Author: Rachael Hansford

New treatment for myasthenia gravis

Posted on November 10, 2023 by - Myasthenia Gravis

UCB receives CHMP positive opinion for rozanolixizumab for treatment of adults with generalized myasthenia gravis in Europe

  • The Committee for Medicinal Products for Human Use (CHMP) positive opinion1 is based on the pivotal Phase 3 MycarinG study in generalized myasthenia gravis (gMG) in adult patients,2 which demonstrated treatment with rozanolixizumab resulted in statistically significant and clinically meaningful improvements in gMG-specific outcomes compared to placebo,2 including everyday activities such as breathing, talking, swallowing, and being able to rise from a chair3
  • If approved by the European Commission, rozanolixizumab will be the first emerging therapy approved in Europe for adults with both anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody-positive gMG, the two most common subtypes of gMG 
  • The decision follows CHMP positive opinion for UCB’s zilucoplan in Europe for the treatment of adult patients with gMG earlier this year, alongside similar U.S. FDA and Japanese MHLW approvals of rozanolixizumab and zilucoplan for the treatment of gMG in adult patients4,5,6,7
  • UCB is the first and only company to offer a gMG-focused portfolio, providing patients and clinicians the option of two targeted therapies for both anti-AChR and anti-MuSK antibody-positive gMG

10th November 2023; UCB announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending granting marketing authorisation for rozanolixizumab as an add-on to standard therapy for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.1 

Rozanolixizumab 140 mg/ml solution for injection is a humanised IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG.2 If approved by the European Commission, rozanolixizumab will be the first emerging therapy approved in Europe for adults with both anti-AChR and anti-MuSK antibody-positive gMG, the two most common subtypes of gMG.

In September 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) also issued a positive opinion recommending granting marketing authorisation for UCB’s zilucoplan in the European Union (EU) as an add-on to standard therapy for the treatment of gMG in adult patients who are anti-AChR antibody-positive4. Zilucoplan is a once-daily subcutaneously (SC)-injected, self-administered peptide inhibitor of complement component 5 (C5 inhibitor).8

In progressing a portfolio of medicines for the treatment of gMG, with the aim of providing HCPs the option of addressing either complement activation or pathogenic antibodies for appropriate patients, UCB hopes to offer a comprehensive portfolio of targeted therapeutics, embodying a commitment to addressing the gMG community’s unmet needs.

There is a significant need to bring more targeted, well-tolerated, effective treatment options that address the pathophysiology of gMG disease. If approved by the European Commission, UCB will be the first and only company to offer a gMG-focused portfolio with rozanolixizumab and zilucoplan, providing patients and clinicians the option of two targeted therapies. We believe that the inclusion of both anti-muscle-specific tyrosine kinase (MuSK) antibody positive patients and anti-AChR positive patients within the CHMP marketing authorization recommendation for rozanolixizumab could support clinicians to tailor their prescribing decisions to meet individual needs of their patients. This latest European gMG regulatory milestone, alongside approvals for both zilucoplan and rozanolixizumab in the U.S. and Japan in recent months, further reinforces the commitment we have made to the gMG community to help transform their experiences, outcomes and expectations. We are truly proud and excited for the future.”

IIris Loew-Friedrich, Executive Vice-President and Chief Medical Officer at UCB

The CHMP opinion for rozanolixizumab is supported by safety and efficacy data from the pivotal Phase 3 MycarinG study (NCT03971422), published in The Lancet Neurology in May 2023.2 The primary efficacy endpoint was the comparison of the change from baseline between treatment groups (rozanolixizumab 7mg/kg, rozanolixizumab 10mg/kg) or placebo in the MG-ADL score at Day 43. MG-ADL is a measurement tool that assesses the impact of gMG on daily functions of 8 items that are typically affected in gMG. These include activities such as breathing, talking, swallowing, and being able to rise from a chair.3 Each item is assessed on a 4-point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function. A total score ranges from 0 to 24, with the higher scores indicating more impairment. Reductions in MG-ADL score from baseline to Day 43 were greater in the rozanolixizumab 7 mg/kg group (least-squares mean change –3.37 [SE 0.49]) and in the rozanolixizumab 10 mg/kg group (–3.40 [0.49]) than with placebo (–0.78 [0.49]; for 7 mg/kg, least-squares mean difference −2.59 [95% CI −4.09 to −1.25], p<0.001; for 10 mg/kg, −2.62 [−3.99 to −1.16], p<0.001).2

