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Efficacy

THE POWER OF TWO PHASE 3 STUDIES

ONGENTYS WAS STUDIED VS PLACEBO AND ENTACAPONE IN PHASE 3 CLINICAL TRIALS1,2

THE DOUBLE-BLIND PERIODS LASTED 14/15 WEEKS, AFTER WHICH PATIENTS HAD THE OPTION TO ENROLL IN A 1-YEAR OPEN-LABEL EXTENSION*†

Efficacy Graph 1
  • The efficacy of ONGENTYS as an adjunctive treatment to CD/LD was evaluated in two 14- to 15-week, double-blind, randomized, parallel-group studies of patients with PD experiencing “Off” episodes
  • Study 1 compared ONGENTYS to both placebo and entacapone, and Study 2 compared ONGENTYS to placebo

The primary endpoint of both studies was the mean change from baseline in “Off” time, based on 24-hour patient diaries completed 3 days prior to each of the scheduled visits. A secondary endpoint was the mean change from baseline in “Good On” time (defined as “On” time without troublesome dyskinesia), as recorded in patients’ Hauser diaries.1,2

In Study 1: 82% of patients in both groups were taking concomitant PD medications in addition to CD/LD, including dopamine agonists (68%), amantadine (23%), MAO-B inhibitors (20%), and anticholinergics (5%). In Study 2: 85% of patients in the ONGENTYS group and 81% of patients in the placebo group were taking concomitant PD medications in addition to CD/LD, including dopamine agonists (70%), amantadine (21%), MAO-B inhibitors (20%), and anticholinergics (12%).1

Reducing “Off” Time

ONGENTYS DELIVERED DAILY REDUCTIONS IN “OFF” TIME WHEN COMPARED TO PLACEBO1,2

IN TWO PHASE 3 TRIALS, ONCE-DAILY ONGENTYS REDUCED “OFF“ TIME from baseline BY 2 HOURS*

Efficacy Graph 2

ONGENTYS started to reduce “Off“ time after 1 week of treatment in 2 clinical studies (P<0.05),# and reduced “Off“ time vs placebo by 52% and 46% from baseline to Weeks 14/15 in Studies 1 and 2, respectively1,2**

Compared to ~1 hour with placebo at Weeks 14/15.2

Primary efficacy analysis.1

Adjusted P-value was calculated using a gatekeeping procedure to control for multiplicity.1

Noninferiority of ONGENTYS vs entacapone was tested only after establishing superiority of ONGENTYS to placebo. This stepwise approach ensures that ONGENTYS is noninferior to entacapone only for doses that were significantly better than placebo.2

Tests for noninferiority of ONGENTYS vs entacapone are using a noninferiority margin of 0.5 hours, and P-values are one-sided.2

Adjusted P-value was calculated using Dunnett’s alpha level adjustment to control for multiplicity.1

All ONGENTYS values were statistically significant compared to placebo (P<0.05) unless otherwise indicated. The P-values for the difference between ONGENTYS 50 mg and placebo in Study 1 were P=0.002 at Week 1, P<0.001 at Weeks 2/3, P<0.001 at Weeks 6/7, P=0.096 at Weeks 10/11 (not statistically significant), and P=0.003 at Weeks 14/15. In Study 2, the
P-values were P=0.001 at Week 1, P=0.003 at Weeks 2/3, P=0.001 at Weeks 6/7, P=0.006 at Weeks 10/11, and P=0.003 at Weeks 14/15.2

Study 1: -1.24 hours for ONGENTYS vs -0.42 hours for placebo; Study 2: -1.22 hours for ONGENTYS vs -0.47 for placebo.2

SUSTAINING “GOOD ON” TIME

“GOOD ON” TIME OVER THE COURSE OF A YEAR1

“GOOD ON“ TIME WAS MAINTAINED IN THE 1-YEAR OPEN-LABEL EXTENSION OF THE DOUBLE-BLIND STUDIES1,2*

Efficacy Graph 3
  • In a post hoc, exploratory analysis, patients who remained on ONGENTYS through the 1-year open-label period maintained increases in “Good On” time in both studies2
  • Patients who continued on ONGENTYS from the double-blind period into the open-label extension in Study 1 (n=98) and Study 2 (n=118) experienced a numerical increase of 0.6 hours and 0.5 hours LS mean “Good On” time, respectively, from the beginning of the open-label extension to the end of the study at 52 weeks2

The majority of patients—91% in Study 1 and 98% in Study 2—enrolled in the 1-year open-label extension, with completion rates of 87% and 78%, respectively2

After the double-blind period, patients were able to enroll in a 1-year OLE of ONGENTYS. Only data for patients who received ONGENTYS 50 mg in the double-blind period and enrolled into the OLE are shown for the OLE period. All patients entering the open-label period received a once-daily dose of ONGENTYS 25 mg and up-titrated to 50 mg if wearing “Off” was not sufficiently controlled. If unacceptable dopaminergic AEs appeared, the dose of CD/LD could be adjusted first, and if not sufficient, only then could the dose of ONGENTYS be down-titrated. Investigators were able to adjust the dose of ONGENTYS (5 mg, 25 mg, and 50 mg for Study 1; 25 mg and 50 mg for Study 2) based on clinical response. In Study 1, ~91% of patients who completed the double-blind period (N=542) chose to enroll, and in Study 2, ~98% of patients who completed the double-blind period (N=376) chose to enroll, with ~87% and ~78% continuing treatment through 1 year, respectively. For the majority of the extension period, investigators were able to adjust patients’ dose of CD/LD according to clinical response. Outcomes were analyzed descriptively.2,3

