FDA Accepts New Drug Application for Opicapone as Add-on Therapy

The U.S. Food and Drug Administration has accepted Neurocrine Biosciences’ new drug application for opicapone as a potential add-on therapy to levodopa/carbidopa for Parkinson’s disease.

The FDA has set a 12-month review process, with a decision expected by April 26, 2020. If approved, the FDA will start its Prescription Drug User Fee Act (PDUFA), which authorizes the agency to collect fees from companies that produce certain human therapies and biological products. Since the passage of PDUFA, user fees have played an important role in expediting therapies’ approval process.

Opicapone, developed by Bial and Neurocrine Biosciences, is an oral, once-per-day add-on therapy to levodopa for adults with Parkinson’s, and end-of-dose motor fluctuations.

Levodopa is considered the gold-standard treatment for Parkinson’s. However, its long-term use is linked with end-of-dose, or wearing-off fluctuations, leading to progressively shorter intervals in which symptoms are adequately controlled.

Opicapone works by blocking the enzyme catechol-o-methyltransferase, or COMT, which breaks down levodopa. This can prolong levodopa effects, known as “on-time” or “on-periods.”

The therapy was approved in Europe for Parkinson’s patients with fluctuations that cannot be treated with lepodova or combinations of similar therapies, and whose motor symptoms re-emerge before the next dose is due. It is marketed by Bial in Europe under the brand name Ongentys. Neurocrine holds the rights for opicapone in North America.

Data from over 30 clinical trials, including two Phase 3 trials, BIPARK-1 (NCT01568073) and BIPARK-2 (NCT01227655), support opicapone’s clinical benefits. The trials enrolled more than 900 Parkinson’s patients who could not effectively control their motor symptoms with standard therapies.

In the BIPARK-1 study, participants were randomly selected to receive 5, 25, or 50 mg daily doses of opicapone, plus either levodopa or Comtan (entacapone, marketed by Novartis), or a placebo. In BIPARK-2, opicapone was given as an add-on to either levodopa or placebo. Treatment was maintained for 14 to 15 weeks, after which participants had the opportunity to continue opicapone add-on therapy for more than one year in an open-label extension study.

Data from the BIPARK-1 trial showed that people treated with 50 mg opicapone had twice longer on-time periods without dyskinesia, or involuntary movements, compared with those receiving placebo (controls).

The BIPARK-2 study showed similar results. Participants taking 50 mg of opicapone had 1.7 hours of absolute on-time without dyskinesia compared with 0.9 hours in the placebo group.

The on-time periods were maintained in long-term extension studies for all opicapone-treated patients, with increases of 2 hours in the BIPARK-1 study, and 1.8 hours in the BIPARK-2 trial.

“People living with Parkinson’s disease often struggle to control their motor fluctuations due to the progressive neurodegenerative effects of the disorder. With opicapone, we aim to prolong the benefits of levodopa by providing a new treatment option to patients with Parkinson’s disease in the U.S.,” Eiry W. Roberts, MD, Neurocrine’s chief medical officer, said in a press release.

“It is our goal to help patients maintain good ON time — the period when their motor symptoms are better controlled — and reduce OFF time — the period when the effects of levodopa have worn off. We look forward to working with the FDA to bring this new treatment option to patients coping with this debilitating disorder,” Roberts added.