Author: Rachael Hansford

UCB announces positive data in myasthenia gravis with zilucoplan phase 3 study results

Posted on February 4, 2022 by - Uncategorised

  • Positive topline results show the Phase 3 RAISE (NCT04115293) zilucoplan trial met primary and all key secondary endpoints in adults with generalised myasthenia gravis
  • The results show a favourable safety profile and good tolerability  
  • UCB plans to proceed with zilucoplan regulatory submissions later this year 
  • Results follow recent positive topline data from the Phase 3 MycarinG study investigating rozanolixizumab, a monoclonal antibody also being developed by UCB in the same indication
  • These results are the latest in a series of positive phase 3 data announcements by the company across its product pipeline

February 04, 2022 – 07:00 CET: UCB, a global biopharmaceutical company, announced positive topline results from the RAISE (NCT04115293) trial1 evaluating its investigational treatment zilucoplan, a self-administered, subcutaneous (SC) peptide inhibitor of complement component 5 (C5 inhibitor), versus placebo in adults with generalised myasthenia gravis (gMG).

The primary endpoint of the trial was met; a clinically meaningful and statistically significant improvement from baseline in Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 12 was observed for the zilucoplan treatment group vs placebo.

All key secondary endpoints were also met, including statistically significant improvements from baseline in Quantitative Myasthenia Gravis (QMG) score, Myasthenia Gravis Composite (MGC) score and MG-QoL15r score at Week 12 for the zilucoplan treatment group vs placebo. 

The results show zilucoplan was well-tolerated and no major unexpected safety findings were identified compared to earlier zilucoplan studies. The incidence of serious treatment emergent adverse events (TEAEs) in the zilucoplan and placebo treatment arms was similar.

The safety and efficacy of zilucoplan have not been established, and it is not approved for use in any indication by any regulatory authority worldwide. 

Based on these results, UCB plans to progress with regulatory filings for zilucoplan in gMG in the United States (US), European Union (EU) and Japan, beginning later this year.  

“gMG patients can experience varying and debilitating symptoms that impact their everyday lives in unique ways,” said James F. Howard, MD, Distinguished Professor of Neuromuscular Disease, Chief, Neuromuscular Disorders Section, University of North Carolina School of Medicine and lead investigator in the RAISE trial. “These exciting results give us additional reason to believe that zilucoplan can offer an important step forward in addressing the unmet needs of people living with gMG. As we strive to improve the management of this complex and unpredictable disease, any new medicines will be welcomed by physicians to help us realize our goal of offering effective and flexible treatment approaches in gMG which are tailored to the needs of individual patients.”

These findings from RAISE build on the positive results from the Phase 3 MycarinG study evaluating UCB’s investigational treatment rozanolixizumab, an SC-infused monoclonal antibody targeting the neonatal Fc receptor (FcRn) which also met its primary and secondary endpoints with statistical significance in gMG.2

UCB is currently the only company investigating two potential treatments with different mechanisms of action in gMG. Detailed results from both Phase 3 trials will be presented at forthcoming medical meetings in 2022.

While there has been recent progress in the treatment of MG, there is still a significant unmet need for new, effective treatment options that address the unpredictable, fluctuating symptoms of MG – some of which require urgent treatment or hospitalisation – to improve patient outcomes and quality of life. New research into additional treatment options will be welcomed by the global MG community.

Raquel Pardo, Spanish Myasthenia Association (AMES), Spain

Iris Loew-Friedrich, Executive Vice-President and Chief Medical Officer added: “This is the latest in a series of positive Phase 3 data announcements across UCB’s product pipeline validating our patient value strategy and laying foundations for future sustainable growth. Today’s results represent another significant milestone in UCB’s efforts to bring transformational outcomes to those living with myasthenia gravis. Positive results for zilucoplan and rozanolixizumab – each with a different mechanism of action – bring us one step closer to achieving our ambition of delivering choice and flexibility for a broad range of patients and physicians at each step of their treatment journey, addressing significant unmet needs and offering unique patient value. We thank the MG community for their continued insights, partnership and participation in this study.”