Secondary efficacy endpoints included change from baseline to Day 43 in the Myasthenia Gravis Composite (MG-C) and the Quantitative Myasthenia Gravis (QMC) scores. The MG-C is a 10-item instrument that measures the symptoms and signs of MG based on physician examination and patient history. Items are related to ptosis, double vision, eye closure, talking, chewing, swallowing, breathing, neck flexion, shoulder abduction, and hip flexion. Each item is scored on an ordinal scale with four possible categories and weighted. The total score ranges from 0 to 50, with higher scores indicating more severe impairments. The MG-C is composed of items originating from other scales (i.e., QMG, MMT, MG-ADL). A statistically significant difference favoring rozanolixizumab compared to placebo was observed in the MG-C score change from baseline to Day 43 [least squares mean difference] -3.90 (95% CI (−6.63 to −1.25), p<0.001 for rozanolixizumab 7mg/kg; least-squares mean difference −5.53 (95% CI −8.30 to −2.97), p<0.001 for rozanolixizumab 10mg/kg.2 

The QMG is a 13-item categorical grading system that assesses muscle weakness. Each item is assessed on a 4-point scale where a score of 0 represents no weakness and a score of 3 represents severe weakness. A total possible score ranges from 0 to 39, where higher scores indicate more severe impairment.9 A statistically significant difference favoring rozanolixizumab compared to placebo was observed in the QMG total score change from baseline to Day 43 [least squares mean difference -3.48 (95% CI (−5.61 to −1.58), p<0.001 for rozanolixizumab 7mg/kg; least-squares mean difference −4.76 (95% CI −6.82 to −2.86), p<0.001 for rozanolixizumab 10mg/kg.2 

The most common adverse reactions (reported in at least 10% of patients treated with rozanolixizumab) were headache, diarrhea and pyrexia.1 

gMG is a rare, chronic, heterogeneous, unpredictable autoimmune disease characterised by dysfunction and damage at the neuromuscular junction (NMJ).10,11,12 gMG has a global prevalence of 100–350 cases per every 1 million people.11 

“With the news of the CHMP’s positive opinion of rozanolixizumab, we are very proud and excited to potentially provide the gMG community with further treatment options and new hope. Following recent approvals in the U.S. and Japan, it is our commitment to bring widespread access of innovative treatment options to a broader patient population living with myasthenia gravis. And, with our two different medicines for gMG, each with a distinct mechanism of action, UCB offers the community a unique portfolio of treatments that embodies our commitment to addressing the gMG community’s unmet needs.” said Jean-Christophe Tellier, CEO, UCB. “We would like to take this time to extend our gratitude to the patients, care partners and investigators who participated in the MycarinG study, and to our employees and collaborators for their dedication and support to the gMG community.” 

This announcement follows approval of rozanolixizumab and zilucoplan by the Japanese Ministry of Health, Labour and Welfare (MHLW) for treatment of gMG in adult patients (only for patients who inadequately respond to steroids or other immunosuppressants), and approval of rozanolixizumab by the U.S. Food and Drug Administration (FDA) for the treatment of gMG in adult patients who are anti-AChR or anti-MuSK antibody positive.7,5 Orphan designation was granted by the European Commission in 2020 to rozanolixizumab for the treatment of myasthenia gravis and successfully maintained after having received the positive CHMP Opinion.13 

The CHMP’s positive opinion for rozanolixizumab is now being reviewed by the European Commission, which grants centralised marketing authorisations for medicinal products in the EU. Feedback from the European Commission is anticipated during Q1 2024. 

