New real-world data for ONGENTYS®▼ (opicapone) released at the International Congress of Parkinson's Disease and Movement Disorders (MDS)

• Data from OPTIPARK study demonstrated consistently low incidence of treatment-related adverse events in clinical practice from the third week onwards in Parkinson’s disease (PD) patients with motor fluctuations treated with opicapone (as an adjunct therapy to levodopa)[1]
• Further evaluation of data from two large multinational trials (BIPARK-I and II) demonstrated opicapone’s potential for patients in the early stages of motor fluctuations and its capacity to reduce OFF-time when used as a first COMT add-on therapy to levodopa/DDCI[2]^,[3],[4],[5]
• Additional data from BIPARK-I and II showed that treatment with opicapone leads to a substantial reduction in morning OFF-time in PD patients with motor fluctuations compared with entacapone[6]

 

PORTO, Portugal, 11 September – Compelling new data being presented from 12-16 September at the MDS 2020 Virtual Congress, further support the efficacy and tolerability of ONGENTYS^® (opicapone) observed in pivotal Phase III studies. Opicapone is a once-daily catechol-O-methyltransferase (COMT) inhibitor, approved for the treatment of end-of-dose motor fluctuations in adult PD patients taking levodopa.

 

A new post-hoc analysis of the real-world OPTIPARK study showed that the majority of treatment-emergent adverse events (TEAEs) that were considered at least possibly related to opicapone occured within the first week of treatment, followed by consistently low incidence of TEAEs (<4%) from the third week onwards for 6 months. Within the first week of treatment, dyskinesia was the most frequently reported TEAE but had a very low impact on patient discontinuation (<0.5%). These observations are relevant for patient management concerning levodopa adjustment in clinical practice.¹

 

Additionally, evaluation of three further datasets from the BIPARK-I and II trials[7]^,[8] demonstrated the potential for opicapone as a first-line adjunctive therapy to levodopa in PD patients with motor fluctuations:

1. Opicapone demonstrated added benefit as a first adjunctive COMT inhibitor, in comparison with placebo and entacapone, in levodopa-treated PD patients recently diagnosed with motor fluctuations.²
2. Another evaluation confirmed these findings and provides evidence for prompt use in the motor fluctuations spectrum of patients’ disease course.⁴
3. Opicapone also showed increased effect in reducing OFF-time when used as a first add-on to levodopa or when used in combination with levodopa regimens containing other anti-PD medications.³

 

Finally, a review of home-diary data of 235 patients treated with 50 mg of opicapone or entacapone in the BIPARK-I⁷ trial showed that treatment with opicapone led to a greater increase in the proportion of patients who woke up in ON-status than treatment with entacapone (12.2% increase from baseline for opicapone compared with 7.5% for entacapone). Reduction in morning OFF-time was two-fold greater for opicapone versus entacapone (20%/h vs 10%/h).⁶

 

Professor Heinz Reichmann, Professor of Neurology at the University of Dresden, said “Opicapone has demonstrated its potential in a real-life setting, offering a generally well-tolerated adjunct to levodopa for Parkinson’s patients with motor fluctuations, with low incidence of treatment-related adverse events over time. Alongside the efficacy data published earlier this year, this is valuable additional information for clinicians considering opicapone use in routine clinical practice.”

 

Professor Soares da Silva, Director of Research & Development of Bial, shared his thoughts on the wealth of opicapone data being presented: “The amount of data we are presenting at MDS is indicative of our ongoing commitment to and investment in Parkinson’s Disease. Motor fluctuations can have a considerable impact on quality of life for people with Parkinson’s and our focus is on offering effective solutions with manageable tolerability. These new data demonstrate the potential for opicapone for use in a range of patients experiencing motor fluctuations, regardless of the point at which they occur.”

 

BIAL is presenting opicapone data from 16 abstracts at the MDS 2020 Virtual Congress.

