Opicapone Maintains Efficacy in Parkinson Disease in Open-Label Extension

Eiry Roberts, MD, the chief medical officer at Neurocrine Biosciences

Eiry Roberts, MD

Opicapone has been shown to significantly reduce off time in patients with Parkinson disease who switched to the therapy from entacapone, while also increasing on time without dyskinesia.

In data from a 1-year, open-label extension from the BIPARK I trial, the novel, once-daily, peripherally-acting, selective catechol-o-methyltransferase (COMT) inhibitor not only maintained its efficacy over 1 year but also resulted in 65-minute (P <.0001) and 39-minute (P = .0060) decreases in mean off time for patients who switched from placebo (n = 81) and entacapone (n = 87), respectively. Additionally, on time without dyskinesia increased for those patients by 43 minutes (P = .0247) and 46 minutes (P = .0148), respectively.¹

“The one-year extension study of BIPARK-I adds to the clinical trial data evaluating opicapone as a potential adjunct treatment for Parkinson’s disease,” Eiry Roberts, MD, the chief medical officer at Neurocrine Biosciences, the product’s developer, told NeurologyLive. “Specifically, the extension study compared adjunctive treatment with opicapone to entacapone, a first generation COMT inhibitor and one of the most commonly used COMT inhibitors. The data showed that switching from adjunctive treatment with entacapone to opicapone resulted in a statistically significant decrease of OFF-time and an increase of ON-time without troublesome dyskinesia.”

The extension study results were presented at the International Association of Parkinsonism and Related Disorders (IAPRD), in Lyon, France. The extension period included 495 of the original 542 patients that completed the double-blind phase, with 432 (87.3%) completing the extension. Patients were started in the open-label phase on 25-mg opicapone, once daily for 7 days, after which the levodopa dose was adjusted first, then the opicapone dose would be titrated down if unacceptable dopaminergic treatment-emergent adverse events (AE) occurred.

For those who continued opicapone from the 5-mg dose (n = 88), the mean off-time change from the double-blind baseline to the open-label endpoint was -27.5 minutes (95% CI, -55.7 to 0.6). Meanwhile, those who continued from the 25-mg dose (n = 89) and the 50-mg dose (n = 84), there were mean off-time reductions of 23.0 minutes (95% CI, -51.3 to 5.2) and 1.8 minutes (95% CI, -30.5 to 26.9).

Likewise, all 5 groups experienced increases in on time without dyskinesia. Those who continued opicapone observed increases of 5.6 minutes (95% CI, -31.1 to 42.2), 25.9 minutes (95% CI, -10.9 to 62.6), and 21.1 minutes (95% CI, -16.2 to 58.4), for the original 5-mg, 25-mg, and 50-mg patients, respectively.

“Parkinson’s disease is a debilitating and progressive disease that affects nearly 1 million Americans and has no present cure,” Roberts said. “While levodopa is effective in controlling the motor symptoms, as the disease progresses, the beneficial effects of levodopa begin to wear off and patient symptoms worsen. We are excited about the Phase III opicapone data as the results demonstrate the potential of opicapone to be an effective and well-tolerated adjunct treatment for Parkinson’s disease patients in the US, especially when compared to adjunct treatments currently on the market.”

The original BIPARK I trial, originally published in The Lancet Neurology, evaluated the efficacy and safety of opicapone in 5-mg (n = 119), 25-mg (n = 116), and 50-mg (n = 115) doses compared to entacapone 200 mg (n = 120) and placebo (n = 120) in 590 patients with Parkinson disease.² The trial revealed a placebo-adjusted off time reduction for the 50-mg group of 60.8 minutes—a 51% greater decrease than the 40.3-minute reduction observed with entacapone.

“There are other COMT inhibitors that are currently available, but they have been limited in their use due to pill burden, modest effect, tolerability issues and safety risks,” Roberts explained. “People living with Parkinson’s disease are already burdened by their treatment regimen, so we are excited about the potential of opicapone as a once-daily treatment option for patients that has demonstrated improvement in motor fluctuations and a favorable risk-benefit profile in Phase III studies.”

REFERENCES

1. 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 August 23, 2018.

2. 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. 2016; 15(2): 154-165.

doi

: 10.1016/S1474-4422(15)00336-1.