References

  1. EMA CHMP Confirmation. Data on file, UCB November 2023.
  2. Bril V. Efficacy and safety of rozanolixizumab in patients with generalised myasthenia gravis: a randomised, double-blind, placebo-controlled, adaptive Phase 3 study MycarinG study. Lancet Neurol. 2023;22(5):383-94
  3. Wolfe Gl, et al. Myasthenia gravis activities of daily living profile. Neurology. 1992;52(7):1487-9
  4. CHMP Positive Opinion: Zilbrysq https://www.ema.europa.eu/en/medicines/human/summaries-opinion/zilbrysq. Date accessed November 2023
  5. RYSTIGGO® U.S. Prescribing Information
  6. ZILBRYSQ® U.S. Prescribing Information.
  7. Data on file: Japan MHLW, 25 September 2023.
  8. Howard JF Jr, et al. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol. 2023;22(5):395-406. 
  9. Regnault A, et al. Measuring Overall Severity of Myasthenia Gravis (MG): Evidence for the Added Value of the MG Symptoms PRO. Neurol Ther. 2023; 12:1573–1590.
  10. National Institute of Neurological Disorders and Stroke. 2022. Myasthenia Gravis Fact Sheet. https://www.ninds.nih.gov/health-information/disorders/myasthenia-gravis?search-term=myasthenia%20gravis%20fact%20sheet. Date accessed November 2023
  11. Punga AR, et al. Epidemiology, diagnostics, and biomarkers of autoimmune neuromuscular junction disorders. Lancet Neurol. 2022;21(2):176-88.
  12. Howard JF. Myasthenia gravis: The role of complement at the neuromuscular junction. Ann N Y Acad Sci. 2018;1412:113-128.
  13. European Medicines Agency. 2020. EU/3/20/2272: Orphan designation for the treatment of myasthenia gravis. https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3202272. Date accessed November 2023
  14. US Food and Drug Administration. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=699319. Date accessed November 2023.
  15. Myasthenia Gravis Foundation of America. MG Quick Facts. https://myasthenia.org/MG-Education/MG-Quick-Facts. Date accessed November 2023
  16. Juel VC, Massey JM. Myasthenia gravis. Orphanet J Rare Dis. 2007;2:44.

Advanced Parkinson’s disease: NICE backs treatment

Posted on November 7, 2023 by - Parkinson’s Disease

27 October, 2023: The National Institute for Health and Care Excellence (NICE) has recommended a treatment for advanced Parkinson’s disease that could benefit approximately 900 patients in England. This was the first technology appraisal from NICE to look at a treatment for Parkinson’s disease.

Final draft guidance suggests that foslevodopa–foscarbidopa (Produodopa, AbbVie) should be an option for treating advanced levodopa-responsive Parkinson’s disease in adults whose symptoms include severe motor fluctuations and hyperkinesia or dyskinesia.

Treatment will be an option when available medicines are not working well enough, and only if patients cannot have apomorphine or deep brain stimulation, or these treatments no longer control symptoms.

The treatment is administered subcutaneously via an infusion pump.

NICE noted that there is some uncertainty in the treatment effects, which could lead to the benefits of foslevodopa–foscarbidopa being overestimated. It also considered that the cost-effectiveness estimates for foslevodopa–foscarbidopa were uncertain. 

However, NICE acknowledged the high level of the unmet need – and the many potential benefits of the treatment – and recommended it.

NICE say that patients already receiving the treatment can continue without any change to the funding arrangements in place before publication of the guidance until they and their NHS clinician considered it appropriate to stop.

Final guidance is expected on 29 November, 2023. [UPDATE: See Overview | Foslevodopa–foscarbidopa for treating advanced Parkinson’s with motor symptoms | Guidance | NICE]

Foslevodopa–foscarbidopa represents an important new treatment for people with advanced Parkinson’s, providing an easy-to-use option that can help them manage their symptoms more reliably and effectively.

Helen Knight, Director of Medicines Evaluation at NICE

AI medical devices – MHRA to launch the AI-Airlock

Posted on November 6, 2023 by - Artificial Intelligence

Regulatory sandbox for AI developers will assist in the development and deployment of software and AI medical devices, safely providing patients with earlier access to cutting edge innovations that improve care.

The Medicines and Healthcare products Regulatory Agency (MHRA) has announced it is taking forward its new ‘regulatory sandbox’, the AI-Airlock, that will provide a regulator-monitored virtual area for developers to generate robust evidence for their advanced technologies.

AI medical devices via MHRA AI-Airlock

Artificial Intelligence in healthcare represents the exciting potential to improve patient outcomes in many ways, for example through improving diagnoses and treatment selections, optimising medication dosages, and providing enhanced personalised care for patients. 

