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[Super: ONGENTYS^® (OPICAPONE) CAPSULES IS INDICATED AS ADJUNCTIVE TREATMENT TO LEVODOPA/CARBIDOPA IN PATIENTS WITH PARKINSON’S DISEASE (PD) EXPERIENCING “OFF” EPISODES.

ONGENTYS^® (OPICAPONE) CAPSULES IS CONTRAINDICATED IN PATIENTS WITH CONCOMINANT USE OF NON-SELECTIVE MONOAMINE OXIDASE (MAO) INHIBITORS, AND PHEOCHROMOCYTOMA, PARAGANGLIOMA, OR OTHER CATECHOLAMINE SECRETING NEOPLASMS.

PLEASE SEE IMPORTANT SAFETY INFORMATION AT THE END OF THIS VIDEO.

THIS VIDEO WAS SPONSORED AND DEVELOPED BY NEUROCRINE BIOSCIENCES.

THE SPEAKERS ARE PAID CONSULTANTS OF NEUROCRINE BIOSCIENCES.]

[Dr. Farmer sitting in a wooden chair within the same open office space with bookshelves. Director claps a clapboard.]

Dr. Farmer: Alright, let’s shoot this thing!

[Super: WHY ONGENTYS?]

Dr. Farmer: So you may have heard me say that one of our goals as physicians is to get the most out of each levodopa dose and to keep it working for long as possible.

[Super:
DR JILL FARMER DO, MPH
MOVEMENT DISORDER SPECIALIST]

Dr. Farmer: That’s where ONGENTYS comes into our treatment strategies.

[ONGENTYS logo appears]

Dr. Farmer: ONGENTYS^® (opicapone) capsules is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes.

[Super: ONGENTYS^® (OPICAPONE) CAPSULES IS CONTRAINDICATED IN PATIENTS WITH CONCOMINANT USE OF NON-SELECTIVE MONOAMINE OXIDASE (MAO) INHIBITORS, AND PHEOCHROMOCYTOMA, PARAGANGLIOMA, OR OTHER CATECHOLAMINE SECRETING NEOPLASMS.]

Dr. Hauser: What ONGENTYS does is help make more levodopa available to reach the brain.

[Super:
DR ROBERT A. HAUSER MD
MOVEMENT DISORDER SPECIALIST]

Dr. Hauser: ONGENTYS doubled the trough, raised the peak, and increased levodopa serum concentrations by up to 74%. It smoothed out peak-to-trough variations associated with off time.

[Super: IN A STUDY OF PATIENTS TAKING LEVODOPA/CARBIDOPA EVERY 4 HOURS, ONGENTYS RAISED MEAN LEVODOPA TROUGH CONCENTRATIONS BY UP TO 110%, RAISED MEAN LEVODOPA CONCENTRATIONS BY UP TO 35%, AND INCREASED TOTAL LEVODOPA EXPOSURE BY UP TO 74%.]

Dr. Farmer: When treating PD, what we want ideally is to keep the dopaminergic tone as stable as possible. So we are always working on ways to keep the peaks and troughs stable throughout the day. The reason being that high peaks are associated with dyskinesia and deep troughs are associated with off periods.

[Super: IN A STUDY OF PATIENTS TAKING LEVODOPA/CARBIDOPA EVERY 4 HOURS, ONGENTYS RAISED MEAN LEVODOPA TROUGH CONCENTRATIONS BY UP TO 110%, RAISED MEAN LEVODOPA CONCENTRATIONS BY UP TO 35%, AND INCREASED TOTAL LEVODOPA EXPOSURE BY UP TO 74%.]

Dr. Farmer: We’re so ingrained and so entrenched to talk to these patients about the wearing off phenomenon and how bad wearing off is. And that’s why I find the ONGENTYS trough data so impactful. In that study, the trough more than doubled—which means that there was more medicine available in the system.

And even at the end of a levodopa dose, patients had higher and smoother levodopa concentrations than without ONGENTYS. So mechanistically and pharmacokinetically speaking, that’s really promising.

