Opicapone Shows Motor Benefits, Eases ‘Off’ Periods for Parkinson’s Patients in Phase 3 Study

Once-daily treatment with opicapone provides continued reductions of off periods in Parkinson’s patients taking levodopa, a Phase 3 clinical study shows.

The findings also reveal that opicapone’s effectiveness was superior to that of Comtan (entacapone, marketed by Novartis).

The results were presented in three scientific posters at the 2018 World Congress on Parkinson’s Disease and Related Disorders (IAPRD), taking place in Lyon, France.

Opicapone, developed by Bial and Neurocrine Biosciences, is designed as a once-daily add-on therapy to levodopa for adults with Parkinson’s and end-of-dose motor fluctuations. It is an inhibitor of the enzyme catechol-o-methyltransferase, or COMT, which breaks down levodopa. This leads to prolonged levodopa effects, as it reduces the time when the medication wears off before the next dose — s0-called off periods.

It is currently marketed in Europe as Ongentys. The company is intending to start the U.S. regulatory review in early 2019, which could lead to the medication’s approval.

“Neurocrine Biosciences is committed to bringing innovative and effective treatments to patients living with movement disorders,” Eiry W. Roberts, MD, Neurocrine’s chief medical officer, said in a press release. Roberts added that these findings will help healthcare providers further understand “the potential of opicapone to help [Parkinson’s] patients.”

Bial compared the effectiveness and safety of 5, 25 and 50 mg doses of opicapone over a three-week treatment to that of 200 mg of Comtan (also a COMT inhibitor) and placebo. Primary results from BIPARK I as well as data from its open-label extension phase already had been published.

The multi-center, double-blind Phase 3 study (NCT01568073) included patients 30 to 83 years old, with a three-year diagnosis of idiopathic Parkinson’s, Hoehn and Yahr (H-Y) stage — a system used to assess the worsening of Parkinson’s symptoms — of 1 to 3 (meaning minimal or no functional disability, to mild-to-moderate disability), and receiving treatment with levodopa for at least one year.

In the study, “Efficacy of Opicapone in Parkinson’s Disease Patients with Motor Fluctuations: A Phase III, Randomized, Double-Blind, Placebo- and Active-Controlled Study – BIPARK I,” researchers analyzed data from 590 patients — 119 taking 5 mg of opicapone, 116 receiving 25 mg, 115 taking 50 mg, 120 on 200 mg Comtan, and 120 on placebo.

Results showed that both 50 mg opicapone and Comtan significantly decreased the duration of daily off periods and increased “on time” (periods when symptoms are controlled) without troublesome dyskinesia, which are involuntary, jerky movements. However, the higher dose of opicapone led to a 51% greater reduction in off periods (50.8 minutes vs. 40.3 minutes).

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The data further revealed that, unlike Comtan, 50 mg opicapone was associated with significant improvement in the proportion of both off and on responders (minimum of one hour improvement) compared to placebo. Also, unlike Comtan and placebo, opicapone led to favorable ratings in both Patient Global Impression of Change (PGI-C) and Clinical Global Impression of Change (CGI-C).

This was further addressed in the study, “Opicapone as Adjunctive Therapy to Levodopa in Patients with Parkinson’s Disease and Motor Fluctuations: Global Impressions of Change Compared to Placebo and Entacapone,” which reported that, for PGI-C, the proportion of patients reporting improvement ranged between 63.8% to 72.2% for opicapone groups, vs. 50.8% for placebo, and 52.5% for Comtan.

As for CGI-C, the proportion of patients assessed as improved ranged between 60.3% to 73.0% for opicapone, in comparison to 50.0% for placebo and 50.8% for Comtan.

Treatment-emergent adverse events (TEAEs) were reported by 51.6%-54.6% of patients taking opicapone, 56.6% on Comtan, and 49.6% on placebo.

Compared to placebo, opicapone led to more common dyskinesia, insomnia, and dizziness. TEAEs were similar between opicapone and Comtan.

“[Opicapone] 50 mg once-daily was effective in the treatment of motor fluctuations with a favorable profile compared to [Comtan],” researchers wrote.

The study, “Switch of Double-Blind Opicapone, Entacapone, or Placebo to Open-Label Opicapone: Efficacy Results of the 1-Year Extension of Study BIPARK I,” reported the efficacy results of a one-year extension study of BIPARK I. This trial included patients who completed BIPARK I or the Phase 3 study BIPARK II (NCT01227655).

All patients included in study began with a 25 mg dose of opicapone for a minimum of one week, regardless of prior double-blind treatment.

Compared to the start of the trial (baseline), mean off time was reduced by 34 minutes. If comparing to the start of BIPARK I, this represented a decrease superior to two hours (127 minutes).

Opicapone reduced off periods by 65 minutes and 39 minutes and increased on periods without troublesome dyskinesia by 43 minutes and 46 minutes, when compared to BIPARK I participants’ taking placebo or Comtan, respectively.

Overall, opicapone “maintained its efficacy over the 1-year treatment period,” researchers wrote.

The medication was originally developed by Portugal-based BIAL, which licensed the North American rights to Neurocrine in February 2017.