Secondary efficacy analysis.1

Unadjusted P-value.1

OLE data from these studies were derived from exploratory, post hoc analyses and were not powered to demonstrate statistical significance. Conclusions regarding the treatment effect of ONGENTYS cannot be drawn on the basis of OLE data. Patients who were lost to follow-up or were unable to tolerate ONGENTYS discontinued treatment, which may have raised the proportion of responders in the overall population.2

Not statistically significant.1

POST HOC ANALYSIS OF PRIMARY ENDPOINT: EARLY AND LATE SUBGROUPS

ONGENTYS reduced “Off” time in EARLY AND LATE subgroups vs placebo4*

A POST HOC ANALYSIS OF BOTH STUDIES SHOWED THAT ONGENTYS REDUCED “OFF” TIME VS PLACEBO 
IN PATIENTS WITH†:

Efficacy Graph 4

Note: These results are from post hoc analyses, and treatment effects were not prespecified and not adequately powered to examine differences. Thus, limitations should be carefully considered when interpreting these results.

What could reduced “Off” time mean for your patients taking IR CD/LD earlier in their treatment journey?

In earlier stages of PD or LD treatment.4

In the post hoc analysis of Studies 1 and 2, patients were evaluated in earlier stages of both their disease course and LD treatment pathway. Specific results (listed n values are for the ONGENTYS arm and change from baseline vs placebo): H&Y stage: <2.5 (n=113), Δ (change from baseline, minutes)=−82.1, P<0.0001; ≥2.5 (n=149), Δ=−41.1, P=0.0214; onset of motor fluctuations, years: ≤2 (n=142), Δ=−68.5, P=0.0003; >2 (n=104), Δ=−42.7, P=0.0416; daily dose of CD/LD: <4 (n=60), Δ=−59.7, P=0.0397; ≥4 (n=202), Δ=−58.6, P=0.0001; dose of CD/LD, mg: <500 (n=65), Δ=−64.6, P=0.0146; ≥500 (n=197), Δ=−57.2, P=0.0003; use of CD/LD alone: yes (n=67), Δ=−65.6, P=0.0163; no (n=195), Δ=−57.2, P=0.0002. Consistent benefit vs placebo was also seen in patients with H&Y stage ≥2.5, motor fluctuations for ≥2 years, dose frequency of CD/LD >4 times per day, dose of CD/LD ≥500 mg per day, and for patients taking adjunctive therapies.4

IN THE PHASE 3 OPEN-LABEL PERIODS

MOST PATIENTS ON ONGENTYS STAYED ON THEIR CURRENT CD/LD DOSAGE THROUGH 1 YEAR2,5

THE MAJORITY OF PATIENTS MAINTAINED THEIR DOSAGE OF CD/LD

Efficacy Graph 5

In Phase 3 clinical trials, the majority of patients taking ONGENTYS continued on the same dose of CD/LD through 1 year2,6*

Post hoc analyses of patients who received ONGENTYS 50 mg in the double-blind period. Maintained dosing data of CD/LD from the OLE period (based on prespecified Last Observation Carried Forward analysis approach).2,6

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INTERNATIONAL PARKINSON AND MOVEMENT DISORDER SOCIETY 2025 TREATMENT GUIDELINES7

  • The Movement Disorder Society (MDS) evaluated and identified a “high” level of clinical evidence for the efficacy of ONGENTYS vs placebo in Parkinson’s disease trials
  • This led to the guidelines committee rating ONGENTYS as efficacious
  • One other COMT inhibitor, entacapone, was also assessed in these guidelines
  • Clinical design flaws in entacapone trials versus placebo led to only a “moderate” level of evidence in favor of entacapone, and a conclusion that entacapone is “likely efficacious”
LEARN MORE

CLINICAL OVERVIEW

Open-Label Study Design

Open-Label 
Extension1,2
Efficacy Graph 6

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.1,2

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

CD=carbidopa; LD=levodopa.

Inclusion & Exclusion Criteria

Inclusion criteria6,8

  • 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 criteria8

  • 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.8

AE=adverse event; CD/LD=carbidopa/levodopa; COMT=catechol-O-methyltransferase; DB=double-blind; IR=immediate-release; LS=least squares; MAO=monoamine oxidase; OLE=open-label extension; PD=Parkinson’s disease.

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; 2025.
  2. Data on file. Amneal Pharmaceuticals LLC.
  3. Ferreira JJ, Lees AJ, Poewe W, et al. Effectiveness of opicapone and switching from entacapone in fluctuating Parkinson disease. Neurology. 2018;90(21):e1849-e1857.
  4. 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.
  5. 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.
  6. 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.
  7. de Bie RMA, Katzenschlager R, Swinnen BEKS, et al. Update on treatments for Parkinson’s disease motor fluctuations—An International Parkinson and Movement Disorder Society evidence-based medicine review. Mov Disord. 2025;40(5):776-794.

  8. 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.