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Efficacy

Reduced "Off" time

ONGENTYS DELIVERED SIGNIFICANT REDUCTIONS IN DAILY "OFF" TIME AT 14/15 WEEKS1,2

Study 1

Reduced daily "off" time2*

Line chart for study 1: At Week 1, ONGENTYS reduced daily 'off' time by 20%. By the end of the study, ONGENTYS reduced daily 'off' time by 32% vs placebo + CD/LD Line chart for study 1: At Week 1, ONGENTYS reduced daily 'off' time by 20%. By the end of the study, ONGENTYS reduced daily 'off' time by 32% vs placebo + CD/LD

Started to reduce "off" time after 1 week of treatment (-1.24 hours vs -0.42 hours with placebo) with a reduction in "off" time by 32% at Week 14/15 (-1.99 hours vs -1.08 hours with placebo)2‡

Once-daily ONGENTYS® (opicapone) capsules significantly reduced "off" time by 2 hours compared to 1 hour with placebo at Week 14/15.1§

*82% of patients in both groups were also taking concomitant PD medications in addition to CD/LD, including dopamine agonists (68%), amantadine (23%), MAO-B inhibitors (20%), and anticholinergics (5%).1

†P<0.05.2

‡-1.24 hours vs -0.42 hours for placebo.2

§P=0.002, adjusted P value was calculated using a gatekeeping procedure controlling for multiplicity.1

CD=carbidopa; LD=levodopa; LS=least squares; MAO-B=monoamine oxidase-B; PD=Parkinson's disease; SE=standard error.

Study 2

Reduced daily "off" time2*

Line chart for Study 2: At Week 1, ONGENTYS reduced daily 'off' time by 19%. By the end of the study, ONGENTYS reduced daily 'off' time by 33% vs placebo + CD/LD Line chart for Study 2: At Week 1, ONGENTYS reduced daily 'off' time by 19%. By the end of the study, ONGENTYS reduced daily 'off' time by 33% vs placebo + CD/LD

Started to reduce "off" time as early as 1 week (-1.22 hours vs -0.47 hours for placebo), with a reduction in "off" time by 33% at Week 14/15 (-2.11 hours vs -1.13 hours for placebo)2

Once-daily ONGENTYS significantly reduced "off" time by 2 hours compared to 1 hour with placebo at Week 14/151‡

*85% of patients taking ONGENTYS and 81% of patients taking placebo were also taking concomitant PD medications in addition to CD/LD, including dopamine agonists (70%), amantadine (21%), MAO-B inhibitors (20%), and anticholinergics (12%).1

†P<0.05.2

‡P=0.008, adjusted P value was calculated using Dunnett's alpha level adjustment to control for multiplicity.1

CD=carbidopa; LD=levodopa; LS=least squares; MAO-B=monoamine oxidase-B; PD=Parkinson's disease; SE=standard error.

Long-Term Studies

INCREASED "GOOD ON" TIME WITH ONGENTYS WAS SUSTAINED THROUGH 1 YEAR2

Study 1

ONGENTYS increased "good on" time through the 1-year open-label extensions of the double-blinded studies2

Bar chart for Study 1: At the end of the double-blind study at 14 or 15 weeks, patients taking ONGENTYS saw a mean increase of 1.72 hours in good on time vs baseline, compared with 0.92 hours with placebo. After 52 weeks in the open-label extension, patients' good on time increased by 1.98 hours vs baseline Bar chart for Study 1: At the end of the double-blind study at 14 or 15 weeks, patients taking ONGENTYS saw a mean increase of 1.72 hours in good on time vs baseline, compared with 0.92 hours with placebo. After 52 weeks in the open-label extension, patients' good on time increased by 1.98 hours vs baseline

In the open-label period, patients who switched from entacapone to ONGENTYS had almost 45 minutes additional increase in "good on" time2

  • ~91% of patients who completed the double-blind study (N=542) chose to enroll in the 1-year open-label extension period—with ~87% staying on through the end of 1 year2

  • A mean 2.00-hour reduction in daily "off" time from double-blind baseline was seen for ONGENTYS (N=98) at Week 522*

*Includes patients who were on ONGENTYS 50 mg in the double-blind period and continued on ONGENTYS in the open-label extension with dosing per the study design.2

CD=carbidopa; LD=levodopa.