However, technologies like these can sometimes be challenging to test using traditional trial techniques and would therefore benefit from the AI-Airlock project’s collaborative approach to identifying and managing evidence requirements.

This means patients could benefit from faster access to developing technologies such as improved diagnostics or precision medicine as a result of this announcement.

This partnership between government, regulators and industry will see advanced AI technology used in NHS settings, with strict safety controls, ahead of navigating regulatory approval. Where successful, the AI-Airlock will help NHS patients to benefit earlier from emerging technologies before they are available anywhere else in the world.

This will support innovators to work within the current regulatory system, identify where their products need to build more evidence needed for a safety and efficacy assessment and help resolve these issues.

It follows a robust process, so manufacturers of software and AI medical devices understand and deliver what is required to ensure the real-world viability of these devices.  The process, following the ‘regulatory sandbox’ model is a world-leading mechanism to assist in safe development and deployment of software and AI medical devices.

This learning can then be shared, helping to provide an evidence base that promotes a wider understanding of the challenges and potential solutions that are available.

The AI-Airlock is designed to be a collaborative space, bringing together expertise from innovators, regulatory organisations including Approved Bodies, Government, the NHS and academia.

The recent announcement of government funding from the Department of Science, Innovation and Technology and the Department of Health and Social Care will enable development of the service, so that it will be ready to launch in April 2024.

Dr Paul Campbell, MHRA Head of Software and AI said, “Building on the success of the regulatory sandbox, we are excited to deliver a new, world-leading methodology to support safe early access to AI for patients and healthcare. We need to ensure that AI is safe and properly regulated, but in a way that doesn’t stifle innovation and access to the latest of medical technologies to improve patient care. The deployment of AI and machine learning enabled med-tech devices is challenging, given the level of complexity of these products. However, by moving beyond conventional product concepts and associated regulations, sandboxes like the AI-Airlock offer a unique and safe learning space for manufacturers to work with regulators and other parties to explore new, cutting-edge solutions to help resolve these challenges. The new AI-Airlock scheme run by the MHRA will give us answers about how best to provide safe and effective products, such as AI-driven medical devices, to the NHS and patients.”

The NHS is already a leader in the testing of new AI technologies, and I am proud that we are now funding and collaborating on this new initiative with the MHRA to help move the dial even further, to bring the latest state-of-the-art AI and its benefits to the NHS and patients faster.”

Dominic Cushnan, NHS England AI, Imaging & Deployment Director

Could shared medical appointments increase patient engagement?

Posted on November 2, 2023 by - Uncategorised

New research from ESMT Berlin finds that shared medical appointments increase engagement from patients as they ask more questions, make more comments, and exhibit higher levels of nonverbal engagement, providing greater value for other patients in the sessions.

One-on-one service delivery is often considered ideal, with individualised attention assumed to improve client outcomes. In shared service delivery, clients are served in batches, and it is feared that loss of privacy and personal one-on-one connection might undermine patient engagement. However, in the setting of eye care delivery this research shows that might not necessarily be the case.

Nazlı Sönmez from ESMT Berlin; Kavitha Srinivasan and Rengaraj Venkatesh from Aravind Eye Hospital in India; Ryan W. Buell from Harvard Business School; and Kamalini Ramdas from London Business School conducted research to understand the impact of shared medical appointments (SMAs) on patient engagement. In SMAs, patients meet with the physician in a group, each receiving attention in turn. The physician shares information specific to individual patient needs while also sharing information relevant to others with the same condition.

The researchers conducted a randomised controlled trial at the Aravind Eye Hospital with 1,000 patients undergoing glaucoma treatment over a three-year period. Groups of five patients were assigned to attend one-on-one appointments or SMAs, with each attending a total of four appointments scheduled four months apart. Using verbatim and behavioural transcripts from video recorded during the trial, researchers examined how SMAs impact patient engagement.

These results exhibit the potential for shared service delivery to increase client engagement and enhance service performance, particularly within healthcare. The design of SMAs enables patients to spend more time with the physician, albeit alongside other patients. Providers also spend more time with each patient, over 600% more time in this study, a driver of quality and value.

