FDA Accepts Resubmitted New Drug Application for APL-130277 Apomorphine Film, Sunovion Announces

The U.S. Food and Drug Administration has accepted Sunovion‘s resubmitted new drug application (NDA) for APL-130277, an oral apomorphine therapy for treating off episodes in Parkinson’s disease.

The FDA had asked for additional information regarding APL-130277, following the first NDA in mid-2018. A response to this resubmission is expected by May 21.

APL-130277 is an under-the-tongue (sublingual) apomorphine film that may be easier for patients to take. The therapy is intended to provide on-demand and fast-acting lessening of all types of off episodes: periods of worsening symptoms that typically occur between the loss of a medication’s effect and when the next dose can be taken. These symptoms include tremors, rigidity, and slowness, as well as cognitive impairment and mood disorders.

Some 40% to 60% of those with Parkinson’s experience off episodes, which grow worse and more unpredictable over time.

“The unpredictable nature of off episodes can be extremely challenging and disruptive to the daily lives of people living with Parkinson’s disease as well as their care partners,” Antony Loebel, MD, president and CEO of Sunovion, said in a press release.

“We look forward to working with the FDA over the remaining review period,” Loebel added.

The agency had requested additional information — but no new clinical trials — before deciding whether to approve APL-130277. The new submission included additional analysis of clinical data, and information about the intended packaging of APL-130277, according to Sunovion.

Apomorphine crosses the blood-brain barrier — a network of blood vessels that allows the entry of essential nutrients to the brain while blocking potentially harmful substances and also some therapies — to stimulate dopamine production in the brain. Parkinson’s is biologically characterized by the loss of dopamine-producing (dopaminergic) neurons.

Other apomorphine medications, such as Apokyn, must be assembled and injected, which can pose a challenge for people with Parkinson’s. A common side effect to these medications is nausea, for which patients also must take an antiemetic.

In contrast, APL-130277 easily absorbs through the skin under the tongue and clinical trial participants reportedly tolerated it well without severe nausea. David Blum, MD, Sunovion’s global head of neurobiology, attributes this tolerance to a slower drop in the concentration of APL-130277 in patients’ blood, as compared with Apokyn. In past reporting, Blum has suggested that the sharp drop in blood Apokyn concentration may contribute to feelings of nausea. APL-130277, conversely, is absorbed quickly, but leaves the system in a slower, steadier fashion.

The treatment was seen in a Phase 3 clinical trial (NCT02469090) to ease the motor fluctuations associated with off episodes. During the study, participants received increasing doses of the compound over a 12-week period. Roughly two-thirds of 109 patients completed the trial. APL-130277 treated up to 5 off episodes throughout a given day. Some mild-to-moderate side effects, but none severe, were reported. Those reported included transient nausea, drowsiness, and dizziness.

Sunovion continues to recruit patients for an open-label extension study (NCT02542696) investigating the long-term safety and efficacy of APL-130277. Recruitment is open in Los Angeles and several European locations. More information can be found here.

If approved by the FDA, APL-130277 would join Inbrija, a levodopa inhalation powder from Acorda Therapeutics’, as one of a scant few treatments for off episodes. The Michael J. Fox Foundation helped fund early development of both compounds.