Ongentys (opicapone) for Parkinson’s disease
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What is Ongentys for Parkinson’s disease?
Ongentys (opicapone) is an oral therapy approved as an add-on to a combination of levodopa and carbidopa for reducing off episodes in people with Parkinson’s disease. Off episodes are periods when a medication wears off and disease symptoms return between doses.
The therapy was originally developed by Bial, which now markets it in Europe. In other regions, Bial has entered commercialization agreements with other companies for marketing the therapy. This include Neurocrine Biosciences in North America and Ono Pharmaceutical in Japan.
Therapy snapshot
| Brand Name: | Ongentys |
| Chemical Name: | Opicapone |
| Usage: | Add-on therapy to reduce off periods in Parkinson’s patients |
| Administration: | Oral capsules |
How does Ongentys work?
Parkinson’s is characterized by the progressive death of specialized nerve cells that produce a key brain chemical messenger called dopamine. As these brain cells die, dopamine levels drop and a wide range of motor and nonmotor symptoms emerge.
Dopamine’s precursor, levodopa, is a standard Parkinson’s treatment. Because it’s converted to dopamine in the brain, levodopa is used to counteract the loss of dopamine-producing nerve cells.
But as the disease progresses, a patient’s response to levodopa typically diminishes and symptoms may worsen between doses — periods called off episodes. The levodopa dose can be increased, but high doses often lead to side effects like involuntary movements, known as dyskinesia.
As such, the therapy is usually combined with compounds that block the activity of DOPA decarboxylase (DDC) and catechol-o-methyl transferase (COMT), two enzymes that convert levodopa into dopamine throughout the body before it reaches the brain.
Such combinations increase the levels of levodopa reaching the brain and help reduce levodopa doses and its associated side effects. Carbidopa is the DDC suppressor most commonly combined with levodopa (sold as Sinemet and Rytary).
Ongentys is a third-generation suppressor of COMT that’s both potent and long acting. It’s meant to be used in combination with levodopa and DDC inhibitors. Together, Ongentys and these therapies are expected to reduce off episodes in Parkinson’s patients.
Who can take Ongentys?
Ongentys was approved by the U.S. Food and Drug Administration in April 2020 for reducing off episodes in Parkinson’s patients treated with levodopa/carbidopa.
The therapy had been available in Europe since June 2016 for patients experiencing off episodes while on treatment with a combination of levodopa and a DDC suppressor. In Japan, Ongontys was approved for the same indication in June 2020.
Who should not take Ongentys?
Ongentys should not be taken by patients being given nonselective monoamine oxidase (MAO) inhibitors, which are used to treat depression and include phenelzine, isocarboxazid, and tranylcypromine.
The therapy also is not recommended for patients with a history of tumors that release dopamine and other neurohormones produced in response to stress. Further, the treatment should not be given to individuals with kidney failure and severe liver problems.
Ongentys also is not generally recommended for patients with psychosis, due to a risk of exacerbation of that disorder, and for people taking certain anti-psychotic medications, which may worsen Parkinson’s symptoms.
How is Ongentys administered?
Ongentys is available in oral capsules that come in the following strengths:
- 50 mg, with a dark blue cap and dark pink opaque body, printed with “OPC 50” in white ink, on both the cap and body
- 25 mg, with a light blue cap and light pink body, printed with “OPC 25” in blue ink, on both the cap and body.
The recommended dose is 50 mg once daily, taken at bedtime. Patients should not eat food within the one-hour period before and after taking the medication.
Dosage adjustment, including a starting dose of 25 mg per day, is recommended for people with moderate liver problems.
Ongentys in clinical trials
Approvals of Ongentys were mainly supported by positive data from two multinational, placebo-controlled, Phase 3 clinical trials: BIPARK-1 (NCT01568073) and BIPARK-2 (NCT01227655).
BIPARK-1 and BIPARK-2
The BIPARK-1 and BIPARK-2 studies included, in total, more than 1,000 adults diagnosed with Parkinson’s at least three years previously. All participants were experiencing daytime off periods of 1.5 hours or more despite being on a stable regimen of levodopa and a DDC inhibitor.
In both trials, treatment regimens were given for 14-15 weeks, or about 3.5 months, while patients continued their usual levodopa/DDC inhibitor treatment.
BIPARK-1 enrolled 600 patients who were randomly assigned to receive either Ongentys (5, 25, or 50 mg) once daily at bedtime, a matching placebo, or another COMT inhibitor called Comtan (entacapone), given at daytime doses of levodopa-related treatment.
Results showed both Ongentys at the now-approved 50 mg dose and Comtan significantly reduced daily off episodes and increased good on time — when symptoms are adequately controlled without troublesome dyskinesia — relative to a placebo.
However, the reduction in daily off periods was greater with Ongentys, at nearly two hours versus a little more than 1.5 hours. Also, the experimental therapy was the only treatment associated with an overall reduction in both patient- and physician-reported measures of disease severity.