 

Overview of key abstracts:

• Onset of Drug-Related Adverse Events in Parkinson’s Disease Patients with Motor Fluctuations Treated with Opicapone in Clinical Practice: OPTIPARK Post-Hoc Analysis – POSTER, Abstract #1029¹
• Efficacy and Safety/Tolerability of Opicapone in Catechol-O-Methyltransferase Inhibitor-Naïve Parkinson’s Disease Patients Recently Diagnosed with Motor Fluctuations – POSTER, Abstract #1028²
• Efficacy of Opicapone in Different Levodopa-Containing Treatment Regimens in Parkinson’s Disease Patients with Motor Fluctuations – POSTER, Abstract #973³
• Opicapone’s Added Benefit as a First-Line Adjunctive Therapy to Levodopa and when Used Promptly in the Motor Fluctuations Spectrum of Parkinson’s Disease: A Post-Hoc Analysis of BIPARK-I and II – POSTER, Abstract #994⁴
• Efficacy of opicapone compared to entacapone in catechol-O-methyltransferase inhibitor-naïve Parkinson’s disease patients recently diagnosed with motor fluctuations: a post-hoc conservative analysis – POSTER, Abstract #998⁵
• Effect of Opicapone and Entacapone on Early Morning-OFF Pattern in Parkinson’s Disease Patients with Motor Fluctuations – POSTER, Abstract #1071⁶

 

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About ONGENTYS^® (opicapone)[9]

Opicapone is a once-daily, peripherally-acting, third-generation, highly-selective COMT inhibitor.

 

Opicapone works by decreasing peripheral levodopa’s conversion rate into 3-O-methyldopa, thereby prolonging the duration of levodopa’s effect in reducing the OFF-time period of PD and extending the ON-time period.

 

In June 2016, the European Commission authorised ONGENTYS^® (opicapone) as an adjunct therapy to preparations of levodopa/DOPA decarboxylase inhibitors (DDCIs) in adult patients with PD and end-of-dose motor fluctuations who cannot be stabilised on those combinations. In Europe, opicapone is currently marketed in Germany, United Kingdom, Spain, Portugal, and Italy.

 

In April 2020, the U.S Food and Drug Administration (FDA) approved ONGENTYS^® (opicapone) as an add-on treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. BIAL entered into an exclusive licensing agreement with Neurocrine Biosciences in February 2017 for the development and commercialisation of opicapone in the U.S. and Canada. ONGENTYS^® (opicapone) will be available in the U.S. in September, 2020.

 

In November 2019, ONGENTYS^® (opicapone) was approved by the regulatory authorities of South Korea and will be commercialised by BIAL’s partner SK chemicals. ONGENTYS^® (opicapone) is marketed in Japan by BIAL’s partner Ono Pharmaceutical Co., Ltd., after approval of the Japanese authority in June 2020.

 

 

About the OPTIPARK Post-Hoc Analysis[10]

OPTIPARK was a Phase IV, open-label, single-arm prospective study conducted in the UK and Germany under clinical practice conditions.

 

This large real-life study in 495 patients treated with opicapone 50 mg mirrored a clinical setting through the inclusion of a broad population of fluctuating PD patients compared to the two-Phase III studies (BIPARK I and II).

 

Opicapone 50 mg was administered once daily for 3 months (German sites) or 6 months (UK sites) in addition to current treatment with levodopa/DDCI. Total daily levodopa/DDCI dose could be adjusted according to the individual’s condition throughout the study (except on Day 1).

 

The primary endpoint was Clinician’s Global Impression of Change (CGI-C) after 3 months. The secondary endpoints were Patient Global Impressions of Change (PGI-C), the Unified PD Rating Scale (UPDRS), Parkinson’s Disease Questionnaire 8 items (PDQ-8), and the Non-Motor Symptoms Assessment Scale (NMSS).

 

About the BIPARK-I study⁷

BIPARK-I was a Phase III, randomised, double-blind, active- and placebo-controlled, parallel group efficacy and safety study with an open-label, 1-year extension Phase in levodopa-treated patients with idiopathic PD and motor fluctuations.

 

The efficacy and safety of three different doses (5, 25 and 50 mg) of opicapone administered once daily, compared with entacapone (200 mg) or placebo administered with each dose of levodopa, were assessed. Opicapone 50 mg once-daily was superior to placebo and non-inferior to entacapone.

 

The study enrolled 600 patients from 106 study sites in Europe. Patients were 34–83 years old and had a diagnosis of idiopathic PD for at least 3 years; had a modified Hoehn & Yahr Scale stage of ≤3 in the ON state; had to receive optimum levodopa therapy (3–8 daily doses), stable for at least 4 weeks; had signs of end-of-dose deterioration (wearing-OFF) for at least 4 weeks with a mean daily OFF-time of at least 1.5 hours while awake, not including morning pre-first dose OFF-time; and had the ability to keep accurate 24-hour diaries. Patients were randomly assigned in a 1:1:1:1:1 ratio to opicapone 5 mg, 25 mg or 50 mg, entacapone and placebo.

