Ongentys From Neurocrine Biosciences Inc

Pharmacy Times, October 2020, Volume 88, Issue 10

As PD progresses, patients using levodopa/carbidopa may experience off-time episodes between medication doses, when the medication is not working and motor symptoms, such as difficulty walking, slowed movement, and tremor, return.

The FDA has approved Ongentys (opicapone, Neurocrine Biosciences Inc) capsules as adjunctive treatment to levodopa/carbidopa in patients with Parkinson disease (PD) who are experiencing off-time episodes.1

PD is the second-most-common neurodegenerative disorder in the United States. About 1 million Americans are affected by PD, and an estimated 50,000 people are

diagnosed each year. As PD progresses, patients using levodopa/carbidopa may experience off-time episodes between medication doses, when the medication is not

working and motor symptoms, such as difficulty walking, slowed movement, and tremor, return.2

PHARMACOLOGY AND PHARMACOKINETICS

Ongentys is a reversible and selective catechol-O-methyltransferase (COMT) inhibitor. It demonstrates dose-proportional pharmacokinetics. The median time to maximum plasma concentration is 2 hours, and it displays a mean elimination half-life of 1 to 2 hours. When taken after a meal with moderate calories and fat, the mean overall plasma exposure decreases by 31%, the mean peak plasma concentration decreases by 62%, and the time to maximum plasma concentration is delayed by 4 hours.1

DOSAGE AND ADMINISTRATION

The dose of Ongentys is 50 mg orally once daily at bedtime. Patients should not eat food for 1 hour before and for at least 1 hour after taking their dose. Patients with moderate hepatic impairment should take 25 mg orally once daily at bedtime. Ongentys should not be used in patients with severe hepatic impairment.

CLINICAL TRIALS

The efficacy of Ongentys for the adjunctive treatment to levodopa/carbidopa in patients with PD who were experiencing off-time episodes was evaluated in 2 double-blind, parallel group, randomized trials. All patients were treated with levodopa/DOPA decarboxylase inhibitor, either alone or in combination with other PD medications. Each trial began with a levodopa/DDCI dose adjustment that lasted for up to 3 weeks, which was followed by a stable maintenance period of 12 weeks. Both trials included a 1-year open-label extension. Study 1 consisted of 600 participants who were randomized to receive Ongentys 5 mg, Ongentys 25 mg, Ongentys 50 mg, a placebo, or entacapone 200 mg for 14 or 15 weeks. Study 2 consisted of 427 participants who were randomized to receive Ongentys 25 mg, Ongentys 50 mg, or a placebo for 14 or 15 weeks. Both trials showed that Ongentys 50 mg significantly reduced off-time episodes from the baseline to week 14 or 15 compared with the placebo.1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

The use of Ongentys is contraindicated in patients who are taking nonselective monoamine oxidase inhibitors. Its use is also contraindicated in patients with a history of paraganglioma, pheochromocytoma, or other catecholamine-secreting neoplasm.

Arrhythmias, excessive changes in blood pressure (BP), and an increased heart rate may occur when Ongentys is used concomitantly with drugs metabolized by COMT. Patients taking dopaminergic medications and medications that increase levodopa exposure, including Ongentys, have reported falling asleep while engaged in daily activities. If hypotension or syncope occurs during treatment, the adjustment of BP-lowering medications or discontinuation of Ongentys should be considered. The use of Ongentys may cause or worsen dyskinesia, which may require a dose reduction of levodopa or another dopaminergic medication. Treatment with Ongentys may need to be discontinued if hallucinations or psychosis occur. Patients using Ongentys may develop compulsive disorders or impulse-control disorders, which may warrant discontinuation of the medication. Changes in medications that increase central dopaminergic tone, such as abrupt discontinuation or rapid dose reduction, have been associated with a condition similar to neuroleptic malignant syndrome, which is characterized by altered consciousness, autonomic instability, elevated temperature, and muscular rigidity. When treatment with Ongentys is discontinued, patients should be monitored, and other dopaminergic therapies may require dose adjustments. Based on animal data, Ongentys may cause fetal harm if used during pregnancy. Ongentys should not be used with end-stage renal disease.

The most common adverse effects are constipation, dyskinesia, hypotension, increased blood creatine kinase, syncope, and weight loss.1

Monica Holmberg, PharmD, BCPS, earned her PharmD at the University of Connecticut in Storrs and completed an ambulatory care residency at the Phoenix VA Health Care System in Arizona. Her practice has also included pediatrics and inpatient mental health. She lives in Phoenix.

REFERENCES

  • Ongentys [prescribing information]. San Diego, CA: Neurocrine Biosciences, Inc; 2020. Accessed June 5, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212489s000lbl.pdf
  • Neurocrine Biosciences announces FDA approval of once-daily Ongentys (opicapone) as an add-on treatment for patients with Parkinson’s Disease experiencing “off” episodes [news release]. San Diego, CA; Neurocrine Biosciences, Inc: April 27, 2020. Accessed June 5, 2020. https://parkinson.fit/feed-items/neurocrine-biosciences-announces-fda-approval-of-once-daily-ongentys-opicapone-as-an-add-on-treatment-for-patients-with-parkinsons-disease-experiencing-off-episodes/#:~:text=FDA%20Approves%20Neurocrine%20Biosciences'%20Parkinson's,daily%20pill%20for%20Parkinson's%20disease