Ongentys Seen to Shorten Overnight ‘Off’ Periods, Lengthen Good ‘On’ Time

Oral Ongentys (opicapone) as a daily add-on treatment shortened overnight “off” periods and eased dyskinesia during “on” periods in people with Parkinson’s disease using levodopa, new analyses of Phase 3 clinical trial data show.

Long-term use was also seen to lower patients’ average daily levodopa dose without worsening symptoms of dyskinesia (involuntary movements), researchers reported.

These findings were presented at the American Neurological Association (ANA) 2020 Virtual Meeting.

Therapies such as levodopa and carbidopa are mainstays of Parkinson’s treatment, and work by increasing levels of dopamine in the brain. These medications help to ease disease symptoms, but they often become less effective over time. This leads to the development of “off” periods, times when symptoms are not controlled effectively.

Ongentys is a COMT (catechol-o-methyl transferase) inhibitor, a type of therapy that prevents the breakdown of levodopa in the body to extend its effectiveness. Marketed by Neurocrine Biosciences, Ongentys is approved as an add-on treatment to levodopa/carbidopa to address “off” periods in Parkinson’s patients in the U.S., the European Union, and Japan.

Ongentys has been evaluated in multiple clinical trials, including two multinational Phase 3 studies: BIPARK-1 (NCT01568073) and BIPARK-2 (NCT01227655). At the AAN meeting, researchers from Neurocrine and elsewhere presented several new post-hoc analyses (analyses done on a completed trial) from these studies.

In one presentation, “Effects of Once-Daily Opicapone on Duration of Overnight OFF and Time to Morning ON in Patients with Parkinson’s Disease and Motor Fluctuations” (page S189), researchers specifically evaluated the effects of Ongentys on “off” periods occurring overnight or in the early morning, using information collected from diaries kept by patients during the trials.

For both trials, the researchers compared data from 67 people using Ongentys and 48 given a placebo. Relative to the start of the trial, those on Ongentys reported a mean 52% reduction in overnight “off” time, and a 22% decrease in the time to a first “on” period in the morning (when symptoms are controlled). Among the placebo group, overnight “off” time dropped by 29%, and the time to first “on” period by 12%.

Other analyses used only data from BIPARK-1, comparing data for participants treated with Ongentys or Comtan (entacapone), a COMT inhibitor produced by Orion and marketed by Novartis in the U.S.

Both treatments reduced the average overnight “off” time, by 64% for Ongentys and by 46% for Comtan. Time to first “on” period fell by 21% with Ongentys and by 12% with Comtan.

“Reductions in overnight OFF and time to morning ON from baseline to Week 14/15 were larger with once-daily opicapone 50 mg compared to placebo or entacapone,” the researchers concluded.

In another presentation, “Long-Term Efficacy of Opicapone in the Reduction of ON-Time with Troublesome Dyskinesia in Parkinson’s Disease Patients with Motor Fluctuations and Reporting Troublesome Dyskinesia” (page S187), researchers used data from 216 patients treated with Ongentys in BIPARK-1 and BIPARK-2 to more closely evaluate the medication’s effects during “on” periods.

Specifically, participants’ diaries were used to divide “on” periods into “good on” time — periods without any troublesome symptoms, including dyskinesia (involuntary movements) — and “bad on” time, or periods when disease symptoms are largely controlled but dyskinesia is troublesome. Dyskinesia can be a side-effect of levodopa treatment, which may be exacerbated by some COMT inhibitors.

After a year of treatment, average daily “good on” time had increased by nearly two hours relative to measures taken at the trial’s start (baseline measures) — from 532.8 to 652.2 minutes per day. Average daily “bad on” time decreased by about one hour, from 119.6 to 64.5 minutes each day.

Over the year, patients’ average daily levodopa dose also lowered from 740 mg to 640 mg.

“In PD patients with motor fluctuations and reporting troublesome dyskinesia, treatment with [Ongentys] did not exacerbate troublesome dyskinesia … long-term [Ongentys] exposure, associated with a reduction in levodopa dose, led to a relevant reduction of ON-time with troublesome dyskinesia and an increase by approximately 2 h of ‘Good ON-time,’” the researchers wrote.

“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, chief medical officer at Neurocrine Biosciences, said in a press release.

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