About Generalized Myasthenia Gravis (gMG)

Myasthenia gravis is a rare disease impacting almost 200,000 patients in the U.S., EU and Japan. ,  People living with gMG can experience a variety of symptoms, including drooping eyelids, double vision and difficulty swallowing, chewing and talking, as well as severe life- threatening weakness of the muscles of respiration.5-8

gMG is a chronic and unpredictable auto-immune disease in which pathogenic autoantibodies can inhibit synaptic transmission at the neuro-muscular junction by targeting specific proteins on the post-synaptic membrane. This disrupts the ability of the nerves to stimulate the muscle and results in a weaker contraction. gMG can occur at any age and in any race, although previous studies have shown that women are more often impacted than men.9 Complement activation, a key mediator of antibody function, is recognized as an important driver of pathology in gMG. 

About the zilucoplan RAISE study10,11 

The RAISE study (Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Generalized Myasthenia Gravis (NCT04115293)) is a multi-center, Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of zilucoplan in adult patients with gMG. 

Patients were randomised in a 1:1 ratio to receive daily subcutaneous (SC) doses of zilucoplan or placebo for 12 weeks. The study was designed to determine if complete complement inhibition can bring clinical benefit to people with gMG and if complement inhibition was effective across a broad spectrum of patients with acetylcholine receptor antibody positive (AChR Ab+) MG regardless of disease duration, prior treatment or response to previous therapies. 

The primary endpoint for RAISE study is change from baseline at Week 12 in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score, an eight-item patient-reported scale developed to assess MG symptoms and their effects on daily activities. Secondary endpoints include change in the Quantitative Myasthenia Gravis (QMG) score, the Myasthenia Gravis Composite (MGC) and the Myasthenia Gravis Quality of Life 15 revised (MG-QoL15r) from baseline to Week 12; time to rescue therapy; the percentage with minimum symptom expression (MSE) (defined as MG-ADL of 0 or 1), the percentage with a ≥3-point reduction in MG-ADL and the percentage with a ≥5-point reduction in QMG, all measured at Week 12.

For more information about the trial visit https://clinicaltrials.gov/ct2/show/NCT04115293. 

About the rozanolixizumab MycarinG study12 

The MycarinG study (NCT03971422) is a completed multi-center, Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of rozanolixizumab in adult patients with gMG, with an open-label extension. 

The primary endpoint for the MycarinG study is change in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) score. Secondary endpoints include response rates, changes in the Myasthenia Gravis Composite (MGC) score, the Quantitative MG (QMG) score, patient-reported outcomes and adverse events (AEs). 

A preliminary analysis of results shows the trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful change from baseline in the MG-ADL total score at Day 43. All secondary endpoints were also met with statistical significance. Overall, rozanolixizumab was well tolerated and no new safety signals were identified.13  

For more information about the trial, visit https://clinicaltrials.gov/ct2/show/NCT03971422. 

About Zilucoplan11,14

Zilucoplan targets complement component 5 (C5), a component of the terminal complement activation pathway, and binds to C5 with high affinity and specificity. This prevents its cleavage by C5 convertases into the complement components C5a and C5b. In addition, zilucoplan is understood to bind to the domain of C5 that corresponds to C5b and thereby block binding of C5b to complement component C6. 

Inhibition of C5 cleavage prevents the downstream assembly and activity of membrane attack complex (MAC). This dual mechanism of action of zilucoplan has the potential to prevent activation of the terminal complement pathway and downstream assembly and activity of MAC that can damage and destroy the postsynaptic membrane, disrupt ionic channel conductance and impair neuromuscular transmission. 

Zilucoplan is being investigated in the RAISE study, a multi-center, Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of zilucoplan in subjects with gMG.
Further indications that are potentially addressable by zilucoplan include amyotrophic lateral sclerosis (ALS) and other tissue-based complement-mediated disorders with high unmet medical need. 

Zilucoplan was selected as one of the first drugs to be tested in a multi-center ALS platform study sponsored by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, Boston, MA. 

The safety and efficacy of zilucoplan have not been established and it is not currently approved for use in any indication by any regulatory authority worldwide.