Dr. Hauser: And the way that ONGENTYS accomplishes this is by targeting the COMT enzyme as it’s a once-daily COMT inhibitor. While carbidopa blocks the DDC enzyme, ONGENTYS blocks the COMT enzyme—which, in turn, helps increase overall levodopa exposure.

Dr Farmer: Now, something patients always ask is “How long do I need to wait? How long do I need to be on this medicine before I’ll notice a difference or change?”

Dr. Hauser: ONGENTYS has been proven to work rather quickly. In 2 clinical trials, ONGENTYS demonstrated a reduction of off time as early as 1 week, with significant reductions of 2 hours vs 1 hour with placebo seen at 14/15 weeks.

[Super: AT WEEK 14/15:
-1.95 HOURS VS -0.93 HOURS WITH PLACEBO (P=0.002) IN STUDY 1; ADJUSTED P VALUE WAS CALCULATED USING A GATEKEEPING PROCEDURE CONTROLLING FOR MULTIPLICITY.

-1.98 HOURS VS -1.07 HOURS WITH PLACEBO (P=0.008) IN STUDY 2; ADJUSTED P VALUE WAS CALCULATED USING DUNNETT’S ALPHA LEVEL ADJUSTMENT TO CONTROL FOR MULTIPLICITY.]

Dr. Farmer: In the 1-year open-label extension, daily off time was reduced by 2 hours and a little more than 2.5 hours in Study 1 and 2. Most people taking ONGENTYS had no changes to their levodopa/carbidopa dosing through 1 year, so we are generally keeping things the same for these patients.

[Super: FOR THE MAJORITY OF THE EXTENSION PERIOD, INVESTIGATORS WERE ABLE TO ADJUST PATIENTS’ LEVODOPA/DDCI ACCORDING TO CLINICAL RESPONSE.]

Dr. Hauser: At the end of the day, on top of your clinical experience and the patient’s medical history, you have to look at the clinical data and what a medication does for the patient. The pivotal clinical trials demonstrated ONGENTYS safety and efficacy in patients with PD experiencing off episodes. My clinical experience appears to mirror the clinical trial data.

Dr. Farmer: There are some safety considerations to factor in.

[Super: ONGENTYS may impact cardiovascular effects with concomitant use of drugs metabolized by COMT. It may cause: falling asleep during daily activities and somnolence; hypotension or syncope; dyskinesia; hallucinations and psychosis; impulse control or compulsive disorders; withdrawal-emergent hyperpyrexia; and confusion]

These are some things that need to be considered, in addition to clinical experience and a patient’s medical history, before prescribing ONGENTYS.

[Super: ADVISE PATIENTS TO MONITOR USE WITH OTHER CONCOMITANT MEDICATIONS THAT MAY IMPACT THESE CONDITIONS AND ADJUST IF NEEDED.]

Dr. Hauser: Taking ONGENTYS is fairly simple, because it’s once daily. Knowing that a lot of Parkinson’s patients are already taking levodopa/carbidopa 3 or 4 or 5 times a day, along with other medications for comorbidities…ONGENTYS is easy to take, one capsule, taken at bedtime without food, and no titration.

[Super: PATIENTS SHOULD NOT EAT FOOD 1 HOUR BEFORE AND AT LEAST 1 HOUR AFTER TAKING ONGENTYS.]

Dr. Farmer: No titration. So no calling them back into the office for tweaking—ONGENTYS is just one standard dose (50 mg, with a 25-mg dose for those with mild to moderate hepatic impairment).

[Super: ONGENTYS HAS NOT BEEN STUDIED IN PATIENTS WITH SEVERE HEPATIC IMPAIRMENT. AVOID USE IN THESE PATIENTS.]

Dr. Farmer: If something is easy, then it will be incorporated into a treatment strategy fairly well. So the no titration, taken once a day—all just make it an easy add. And that is helpful for docs, but it’s also practical for patients.

