Opicapone Improves ON, OFF Time in Levodopa-Treated Patients With Parkinson Disease

Joaquim J. Ferreira, MD, PhD

Data from an exploratory post-hoc analysis of the BIPARK I and II trials (NCT01568073 and NCT01227655) suggest that 50-mg opicapone (Ongentys; Neurocrine Biosciences) is a viable option as a first-line adjunctive treatment for patients with Parkinson disease treated with levodopa who experience motor fluctuations.¹

The assessment included 68 patients given the once-daily, oral, selective catechol-O-methyltransferase (COMT) inhibitor and 59 administered placebo, all of whom were only treated with levodopa. In total, the changes from baseline in absolute OFF and ON time were significantly greater for the opicapone group (OFF time P = .0161; ON time P = .0049).

The data were compiled by Joaquim J. Ferreira, MD, PhD, faculty of medicine, University of Lisbon, and colleagues, and presented in a poster at the 2020 MDS Virtual Congress, September 12–16, 2020.

“Levodopa still remains the most effective symptomatic treatment for Parkinson’s disease,” Ferreira and colleagues wrote, noting that post oral administration of levodopa, the drug is extensively metabolized in the periphery by dopa decarboxylase and COMT, opening a window for opicapone to fill that need.

At baseline, the mean daily OFF time reported by patients was 6.6 hours (standard deviation [SD], 2.3) for both groups, with the opicapone and placebo groups reporting an average of 2.4 years (SD, 2.6) and 1.8 years (SD, 1.4) of duration of motor fluctuations. The baseline daily ON time with troublesome dyskinesia was 0.5 hours (SD, 1.4) for the opicapone group and 0.5 hours (SD, 1.2) for the placebo group. Mean daily levodopa doses were 730.3 mg (SD, 347) and 718.3 mg (SD, 359.1) for the opicapone and placebo groups, respectively.

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The least-squares mean reduction from baseline in absolute OFF time was 109.2 minutes (95% CI, –147.9 to –70.4) for the opicapone group compared to 40.3 minutes (95% CI, –80.7 to 0) for the placebo group, an absolute difference of 68.8 minutes (95% CI, –124.8 to –12.8).

Similarly, the least-squares mean increase in absolute ON time from baseline was 96.7 minutes (95% CI, 58.1–135.3) for the opicapone group, while the placebo group experienced a gain of 16.9 minutes (95% CI, –23.3 to 57.0). The absolute difference between groups was 79.8 minutes (95% CI, 24.3–135.4).

The safety data set revealed that the overall incidence of adverse events (AEs) possibly related to treatment was higher for the opicapone group (44.1%; n = 30) compared to placebo (22%; n = 13), though the incidence of these AEs that led to treatment discontinuation was comparable for the groups (opicapone: 7.4% [n = 5]; placebo: 8.5% [n 5]). No more than 1 patient in each group reported any serious AEs possibly related to treatment. The placebo group reported 1 patient with a cognitive disorder, acute hepatitis, and acute pancreatitis; while the opicapone group had 1 patient with dyskinesia.

Opicapone was FDA-approved for add-on treatment in April 2020, and just this week, 50-mg capsules of opicapone became available by prescription in the United States.² The agency granted the approval based on the BIPARK trials, which included approximately 1000 patients with Parkinson disease compared with placebo and the active comparator drug entacapone (Comtan; Novartis). Participants were randomly assigned to 1 of 3 doses of the study drug (5 mg, 25 mg, or 50 mg), placebo, or the active comparator for 14 or 15 weeks.

BIPARK I results revealed a placebo-adjusted OFF time reduction of 60.8 minutes in the 50-mg group, a 51% greater reduction than what was observed in the active comparator group (40.3 minutes).³ In the open-label extension study, patients who switched from placebo or entacapone experienced a 65-minute and 39-minute decrease in mean OFF time. Notably, ON time without dyskinesia increased by 43 minutes and 46 minutes, respectively.⁴

In BIPARK-2, opicapone demonstrated a significant 54.3-minute reduction in OFF time versus placebo in the 50-mg group, with daily off time reduced by 126.3 minutes over 1-year follow-up.⁵

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REFERENCES
1. Ferreira J, Poewe W, Antonini A, et al. Opicapone as First-Line Adjunctive Levodopa Treatment in Parkinson's Disease Patients with Motor Fluctuations: Findings from BIPARK-I and II Combined Post-Hoc Analysis. Presented at: MDS Virtual Congress; September 12–16, 2020. Abstract 999.
2. Neurocrine Biosciences Announces Once-Daily ONGENTYS® (opicapone) Now Available in the U.S. as an Add-On Treatment for Patients with Parkinson's Disease Experiencing "Off" Episodes. News release. San Diego, CA. Neurocrine Biosciences. Published September 14, 2020. Accessed September 14, 2020. https://www.biospace.com/article/releases/neurocrine-biosciences-announces-once-daily-ongentys-opicapone-now-available-in-the-u-s-as-an-add-on-treatment-for-patients-with-parkinson-s-disease-experiencing-and-quot-off-and-quot-episodes
3. Ferreira J, Lees A, Rocha J-F, et al. Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol. 2016;15(2):154-165. doi: 10.1016/S1474-4422(15)00336-1
4. Ferreira J, Lees A, Tolosa E, et al. Switch of Double-Blind Opicapone, Entacapone, or Placebo to Open-Label Opicapone: Efficacy Results of the 1-year Extension of Study BIPARK I. Presented at: IAPRD. Lyon, France; August 19-22. Accessed July 10, 2019.
5. Lees AJ, Ferreira JJ, Rascol O, et al. Opicapone as adjunct to levodopa therapy in patients with Parkinson disease and motor fluctuations: a randomized clinical trial. JAMA Neurol. 2017;74(2):197-206.