About Rozanolixizumab
Rozanolixizumab is a subcutaneously infused humanized monoclonal antibody that specifically binds, with high affinity, to human neonatal Fc receptor (FcRn). It has been designed to block the interaction of FcRn and Immunoglobulin G (IgG), accelerating the catabolism of antibodies and reducing the concentration of pathogenic IgG autoantibodies.15,16 

Rozanolixizumab is under clinical development with the aim of improving the lives of people with pathogenic IgG-autoantibody-driven autoimmune diseases, including gMG, primary immune thrombocytopenia (ITP), myelin oligodendrocyte glycoprotein antibody-associated disease (MOG-AD) and autoimmune encephalitis (AIE) by driving removal of pathogenic IgG autoantibodies.

The safety and efficacy of rozanolixizumab have not been established and it is not approved for use in any indication by any regulatory authority worldwide.

References

  1. Data on file. UCB. February 2022.
     
  2. UCB Press Release, December 10. 2021 https://www.ucb.com/stories-media/Press-Releases/article/UCB-announces-positive-Phase-3-results-for-rozanolixizumab-in-generalized-myasthenia-gravis Accessed February 2022
  3. Chen J, et al. Incidence, mortality, and economic burden of myasthenia gravis in China: A nationwide population-based study. Lancet Reg Health West Pac.2020;5:10063.
  4. Gilhus N. Myasthenia Gravis. N Engl J Med. 2016;375:2570-2581.
  5. Lisak, RP. Best Practice Myasthenia gravis. BMJ Best Practice. 2021. Last accessed December 2021
  6. Robertson NP, et al. Myasthenia gravis: a population based epidemiological study in Cambridgeshire, England. J Neurol Neurosurg Psychiatry. 1998;65:492-496.
  7. Kupersmith MJ et al. Development of generalized disease at 2 years in patients with ocular myasthenia gravis. Arch Neurol. 2003;60(2):243-248. 
  8. Hansen JS, et al. Mortality in myasthenia gravis: A nationwide population-based follow-up study in Denmark. Muscle Nerve. 2016;53:73-77.
  9. Myasthenia Gravis Foundation of America. Clinical Overview of MG. https://myasthenia.org/Professionals/Clinical-Overview-of-MG. Accessed November 2021.
  10. Clinical Trials.gov ‘Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Generalized Myasthenia Gravis (RAISE)’: https://clinicaltrials.gov/ct2/show/NCT04115293. Accessed November 2021.
  11. Howard JF, Jr., et al. JAMA Neurol 2020;77:582–92.
  12. Clinical Trials.gov ‘A Study to Test Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis’:  https://clinicaltrials.gov/ct2/show/NCT03971422. Accessed February 2022.
  13. Data on file. UCB. December 2021
  14. Ricardo A, et al. Blood 2015;126:939.
  15. Kiessling P, et al. The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: A randomized phase 1 study. Sci Transl Med. 2017;9(414).eaan1208
  16. Smith B, et al. Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration. MAbs.2018;10:1111-30.

Positive phase III data for Neurocrine’s Ingrezza in Huntington’s disease

Posted on January 6, 2022 by - ACNR News, Industry News

Neurocrine Biosciences has recently announced that its pipeline asset, Ingrezza (valbenazine), achieved the primary endpoint of reducing the symptoms of chorea (involuntary muscle movements) associated with Huntington’s disease (HD) in the Phase III clinical trial, KINECT-HD (NCT04102579). This will propel Ingrezza into a dominant position in the HD market, due to its convenient once-daily dosing regimen and improved safety profile, according to GlobalData, a data and analytics company.


GlobalData’s report, ‘GlobalData (2021) Huntington’s Disease: Opportunity Assessment and Forecast to 2030’, reveals that given Ingrezza’s competitive advantage and the sparseness of the US HD therapeutics market, it is set to generate strong sales of $326m for HD in the US through 2030*.


Compared to available competitors within the same therapeutic class, Ingrezza requires less-frequent dosing and does not pose the risk of increasing depression and suicidality. This is a key advantage, as the development of psychiatric and cognitive symptoms is a common comorbidity in HD patients.”

Sarah Elsayed, Neurology Analyst at GlobalData


Neurocrine plans to submit a supplemental new drug application in HD chorea, meaning that the drug could be available for HD patients in the US by Q1 2023. Key opinion leaders (KOLs) previously interviewed by GlobalData highlighted that one of the most pressing unmet needs in HD is for improved symptomatic treatments that can demonstrate superior clinical efficacy and/or safety to the current standard of care.