 

The primary endpoint was the mean change from baseline in absolute OFF-time, as measured by 24-hour diaries. Secondary endpoints included proportion of responders, Investigators' and Subjects' Global Assessment of Change, UPDRS, quality of life, non-motor symptoms and sleep scales, tolerability, and safety assessments. Ninety percent (542/600) of patients completed the study.

 

About the BIPARK-II study⁸

BIPARK-II was a Phase III, randomised, double-blind, placebo-controlled study with an open-label 1-year extension phase in levodopa-treated patients with idiopathic PD and end-of-dose motor fluctuations.

 

The efficacy and safety of two different doses (25 and 50 mg) of opicapone, administered once daily compared with placebo, were assessed. Mean reduction in absolute OFF-time in both the 25 and 50 mg opicapone groups was greater than in the placebo arm.

 

286 patients completed the study from multinational study sites. Patient inclusion criteria and trial assessments (primary and secondary outcomes) were similar to BIPARK-I.

 

About Parkinson's disease

Parkinson's disease is a neurodegenerative, chronic, and progressive disease, characterised by massive depletion of striatal dopamine because of degeneration of dopaminergic neurons in the brain (substantia nigra).[11]

 

Epidemiological evidence points to a complex interaction between genetic vulnerability and environmental factors. PD is the second most common neurodegenerative disease after Alzheimer’s disease (AD), with a prevalence of approximately 0.5–1% among those 65–69 years of age, rising to 1–3% among persons 80 years of age and older. With an ageing population, both the prevalence and incidence of PD are expected to increase by more than 30% by 2030.¹¹

 

The diagnosis of PD is based on clinical observation and relies on three key elements: bradykinesia (slow movements), resting tremor, and rigidity (muscle stiffness). Of these, bradykinesia must be present, with at least either tremor or rigidity.¹¹ Other common symptoms are postural instability, reduced facial expression and blinking, and a slouching posture. The disease progressively incapacitates patients, causing hindrance in their lives and daily activities.

 

About BIAL

Founded in 1924, BIAL's mission is to research, develop and provide therapeutic solutions within the area of health. In the last decades, BIAL has focused strategically on quality, innovation and internationalisation. BIAL is strongly committed to therapeutic innovation, investing more than 20% of its annual turnover into research and development within neurosciences and the cardiovascular system. The company expects to introduce new drugs on the market in the coming years, strengthening its international presence based on proprietary drugs and achieving its goal of supplying innovative products to patients worldwide.

 

For more information on BIAL: www.bial.com

 

 

Contact:

Susana Vasconcelos

BIAL

susana.vasconcelos@bial.com

 

Chrissie Hartgill

Makara Health

Chrissie@makarahealth.com

+44 (0)7799 380 503

 

References

 

 

[1] Lees A, et al. Onset of Drug-Related Adverse Events in Parkinson’s Disease Patients with Motor Fluctuations Treated with Opicapone in Clinical Practice: OPTIPARK Post-Hoc Analysis. MDS 2020 Abstract #1029.

[2] Lees A, et al. Efficacy and safety/tolerability of opicapone in catechol-O-methyltransferase inhibitor-naïve Parkinson’s disease patients recently diagnosed with motor fluctuations. MDS 2020 Abstract #1028.

[3] Antonini A, et al. Efficacy of opicapone in different levodopa-containing treatment regimens in Parkinson’s disease patients with motor fluctuations. MDS 2020 Abstract #973.

[4] Ebersbach G, et al. Opicapone’s added benefit as a first-line adjunctive therapy to levodopa and when used promptly in the motor fluctuations spectrum of Parkinson’s disease: a post-hoc analysis of BIPARK-I and II. MDS 2020 Abstract #994.

[5] Ferreira JJ, et al. Efficacy of opicapone compared to entacapone in catechol-O-methyltransferase inhibitor-naïve Parkinson’s disease patients recently diagnosed with motor fluctuations: a post-hoc conservative analysis. MDS 2020 Abstract #998.

[6] Videnovic A, et al. Effect of opicapone and entacapone on early morning-OFF pattern in Parkinson’s disease patients with motor fluctuations. MDS 2020 Abstract #1071.

[7] Ferreira JJ, et al. Opicapone as an adjunct to levodopa in patients with Parkinson’s disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol. 2016;15(2):154–65.

[8] Lees A, et al. 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

[9] Ongentys^® EU SmPC. Last updated 22/04/2020

[10] Reichmann H, et al. Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study. Transl Neurodegener. 2020;9;1–9.

[11] Kouli A, et al. Parkinson’s Disease: Pathogenesis and Clinical Aspects. 2018 Ch 1.