Sunovion’s APL-130277 come January, Parkinson’s patients will have a first oral treatment — and a first new treatment in more than a decade — for off episodes, those times of difficulties with movement despite taking dopamine agonists like lepodova.
“We think that for the first time, we may have a product that can be used in a manner that is really effective, accessible, and helpful for patients who suffer from off episodes,” Antony Loebel, MD, Sunovion’s chief medical officer, told Parkinson’s News Today. The U.S. Food and Drug Administration accepted the company’s request to approve APL-130277 in June, and set Jan. 29 as a decision date.
Antony Loebel, Sunovion’s chief medical officer. (Photos courtesy of Sunovion)
Off episodes, or motor fluctuations, can come in a variety of forms. All affect a Parkinson’s disease patient’s ability to move voluntarily or cause unwanted movement (dyskinesia).
Some involve waking “up early in the morning and be frozen and not able to get out of bed until their morning dose kicks in, which can be in an hour. There are off episodes as the dose wears off,” said David Blum, MD, global head of neurology clinical research at Sunovion. “And there are more unpredictable off episodes that happen because of the internal bizarre nature of dopamine agonists like levodopa for Parkinson’s — erratic off episodes [and] delayed-on, where a patient takes a drug but it doesn’t act for a long time.”
About 40 to 50 percent of all patients experience off episodes, which generally become more severe and less predictable as the disease advances.
Parkinson’s is caused by the progressive loss of neurons that release a neurotransmitter, called dopamine, in the substantia nigra, a part of the brain that controls movement. Levodopa, an oral medication that is absorbed through a patient’s gastrointestinal tract and transported to the brain — where it is converted into dopamine — is considered the gold standard of Parkinson’s treatment.
Levodopa (combined with benserazide or carbidopa in a capsule or tablet) doesn’t stop or slow neuronal death. But it treats some of the disease’s most common symptoms, such as tremors and stiffness, by temporarily making more dopamine available.
Over time and with longer use, a patient’s response to levodopa diminishes and off periods become more frequent.
APL-130277 (apomorphine sublingual film) is not the only treatment targeting these episodes, but it may be more convenient and effective than Apokyn (apomorphine hydrochloride, US WorldMeds), approved in 2004.
Most off periods last 60 to 90 minutes, so any treatment needs to be fast-acting. Apomorphine — the active ingredient in both Apokyn and APL-130277 — can penetrate the brain quickly and stimulate dopamine receptors to provide short-term, levodopa-like relief. But it’s not easily absorbed when taken orally.
“If you deliver it in a way that bypasses oral absorption,” Blum said, “you can get a rapid rise in apomorphine levels … which kicks the patient from the off state to the on-state.”
David Blum, global head of clinical neurology at Sunovion.
Apokyn needs to be assembled and injected under the skin. Blum notes this can be a challenge for patients with movement disorders and their caregivers.
APL-130277 is a quick-acting sublingual treatment. Patients

Source: Parkinson's News Today

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