Chorea occurs in over 80% of patients with adult-onset HD and is not effectively managed by current treatment options. Thus, KOLs believed that Ingrezza will be a welcome addition to the HD armamentarium and will fulfill a key unmet need.”

Sarah Elsayed, Neurology Analyst at GlobalData


Currently, there are only two drugs approved in the US for the treatment of chorea associated with HD: Bausch’s Xenazine (tetrabenazine) and Teva’s Austedo. Additionally, several generic versions exist for tetrabenazine in the US, offering comparable efficacy at lower costs.

Elsayed continues: “That said, tetrabenazine generics may not be preferred by many patients as they require dosing three times per day and have a boxed warning on the label regarding the increased risk of suicidality. These issues directly affect patient compliance and subsequently limit the utility of those treatments. Ingrezza is therefore more likely to compete for new patients against Teva’s Austedo, which has been widely adopted by physicians since its launch in 2017, owing to the convenience of its twice-daily dosing. However, like tetrabenazine, Austedo also has a boxed a warning regarding the risks of depression and suicidality.”


GlobalData believes that the clinical advantages Ingrezza has shown so far in trials will allow it to move to the front lines of treatment for HD chorea and gain significant market share upon launch in the US.”

Sarah Elsayed, Neurology Analyst at GlobalData

WFNR celebrates 25th anniversary

Posted on November 5, 2021 by - Industry News

WFNR image

“Congratulations to the WFNR for all that it has achieved over the last 25 years.  Today the WFNR is a true advocate for neurorehabilitation” said Professor David Good, WFNR President as the organisation celebrates its 25th anniversary.  He continued: “We’re extremely grateful to all our members who have contributed to the success of the organisation in so many ways”.

The WFNR is a vibrant and dynamic multidisciplinary organisation, advancing the development and improving neurorehabilitation services across the world.  In addition to over 5000 members and 37 Special Interest Groups, the WFNR is now affiliated to 41 National Societies in various countries.  It hosts a biennial World Congress for Neurorehabilitation that rotates around the continents with the next WCNR heading to Vienna, Austria from the 14-17 December 2022.

Reflecting on the last 25 years Professor Michael Barnes, the founder of the WFNR said: “Our original aim has been met – to create a global organisation bringing together health professionals with an interest in neurorehabilitation.  It is now a recognised and respected sub speciality of neurology.  We now serve our patients much better than we used to and I think the WFNR has played a major role in that change. Thank you everyone!”

“Neurorehabilitation has an exciting future.  The WFNR will continue to play a major role as a ‘translational hub’, educating members about new science and technology.  There are so many new advances on the horizon; the use of brain computer interfaces, virtual and augmented reality, artificial intelligence, and better biomarkers to name just a few. The future looks bright for our patients.”  

Professor Volker Hoemberg, President-Elect

In celebration the WFNR has just launched its new website www.wfnr.co.uk and new members are always welcome.   

PhD Opportunity: Computer games to support arm rehabilitation after stroke 

Posted on February 4, 2021 by - Stroke

Background

Stroke is one of the most common causes of disability across the world. Up to 80% of acute stroke patients experience loss of arm function, which affects quality of life. Arm impairment often persists after rehabilitation has ceased. Recovery may be optimised by intensive functional training, but this can be difficult after stroke e.g. due to fatigue, pain, or depression.  Commercial games may improve arm function after stroke (Thomson et al, 2014), by increasing engagement with activities at home, providing a low-cost adjunct to rehabilitation with off the shelf technology. However, most commercial games have not been designed for people with disabilities and require adaptation. Additionally, music psychology research demonstrates the benefits of preferred music listening on mood and of rhythmic auditory stimulation on arm function in stroke survivors. At GCU, we have developed a bespoke prototype music game, which integrates rhythmic auditory stimulation with repetitive practice, based on individuals’ preferred music. This game, which uses off-the-shelf technology, has been specifically designed for stroke survivors with a range of impairments (Averell & Knox, 2019).