An additional analysis showed the experimental therapy (at 50 mg) was also associated with a greater increase in the proportion of patients who woke up in an on state compared with those given Comtan. Ongentys-treated patients also were faster at reaching an on period upon awakening.
The BIPARK-2 trial recruited 427 patients, randomized to receive either Ongentys (25 or 50 mg) or a placebo, once daily, in the evening. As in BIPARK-1, the results of BIPARK-2 showed that the now-approved dose of Ongentys was superior to a placebo at significantly reducing daily off periods, by nearly two hours versus just longer than one hour.
Extension phases
After completing the treatment period, participants had the option to enroll in the trials’ respective open-label extension phases, in which all were treated with Ongentys for up to one year.
Results from the BIPARK-1 extension showed sustained reductions in off-time periods among patients who received 50 mg of Ongentys in the main trial, and deeper drops in those who switched from a placebo to the experimental therapy.
Another analysis looked at differences in daily on periods within the BIPARK-1 and BIPARK-2 trials. After a year of Ongentys use, daily good on periods rose by almost two hours on average, while bad on periods (with troublesome dyskinesia) dropped by about an hour. Over that year, patients also reduced their average daily levodopa dose from 740 mg to 640 mg.
Common side effects of Ongentys
Side effects most commonly reported in clinical trials with Ongentys use include:
- dyskinesia
- constipation
- elevated blood levels of the creatine kinase enzyme, suggesting muscle damage
- low blood pressure/fainting
- unexpected weight loss.
In clinical studies, dyskinesia or worsening of dyskinesia was reported in more than 20% of patients, and was the main reason for treatment discontinuation. Reducing the doses of levodopa- or dopamine-related treatments may help ease this complication.
Cardiovascular effects
Ongentys may cause irregular heartbeat, increased heart rate, and excessive changes in blood pressure when taken together with therapies that are degraded, or broken down, by the COMT enzymes. These patients should be closely monitored for cardiovascular events.
Falling asleep during daily activities
There are reports of people falling asleep during daily activities while on levodopa- and dopamine-related treatments. Before prescribing Ongentys treatment, healthcare providers should discuss any risk factors for increased sleepiness, such as sleep disorders and other co-prescribed medications, with patients.
Patients should inform their healthcare provider if they experience any of these issues, and treatment discontinuation should be considered.
Syncope, or fainting
The use of Ongentys may lead to low blood pressure and even cause syncope (loss of consciousness) — typically lightheadedness or fainting — when rising from a sitting or lying down position. It is therefore recommended that blood pressure be monitored while on the therapy.
Hallucinations, psychosis, and impulse control
The therapy may cause mental issues, such hallucinations (seeing or hearing things that are not real), delusions, agitation, aggressive behavior, and impulse control problems. Some reported issues with impulse control are urges to gamble and eat, or increased sexual urges.
Due to a risk of worsening psychosis, patients with a major psychotic disorder should not be treated with Ongentys. In addition, medications for psychosis that suppress the effects of dopamine-related treatments may exacerbate symptoms of Parkinson’s.
Ongentys discontinuation should be considered for patients experiencing any of these psychological issues.
Withdrawal-related high fever and confusion
High fever and confusion following rapid dose reduction or discontinuation of Parkinson’s therapies have been reported. In cases of Ongentys discontinuations, patients should be monitored and their standard medications should be adjusted as needed.
Use in pregnancy and lactation
Ongentys has not been well studied in women who are pregnant or breastfeeding. However, based on animal studies, the therapy may harm the developing fetus and may be present in breastmilk.
Patients who are pregnant or nursing, or planning to become pregnant or breastfeed while on the medication should discuss this topic with their healthcare providers.
Use in people with liver and kidney problems
Patients with mild liver dysfunction should take half of the recommended dose, or 25 mg. Those with severe liver dysfunction or with kidney failure should not take Ongentys.
Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Ongentys
In the U.S., Ongentys was approved in April 2020 as an add-on treatment for off periods in Parkinson’s patients on levodopa/carbidopa.
Clinical trials of Ongentys have not included pregnant or breastfeeding patients, so it is unclear whether the therapy is safe in such conditions. Animal data has suggested, however, that the therapy may cause fetal harm and cross to breastmilk. Patients should talk with their doctor about any plans for being pregnant or breastfeeding while on Ongentys.
Given reports of people falling asleep during daily activities while on levodopa- and dopamine-related treatments, Ongenty’s U.S. label recommends that patients starting the therapy do not drive, operate machinery, or do other potentially dangerous activities until they know how it affects them.
As each person can respond differently to a medication, there is no standard timeline for when Ongentys starts to work. In the trials that supported the therapy’s approval, a significant reduction in daily off periods could be observed in Ongentys-treated patients within the first 3.5 months of treatment. In addition, greater levodopa dose reductions were reported in patients in the first two to three weeks of treatment. But patients are advised to talk with their healthcare team on how the therapy can help in their particular case.
Hair loss and weight gain were not reported as side effects of Ongentys in clinical trials, and patients should talk with their healthcare team if such events occur. However, weight loss is a common side effect of the therapy.
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