Dr. Hauser: Side effects and tolerability are always important considerations. ONGENTYS is generally well-tolerated and has a demonstrated safety profile. There was a less than 2% incidence of impulse control disorders, sleep disturbances, somnolence, urine discoloration, and diarrhea in the ONGENTYS clinical trials.

[Super: THE MOST COMMON ADVERSE REACTIONS (INCIDENCE AT LEAST 4% AND GREATER THAN PLACEBO) WERE DYSKINESIA, CONSTIPATION, BLOOD CREATINE KINASE INCREASED, HYPOTENSION/SYNCOPE, AND WEIGHT DECREASED.]

Dr. Farmer: With ONGENTYS, you have the potential for a meaningful impact on your patient’s Parkinson’s symptoms. It helps patients increase their levodopa levels, is effective, generally well tolerated, and is taken once a day.

Narrator:

Important Information
INDICATION & USAGE
ONGENTYS^® (opicapone) capsules is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease (PD) experiencing “off” episodes.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
ONGENTYS is contraindicated in patients with:

• Concomitant use of non-selective monoamine oxidase (MAO) inhibitors.
• Pheochromocytoma, paraganglioma, or other catecholamine secreting neoplasms.

WARNINGS & PRECAUTIONS
Cardiovascular Effects with Concomitant Use of Drugs Metabolized by Catechol-O-Methyltransferase (COMT)
Possible arrhythmias, increased heart rate, and excessive changes in blood pressure may occur with concomitant use of ONGENTYS and drugs metabolized by COMT, regardless of the route of administration (including inhalation). Monitor patients treated concomitantly with ONGENTYS and drugs metabolized by COMT.

Falling Asleep During Activities of Daily Living and Somnolence
Patients treated with dopaminergic medications and medications that increase levodopa exposure, including ONGENTYS, have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes has resulted in accidents. If a patient develops daytime sleepiness or somnolence, consider discontinuing ONGENTYS or adjusting other dopaminergic or sedating medications and advise patients to avoid driving and other potentially dangerous activities.

Hypotension/Syncope
Monitor patients for hypotension and advise patients about the risk for syncope. If these adverse reactions occur, consider discontinuing ONGENTYS or adjusting the dosage of other medications that can lower blood pressure.

Dyskinesia
ONGENTYS potentiates the effects of levodopa which may result in dyskinesia or exacerbate pre-existing dyskinesia. Reducing the patient's levodopa dosage or the dosage of another dopaminergic drug may reduce dyskinesia that occurs during treatment with ONGENTYS.

Hallucinations and Psychosis
Consider stopping ONGENTYS if hallucinations or psychotic-like behaviors occur. Patients with a major psychotic disorder should ordinarily not be treated with ONGENTYS.

Impulse Control/Compulsive Disorders
Patients may experience intense urges (eg, gambling, sexual, spending money, binge eating) and the inability to control them. It is important for prescribers to specifically ask patients or their caregivers about the development of new or increased urges. Re-evaluate the patient's current therapies for Parkinson's disease and consider stopping ONGENTYS if a patient develops such urges while taking ONGENTYS.

Withdrawal-Emergent Hyperpyrexia and Confusion
A symptom complex resembling neuroleptic malignant syndrome (elevated temperature, muscular rigidity, altered consciousness, and autonomic instability) has been reported in association with rapid dose reduction or withdrawal of drugs that increase central dopaminergic tone. There were no reports of neuroleptic malignant syndrome in ONGENTYS controlled clinical studies. When discontinuing ONGENTYS, monitor patients and consider adjustment of other dopaminergic therapies as needed.

ADVERSE REACTIONS
The most common adverse reactions (incidence at least 4% and greater than placebo) were dyskinesia, constipation, blood creatine kinase increased, hypotension/syncope, and weight decreased.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see neurocrine.com/ongentyspi for full Prescribing Information.

References: 1. ONGENTYS [package insert] San Diego, CA: Neurocrine Biosciences, Inc. 2020. 2. Thanvi BR, Lo TC. Long term motor complications of levodopa: clinical features, mechanisms, and management strategies. Postgrad Med J. 2004;80(946):452-458.