Aims & Objectives

To further develop this prototype to optimise its therapeutic potential and usability by considering design requirements from stroke survivors/carers, and health professionals such as occupational therapists/ physiotherapists. Based on the applicant objectives may comprise:

  1. To conduct a systematic review of music-based gaming for stroke arm rehabilitation.
  2. To further develop, with engineers in audio-technology, a prototype music-based game, through involvement of stroke survivors/carers, and health professionals.
  3. To conduct a feasibility study, exploring the feasibility, acceptability and preliminary effects of using the prototype.

Specifications

The successful applicant will be an Occupational Therapist or Physiotherapist holding the minimum of a first degree (2:1 or above). An interest in games for health, and previous experience of mixed methods or qualitative research is desirable.  This project is available as a 3 years full-time or 6 years part-time PhD study programme with expected start date of 1 October 2021

Deadline is Monday, February 22, 2021. Apply at: https://gcu.radiusbycampusmgmt.com/ssc/aform/EBc05sBc086G0x671m0xK.ssc

Contact Katie.thomson@gcu.ac.uk for more information

Reference:SHLS20061

Consistency in migraine days over course of Ajovy®

Posted on November 19, 2020 by - Uncategorised

Analysis of consistency in migraine days over the course of a dosing regimen for AJOVY® (fremanezumab-vfrm) Injection published in Headache – Analysis assessed migraine days at the beginning and end of quarterly and monthly dosing intervals

Results from a post hoc analysis of a long-term, open-label extension study assessing migraine days at the beginning and end of quarterly and monthly dosing intervals of AJOVY® (fremanezumab-vfrm) injection were published in the October 2020 issue of Headache: The Journal of Head and Face Pain.

“We are proud to share this analysis and demonstrate our continued commitment to advancing the understanding of treatment options for patients living with migraine,” said Denisa Hurtukova, MD, Vice President, Head of North America Medical Affairs, Teva. “This analysis helps us better understand patients’ experience with AJOVY, as well as the impact of quarterly and monthly dosing options.”

The post hoc analysis compared migraine days in the initial and final weeks of quarterly or monthly dosing regimens of AJOVY during up to 15 months of treatment. The analysis included 1,043 patients with chronic migraine (CM) (n=611) and episodic migraine (EM) (n=432) who were initially enrolled in the pivotal placebo controlled HALO CM and EM studies and then continued in the long-term, 12-month, multicenter, randomised, parallel group Phase 3 study with double blind dosing regimens. Patients received AJOVY either quarterly or monthly.

Utilising patients within each dosing group as their own control, we were able to analyse whether there was variability in migraine days over the course of a dosing regimen. For all time intervals analysed, the frequency of migraine days was the same in the beginning and end of the dosing period, said Joshua M. Cohen, MD, MPH, FAHS, Global Medical Therapeutic Area Lead for Migraine & Headache, Teva.

This is an important analysis for the migraine community since clinical symptoms often return or worsen before the next dose of many preventive migraine medications is due. Migraine can be a debilitating disease, so evaluating migraine days throughout a dosing regimen can be significant for healthcare providers when considering treatment options. Whenever the brain is exposed to a migraine attack, there is the possibility of increased sensitisation with progressive worsening of the frequency of migraine. A key clinical goal is to limit the amount of time the brain is exposed to migraine to reduce this risk and the number of migraine days impacting a patient before their next dose.

Andrew Blumenfeld, MD, Headache Center of Southern California, The Neurology Center, Carlsbad, CA.

The mean weekly number of migraine days at baseline was 4.0 for patients with CM taking quarterly or monthly AJOVY. For patients with EM, the mean weekly number of migraine days at baseline in the quarterly and monthly AJOVY groups were both 2.3 days.

Read more.

ACNR joins Crossref

Posted on October 14, 2020 by - ACNR News

We’re delighted to announce that ACNR has joined Crossref, and will be allocating DOI’s to new articles. We have also started adding DOI’s to existing articles, but as we have been publishing for almost 20 years we have quite a lot of content to work through!

If you have published an article with us in the past and would like a DOI allocated to it, please  email the Publisher Rachael Hansford, who will be happy to organise this for you.

Why have we joined Crossref?

