How does Ongentys work?
Parkinson’s disease is characterized by the death or deterioration of nerve cells in the brain. Some of these nerve cells produce a cell signaling molecule called dopamine that controls muscle movement. As these cells die, dopamine levels drop in the brain.
Levodopa is the current standard treatment for Parkinson’s patients. It is converted to dopamine in the brain to counteract the loss of dopamine-producing nerve cells. But as the disease progresses, patient response to levodopa diminishes. The dose could be increased, but high doses of levodopa often lead to such side effects as involuntary movements or dyskinesia.
To reduce the need for high doses of levodopa, doctors rely on treatments that block two major enzymes (DDC and COMT), both of which break down levodopa before it reaches the brain, making it less effective. Carbidopa inhibits the first enzyme, DDC. Ongentys is a COMT inhibitor, approved for use in combination with a DDC inhibitor.
Ongentys in clinical trials
Ongentys’ safety and efficacy were extensively studied in a number of clinical trials.
Two main studies were integral in its approvals: the Phase 3 BIPARK-1 (NCT01568073) and BIPARK-2 (NCT01227655) trials. Both were multinational and recruited patients diagnosed with Parkinson’s disease at least three years earlier, and with daytime “off-periods” of at least 1.5 hours despite a stable levodopa regimen.
The BIPARK-1 study enrolled 600 patients randomized to either one of three doses of Ongentys (5 mg, 25 mg, or 50 mg), another COMT inhibitor called Comtan (entacapone), or to a placebo. Patients received these in addition to their usual levodopa–carbidopa treatment for 14 to 15 weeks.
Trial results showed that both Ongentys at 50 mg and Comtan significantly reduced off episodes compared to placebo. The study also found that Ongentys, but not Comtan, led to positive ratings in both the patient global impression of change (PGI-C) and the clinical global impression of change (CGI-C).
The BIPARK-2 trial recruited more than 400 patients, who were randomized to either 25 mg or 50 mg of Ongentys, or a placebo, plus their stable levodopa regimen, for 14 to 15 weeks.
As in BIPARK-1, the BIPARK-2 trial’s results showed that Ongentys at a 50 mg dose of led to a statistically significant reduction in off times compared with placebo.
Both studies also had one-year, open-label extensions where all patients were treated with Ongentys. Results from this extension to BIPARK-1 showed lesser off-time and greater on-time in patients, regardless of whether they were continuing with Ongentys or switching to treatment from placebo. Patients treated with Ongentys at its highest dose(50 mg) in the main trial continued to maintain off-time reductions throughout this additional year of treatment.
Additional analysis of the two studies and their open-label extensions provided further evidence of Ongentys’ effectiveness. One analysis investigated levodopa use in patients on Ongentys at 50 mg daily or a placebo. At all levodopa dose levels, patients in this Ongentys group had a significantly shorter off periods. Even at low levodopa levels, patients on Ongentys at 50 mg each day had twice as large of a reduction in off-time than did placebo group patients.
Further analysis of BIPARK-1 data included patient diaries during treatment. Here, more patients given Ongentys at 50 mg were found to wake up in an “on-state” compared to those given Comtan. Among Ongentys-treated patients who an off-state upon awakening, levodopa controlled their symptoms more quickly than did Comtan. Researchers found similar results when they compared Ongentys to the placebo.
Another analysis looked at differences in on-times achieved in BIPARK-1 and -2 by grouping them into either “good” or “bad” on-times. In “good” on-times, patients had no dyskinesia or like symptoms; symptoms in “bad” on-times were mostly under control but dyskinesia was problematic. After a year of Ongentys’ use, daily “good” on-time rose by almost two hours on average, and “bad” on-time decreased by roughly an hour compared to measures taken prior to treatment. These patients over that year also reduced their average daily levodopa dose from 740 mg to 640 mg.
Side effects most commonly reported with Ongentys’ use include uncontrolled movements, constipation, low blood pressure, and unexpected weight loss.
Ongentys can cause a number of serious side effects, including falling asleep during normal activities that can include driving, dizziness, sudden uncontrolled movements, hallucinations, delusions, aggressive behavior, and unusual urges.
Last updated: March 3, 2021
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