Study 2

"GOOD ON" TIME INCREASED IN THE 1-YEAR OPEN-LABEL EXTENSIONS OF THE DOUBLE-BLIND STUDIES2

Bar chart for Study 2: Patients taking ONGENTYS had 1.96 hours more good on time vs baseline, compared with 0.81 hours with placebo. After 52 weeks, patients' good on time had increased by 2.28 hours vs baseline Bar chart for Study 2: Patients taking ONGENTYS had 1.96 hours more good on time vs baseline, compared with 0.81 hours with placebo. After 52 weeks, patients' good on time had increased by 2.28 hours vs baseline

  • ~98% of patients who completed the double-blind study (N=376) chose to enroll in the 1-year open-label extension period—with ~78% staying on through the end of 1 year2

  • A mean 2.64-hour reduction in daily "off" time from double-blind baseline was seen for ONGENTYS (N=118) at Week 522†

*Exploratory analysis. "Good on" time data from the open-label extension period are presented (based on prespecified Last Observation Carried Forward analysis approach) broken down by visit by dose.2

†Includes patients who were on ONGENTYS 50 mg in the double-blind period and continued on ONGENTYS in the open-label extension with dosing per the study design.2

CD=carbidopa; LD=levodopa.

Earlier Subgroups

ONGENTYS improved results in the earlier stages of PD and in earlier LD subgroups3

The following subgroups saw an improvement in "off" time vs placebo in post-hoc analyses3*:

Earlier PARKINSON'S Subgroups post-hoc analyses3

Bar chart: In patients with a Hoehn and Yahr score less than 2.5, those taking ONGENTYS with carbidopa/levodopa had 82.1 fewer minutes of daily 'off' time vs placebo Bar chart: In patients with a Hoehn and Yahr score less than 2.5, those taking ONGENTYS with carbidopa/levodopa had 82.1 fewer minutes of daily 'off' time vs placebo

Earlier Levodopa subgroups post-hoc analyses3

Bar chart: In patients whose onset of motor fluctuations was within the last 2 years, those taking ONGENTYS with carbidopa/levodopa had 68.5 fewer minutes of daily off time vs placebo Bar chart: In patients whose onset of motor fluctuations was within the last 2 years, those taking ONGENTYS with carbidopa/levodopa had 68.5 fewer minutes of daily off time vs placebo

*In the post-hoc analysis of two phase 3 trials, BIPARK 1 and BIPARK 2, patients were evaluated in earlier stages of both their disease course and levodopa treatment pathway.3

Since these results are from post-hoc analyses, treatment effects were not prespecified and not adequately powered to examine differences; and thus, limitations should be carefully considered in interpreting these results.3

CD=carbidopa; LD=levodopa; PD=Parkinson's disease.

Clinical & Real-world Data

WITH ONGENTYS, MOST PATIENTS MAINTAINED THEIR CD/LD DOSING IN BOTH CLINICAL TRIALS AND REAL-WORLD STUDIES4,5

In clinical trials, the majority of patients taking ONGENTYS were able to continue on the same dose of CD/LD through 1 year2

Graphic for Study 1: 74% of patients taking ONGENTYS had no change in their carbidopa/levodopa dose
Graphic for Study 2: 70% of patients taking ONGENTYS had no change in their carbidopa/levodopa dose

In a real-world study, after 3 months of treatment with ONGENTYS, 85% of patients were able to continue the same dose of levodopa (N=393).4†

*Post-hoc analyses. Maintained CD/LD dosing data from the open-label extension period (based on prespecified Last Observation Carried Forward analysis approach).2

†OPTIPARK was a prospective, open-label, single-arm, multicenter trial evaluating the effectiveness of ONGENTYS 50 mg in PD patients treated with levodopa who were experiencing motor fluctuations.4

CD=carbidopa; LD=levodopa; PD=Parkinson's disease.