ACNR is fully open access, peer reviewed and widely read around the world. 

Joining Crossref will allow us to connect our articles with a global network of online scholarly research, making content even more visible – and linking to other members within article references.

Publish with ACNR

There are no article processing or other charges for ACNR authors or their  institutions. If you would like more information about publishing with us, please see https://www.acnr.co.uk/author-guidelines/ or get in touch. We’d love to hear from you!

New real-world data for ONGENTYS®▼ (opicapone) released at the MDS

Posted on September 22, 2020 by - Parkinson’s Disease

New data presented 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.

  • 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 levodopDDCI2,3,4,5
  • 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 entacapone6

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 trials7,8 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 presented 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

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.

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 Analysis10

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.

For more information on BIAL: www.bial.com

Funding boost for AI-based epilepsy monitoring

Posted on September 22, 2020 by - Epilepsy

University spinout company Neuronostics has received funding to develop its BioEP platform, an AI-based system for faster, more accurate diagnosis of epilepsy and to monitor response to treatment with anti-epileptic drugs (AEDs). 

BioEP works by creating mathematical models of the brain using short segments of electroencephalogram (EEG) recordings. Computer simulations rapidly reveal the ease with which seizures can emerge and form the basis of the BioEP seizure risk score.

Neuronostics is developing BioEP in partnership with the University of Birmingham, where mathematician Professor John Terry, co-founder of the company, is Director of Centre for Systems Modelling & Quantitative Biomedicine. 

Professor Terry’s research aims to improve diagnosis and treatment for people with epilepsy.  He explains: 

We build personalised models of the brain using EEG that is routinely collected when seeking to diagnose epilepsy. From these models the risk of epilepsy can be quickly determined. In contrast, multiple EEG recordings are often required to reach a clinical diagnosis at present. This is expensive, time-consuming, and exposes people with suspected epilepsy to risk. 

The funding, from the National Institute for Health Research (NIHR), will enable the research partnership to progress a prototype clinical platform that can provide a risk score showing the individual’s susceptibility to seizures.  This measurement can be used in diagnosis, and as an objective assessment of response to treatment with AEDs, resulting in faster seizure control for people with epilepsy. 

The clinical utility of the BioEP seizure risk score has already been demonstrated in a cohort of people with idiopathic generalized epilepsy.1  Using just 20 seconds of an EEG recording that would be considered inconclusive in the current clinical pathway, BioEP achieved 72% diagnostic accuracy.  This matches the accuracy achieved in the current diagnostic pathway, which typically takes a year, and involves multiple follow-ups.2

The company is interested to hear from commercial partners in EEG hardware manufacturing, digital EEG analysis, and companion diagnostics or prognostics, and research and clinical partners with interests in epilepsy, traumatic brain injury and dementia.

The NIHR funding was delivered through the AI in Health and Care Award, part of the NHS AI Lab, which was launched by the UK Government earlier in 2020 to accelerate the adoption of Artificial Intelligence in health and care. 

References

  1. H Schmidt et al. A computational biomarker of idiopathic generalized epilepsy from resting state EEG Epilepsia 57: e200-e204 (2016).
  2. S Smith. EEG in the diagnosis, classification, and management of patients with epilepsy Journal of Neurology, Neurosurgery & Psychiatry 76: ii2-ii7 (2005).

About Neuronostics

Neuronostics was established in 2018 and is focused on developing clinical decision support tools and at home monitoring devices for people with suspected neurological conditions. Neuronostics is currently Medilink SW Start up of the Year and has been supported by grant funding in excess of £1M. Neuronostics’ first product – BioEP – is a revolutionary, patented, biomarker of the susceptibility to seizures in the human brain, informed by clinical EEG recordings.

About the University of Birmingham

The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 6,500 international students from over 150 countries.

About NIHR

The National Institute for Health Research (NIHR) is the nation’s largest funder of health and care research. The NIHR:

  • Funds, supports and delivers high quality research that benefits the NHS, public health and social care
  • Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
  • Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
  • Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
  • Partners with other public funders, charities and industry to maximise the value of research to patients and the economy

The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR supports applied health research for the direct and primary benefit of people in low- and middle-income countries, using UK aid from the UK government.