New Data Support Effectiveness of Ongentys for Parkinson’s ‘Off’ Periods

Ongentys (opicapone) can reduce the extent of “off” periods in people with Parkinson’s disease being treated with  levodopa, new clinical trial data show.

The data were presented at the American Neurological Association 2020 Virtual Meeting.

Therapies that aim to increase levels of dopamine in the brain, such as levodopa and carbidopa, are mainstays of Parkinson’s treatment. While these therapies can reduce the symptoms of Parkinson’s disease, they tend to become less effective over time. This leads to the development of “off” periods, where symptoms are not controlled effectively.

“As Parkinson’s disease progresses and the benefit of treatment with levodopa/carbidopa begins to wear off between doses, many patients experience increased fluctuation and unpredictability in their motor function, which can include more ‘off’ time overnight and during the day, and a reduction in good ‘on’ time where movement is close to normal,” Eiry W. Roberts, MD, said in a press release. Roberts is chief medical officer at Neurocrine Biosciences, which markets Ongentys.

Ongentys is a COMT (catechol-o-methyl transferase) inhibitor, a medication that blocks the activity of enzymes that normally break down levodopa, thereby extending the effect of the medication in the body. Ongentys has been approved as an add-on treatment for “off” periods in Parkinson’s disease in the U.S., the European Union, and Japan.

The safety and effectiveness of Ongentys has been demonstrated in many clinical trials, including two multinational Phase 3 trials: BIPARK-1 (NCT01568073) and BIPARK-2 (NCT01227655). The new findings come from post-hoc analyses of these trials (analyses done after the trial has already been completed).

In one presentation, “Efficacy of Opicapone at Different Levodopa Regimens up to a Threshold of 600mg/Day Levodopa in Parkinson’s Disease Patients with Motor Fluctuations,” (page S187), researchers from Neurocrine and elsewhere combined efficacy data from both Phase 3 trials, analyzing a total of 121 people who had been treated with Ongentys (at 50 mg/day) and 118 who had been given placebo — both in addition to levodopa.

At all levodopa doses analyzed, individuals treated with Ongentys had a significantly greater reduction in the time they spent in “off” periods. On average, Ongentys-treated participants had more than an hour-and-a-half less “off” time after starting treatment. In comparison, those given placebo reported less than an hour decrease in “off” time, on average.

“[Ongentys] showed a similar magnitude of effect between different low levodopa dose regimens, with at least a two-fold greater OFF-time reduction than placebo,” the researchers concluded.

In a separate presentation, “Effect of Opicapone and Entacapone on Early Morning-OFF Pattern in Parkinson’s Disease Patients with Motor Fluctuations,” (page S182) researchers assessed data for 235 participants in BIPARK-1 who were treated with either Ongentys or Comtan (entacapone), another COMT inhibitor produced by Orion and marketed by Novartis in the U.S.

At the beginning of the study, less than 15% of patients woke up in an “on” status, meaning their symptoms were adequately controlled.

Using data from diaries the participants filled out during the trial, the researchers found that by the end of the study the proportion of patients who woke up in an “on” status increased by 12.2% in those treated with Ongentys, compared to 7.5% for those treated with Comtan.

Additionally, the time to the first “on” period, after the first dose of levodopa for the day, decreased by an average of 17.7% with Ongentys, as compared to a decrease of 1.9% for Comtan.

Of note, early morning “off” patterns were observed in some individuals on Comtan, but not in those on Ongentys. The reduction in morning “off” time was twice as large among those treated with Ongentys (20% vs. 10%).

“Treatment with opicapone 50 mg, in comparison with entacapone, led to a greater increase in the proportion of patients who woke up in ON-status and a greater decrease in time-to-ON from first morning levodopa intake,” the researchers concluded.

“These post-hoc analyses from the Phase 3 clinical trials of Ongentys provide further insight on how adding once-daily Ongentys to levodopa/carbidopa can help patients with Parkinson’s disease better manage disruptive motor fluctuations over the course of the day,” Roberts said.