Clinical Overview

DISCOVER THE POWER OF TWO PHASE 3 STUDIES

double-blind data2,3
Graphic: Study 1 was a 15-week double-blind study. Patients were randomized into 5 groups for ONGENTYS 5 milligrams, 25 milligrams, or 50 milligrams; entacapone 200 milligrams; or placebo. Study 2 was also a 15-week double-blind study. The design was the same as Study 1, but patients were randomized into 3 groups for ONGENTYS 25 milligrams, 50 milligrams, or placebo Graphic: Study 1 was a 15-week double-blind study. Patients were randomized into 5 groups for ONGENTYS 5 milligrams, 25 milligrams, or 50 milligrams; entacapone 200 milligrams; or placebo. Study 2 was also a 15-week double-blind study. The design was the same as Study 1, but patients were randomized into 3 groups for ONGENTYS 25 milligrams, 50 milligrams, or placebo

Primary Endpoint1,2

  • The primary efficacy endpoint in both studies was the change from baseline in absolute "off" time (average of the daily sum of "off" time on the 3 days prior to visit) at the end of the double-blind period
    • "Off" time was recorded using 24-hour diary cards on which patients rated their mobility

Secondary Endpoints1,2

  • "Off" time response: 1 hour or more reduction in absolute "off" time from baseline to endpoint
  • "On" time response: 1 hour or more increase in absolute "on" time from baseline to endpoint
  • Mean change in absolute "on" time

CD=carbidopa; LD=levodopa; V=visit.

Open-Label Extension Data2
Graphic: After their final visit in the double-blind studies, patients were able to enroll in an open-label extension that provided observation for 1 year. All patients received ONGENTYS 25 milligrams at the start of the open-label period Graphic: After their final visit in the double-blind studies, patients were able to enroll in an open-label extension that provided observation for 1 year. All patients received ONGENTYS 25 milligrams at the start of the open-label period

After the double-blind period, patients were able to enroll in a 1-year, open-label extension of ONGENTYS. Patients who had been on placebo or active comparator in the double-blind period received ONGENTYS in the open-label period.2

*Investigators were able to adjust ONGENTYS doses (5, 25, 50 mg for Study 1; 25, 50 mg for Study 2) based on clinical response.2

AE=adverse event; CD=carbidopa; D=day; LD=levodopa; OL=open-label; PSV=post-study visit; V=visit.

Key Inclusion & Exclusion Criteria

Inclusion criteria6,7

  • Male or female, 30–83 years of age
  • Clinical diagnosis of idiopathic PD for ≥3 years*
  • Hoehn and Yahr stage of 1–3†
  • At least 1-year history of clinical improvement with CD/LD therapy
  • Stable regimen of 3–8 daily doses of levodopa and other drugs for PD for ≥4 weeks before screening
  • Signs of end-of-dose deterioration for ≥4 weeks before screening with a mean total "off" time of ≥1.5 hours

Exclusion criteria6,7

  • Dyskinesia disability score >3 on item 33 of the Unified Parkinson's Disease Rating Scale (UPDRS)
  • Severe and/or unpredictable "off" periods
  • Previous surgery or deep brain stimulation for PD
  • History of liver disease or abnormal liver enzyme levels
  • Medical conditions that might interfere with assessments, such as dementia, psychiatric illness, or significant cardiovascular disease
  • History of neuroleptic malignant syndrome or nontraumatic rhabdomyolysis
  • Other COMT inhibitors or apomorphine within 1 month of screening
  • Select neuroleptics, antidepressants, MAO inhibitors, and antiemetics with antidopaminergic action withdrawn ≥1 month before screening

*United Kingdom Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria.2

†"On" state or mild unilateral disease to mild-to-moderate bilateral disease.7

CD=carbidopa; COMT=catechol-O-methyltransferase; LD=levodopa; MAO=monoamine oxidase; PD=Parkinson's disease.

