PHILADELPHIA -
The 2-hour improvement was considered clinically meaningful, although the average patient in the studies had about 6 hours of off-time, said investigator Peter LeWitt, MD, of Henry Ford Hospital in West Bloomfield, Mich., and the department of neurology at Wayne State University, Detroit. Dr. LeWitt and colleagues will present the data at the annual meeting of the American Academy of Neurology.
“While this is a substantial improvement, it is 2 hours improvement over a total of 6 hours of off-time, which is not perfect,” Dr. LeWitt said in an interview. “So how could we do better is the challenge for all of us who are doing research.”
Opicapone is under development in the United States; it is currently approved in the European Union as adjunctive therapy to preparations of levodopa/DOPA decarboxylase inhibitors for patients with Parkinson’s disease and end-of-dose motor fluctuations.
The ability of opicapone to prolong the clinical actions of levodopa has been evaluated in BIPARK-1 and BIPARK-2. These two international phase 3 studies evaluated the third-generation COMT inhibitor against placebo and, in the case of BIPARK-1, against the COMT inhibitor entacapone as an active control. Each study was 14-15 weeks in duration and included a 1-year open-label phase.
In BIPARK-1, on-time without troublesome dyskinesia was significantly increased for opicapone 50 mg versus placebo, with an absolute increase of 1.9 versus 0.9 hours, respectively, from baseline to week 14 or 15 (P = .002), investigators said. Similarly, BIPARK-2 data showed an increase in this endpoint, at 1.7 versus 0.9 hours for opicapone and placebo, respectively (P = .025).
The 50-mg dose of opicapone was received by 115 patients in BIPARK-1 and 147 patients in BIPARK-2, while placebo was received by 120 and 135 patients in those two studies, respectively.
In the long-term extension studies, the mean change in on-time without dyskinesia from baseline to the end of the open-label endpoint was 2.0 hours for all 494 opicapone-treated patients in BIPARK-1 and 1.8 hours for all 339 opicapone-treated patients in BIPARK-2.
Dyskinesia was reported as a treatment-emergent adverse effect for 17.4% of opicapone-treated patients and 6.2% of placebo-treated patients, according to results of a pooled safety analysis of BIPARK-1 and BIPARK-2. However, only 1.9% of opicapone-treated patients and 0.4% of placebo-treated patients had treatment-emergent dyskinesia leading to discontinuation, and the dyskinesia was considered serious in 0.3% of the opicapone group and 0.0% of the placebo group, investigators added.
Neurocrine Biosciences has announced plans to file a New Drug Application for opicapone for Parkinson’s disease in the United States. That filing is expected to take place in the second quarter of 2019, according to an April 29 press release.
Dr. LeWitt disclosed that he has served as an advisor to Neurocrine Biosciences. He also provided disclosures related to Acadia, Acorda, Adamas, BioElectron Technology, Biotie, Britannia, Intec, Jazz Pharmaceuticals, Lundbeck, the Michael J. Fox Foundation for Parkinson’s Research, Merz, NeuroDerm, the Parkinson Study Group, Pfizer, Prexton, Sage, Scion, Sunovion, SynAgile, and US WorldMeds.
SOURCE: LeWitt P et al. AAN 2019, Abstract S4.003.