Demographics

study participant demographics1,2,6

STUDY 1STUDY 2
PD Characteristics, Mean (SD)Placebo
N=120		ONGENTYS
CAPSULES 50 mg
N=115		Placebo
N=135		ONGENTYS
CAPSULES 50 mg
N=147
Age, mean (SD) years64.5 (9.2)63.5 (9.2)61.5 (8.9)65.5 (8.4)
Time since PD diagnosis, years7.7 (4.2)7.0 (3.8)7.7 (3.7)8.2 (4.5)
Time since start of levodopa treatment, years5.8 (3.7)5.3 (3.8)6.8 (3.6)7.1 (4.7)
Time since onset of end-of-dose motor fluctuations, years2.2 (1.9)2.2 (2.3)3.0 (2.3)3.2 (3.3)
Absolute time in the off state, hours6.2 (1.8)6.2 (1.8)6.1 (2.3)6.3 (2.2)
Presence of dyskinesia, (%)50 (41.7%)51 (44.3%)72 (53.3%)80 (54.4%)
Current Medications, n (%)Placebo
N=121		ONGENTYS
CAPSULES 50 mg
N=115		Placebo
N=135		ONGENTYS
CAPSULES 50 mg
N=147
Daily levodopa dose, mg/day675 (302.1)695 (337.5)714 (337.5)700 (311.9)
Number of levodopa intakes, n (SD)4.4 (1.1)4.4 (1.1)4.9 (1.4)4.9 (1.7)
Dopamine agonist (%)88 (73.3%)79 (68.7%)98 (72.6%)102 (69.4%)
MAO-B inhibitor (%)23 (19.2%)25 (21.7%)26 (19.3%)32 (21.8%)
Anticholinergics (%)7 (5.8%)8 (7.0%)13 (9.6%)14 (9.5%)
Amantadine (%)28 (23.3%)26 (22.6%)29 (21.5%)28 (19.0%)
Table: Study 1 and Study 2 participant demographics
  • In both Phase 3 studies, PD characteristics at baseline were similar across treatment groups and were representative of the target PD patient population2
    • Baseline characteristics included mean time since PD diagnosis, time since onset of levodopa treatment, time since onset of end-of-dose motor fluctuations, “off” time, and the presence of dyskinesia2
  • Baseline PD medications other than levodopa were generally similar in both studies and across treatment groups2
    • In both Phase 3 studies, the majority of patients were taking dopamine agonists, and about 20% of patients were taking MAO-B inhibitors2

MAO-B=monoamine oxidase-B; PD=Parkinson's disease; SD=standard deviation.

GENERALLY WELL TOLERATED IN CLINICAL STUDIES1

VIEW SAFETY DATA

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 have reported falling asleep while engaged in activities of daily living, including driving, which may result in accidents. Consider discontinuing ONGENTYS or adjusting other dopaminergic/sedating medications. 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 necessary, consider discontinuing ONGENTYS or adjusting the dosage of other medications that can lower blood pressure.

Dyskinesia - ONGENTYS may cause or exacerbate dyskinesia. Consider levodopa or dopaminergic medication dose reduction.

Hallucinations and Psychosis - Consider stopping ONGENTYS if these 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 ask about the development of new or increased urges. Monitor for occurrence of intense urges and consider discontinuing ONGENTYS if they occur.

Withdrawal-Emergent Hyperpyrexia and Confusion - A symptom complex resembling neuroleptic malignant syndrome can develop with rapid dose reduction or withdrawal of drugs that increase central dopaminergic tone. When discontinuing ONGENTYS, monitor patients and consider adjustment of 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 ONGENTYS full Prescribing Information.

References:

  1. ONGENTYS [package insert]. Bridgewater, NJ: Amneal Pharmaceuticals LLC; 2021.
  2. Data on file. Amneal Pharmaceuticals LLC.
  3. Rocha JF, Eberbach G, Lees A, et al. The added benefit of opicapone when used early in Parkinson's disease patients with levodopa-induced motor fluctuations: a post-hoc analysis of BIPARK-I and -II. Front Neurol. 2021;12:754016.
  4. Reichmann H, Lees A, Rocha JF, Magalhães D, Soares-da-Silva P; Optipark Investigators. Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: the OPTIPARK open-label study. Transl Neurodegener. 2020;9(1):9.
  5. Ferreira JJ, Lees A, Rocha JF, Poewe W, Rascol O, Soares-da-Silva P. Long-term efficacy of opicapone in fluctuating Parkinson's disease patients: a pooled analysis of data from two phase 3 clinical trials and their open-label extensions. Eur J Neurol. 2019:26(7):953-960.
  6. Ferreira JJ, Lees A, Rocha JF, et al. Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomized, double-blind, controlled trial. Lancet Neurol. Published December 22, 2015. doi:10.1016/S1474-4422(15)00336-1
  7. Lees AJ, Ferreira J, Rascol O, et al; BIPARK-2 Study Investigators. Opicapone as adjunct to levodopa therapy in patients with Parkinson disease and motor fluctuations: a randomized clinical trial. JAMA Neurol. 2017;74(2):197-206.