On average, per minute, a patient who experienced SMAs asked 33.3% more questions and made 8.6% more non-question comments. With multiple patients in an SMA, an increase in engagement resulted in patients hearing far more comments in the group setting.

Patients in SMAs also exhibited higher levels of nonverbal engagement on a wide array of measures including attentiveness, positivity, head wobbling (a South Indian gesture to signal agreement or understanding), eye contact, and end-of-appointment happiness.

“Our analysis sheds light on the benefits of designing service models that enable customers to be more helpful in serving one another, leading to more efficacious service encounters in healthcare and beyond,” says Nazlı Sönmez, Assistant Professor of Management Science at ESMT. “During our trial, our physician partners observed patients in SMAs who became motivated to ask particular questions by hearing the questions and comments of other patients.”

This research was published in the journal Manufacturing and Services Operations Management and can be viewed here.

Ipsen and World Stroke Organisation partnership focuses on improving post-stroke care

Posted on October 30, 2023 by - Stroke

Research highlights financial challenges and knowledge gaps faced by stroke survivors

Results of a new Ipsen survey highlight the stark reality faced by stroke survivors, revealing the personal and financial burdens that stroke can have on individuals and their families. The survey raises critical concerns, suggesting that many stroke survivors are not proactively made aware by their neurologist of the long-term complications that can occur following a stroke.

The survey of over 500 stroke survivors found that 9 in 10 (90%) people who were employed at the time of their stroke, said it has had an impact on their working life. One in four (25%) stroke survivors stated they have had to leave their jobs and 1 in 3 (34%) said they had to reduce their work hours.  Data shows that younger stroke survivors are particularly hard hit in terms of the impact on their careers and livelihoods, as for those who said that they had to reduce their working hours, close to half (45%) were aged 30 to 44. Similarly, of those who said they had to leave work altogether, more than a third (34%) were 30 to 44 and of the stroke survivors who said they had to find alternative employment, almost six out of ten (59%) were aged 30-44.

In addition, findings highlight that stroke also heavily impacts family members’ ability to work. Almost three quarters (74%) of all individuals who have experienced a stroke in the past three years report that a family member has had to either give up or reduce their working hours to provide care and assistance. In the UK specifically, one in five (21%) said a family member had to give up their job long-term (over a year) to care for them, while one in four (25%) said they had to reduce their work hours.

Announcing a global partnership between Ipsen and the World Stroke Organisation, focused on improving post-stroke care, Michelle Nelson, VP of Stroke Support Organizations of the World Stroke Organization said “Increasing global stroke rates among those under age 55, coupled with a projected 35% rise in stroke survivors in Europe by 2040, will significantly impact the global economy. Without action, stroke-related costs, including direct expenses and income losses, are estimated to rise to $2.31 trillion worldwide by 2050. It is therefore vital that we ensure that stroke survivors and their families have access to good quality post-stroke services to prevent recurrent strokes and optimize health and wellbeing post stroke.”

As clinicians we sometimes face significant obstacles to efficient care delivery due to a lack of patient awareness of critical symptoms of post-stroke complications and clear lines of communication between physicians, stroke survivors and caregivers. Timely and comprehensive care is vital for optimising long-term health outcomes post-stroke, particularly when it comes to spasticity. Ensuring stroke survivors are made aware and have access to accurate information and support post-discharge is critical to the success of rehabilitation.

Dr Ganesh Bavikatte, Consultant and Clinical Lead, UK

When respondents were asked what they hoped their post-stroke treatment and rehabilitation programme would deliver, almost half of all individuals questioned said the prevention of another stroke (49%). A similar proportion (46%) said they wanted to improve their mobility and movement, highlighting the high value that patients place on being able to move freely.

Despite being a top priority for patients, the survey uncovered a concerning gap in care: at least one in three stroke survivors reported that they were not proactively informed by their neurologists about potential post-stroke complications, including mobility issues such as muscle stiffness (spasticity) (38%) and muscle weakness (paresis) (38%). In addition, in Europe 1 in 3 (33%) stroke survivors who do not primarily see a stroke specialist regarding their post-stroke care, say their general practitioner does not refer them to see a stroke specialist when they experience new stroke related complications.

The findings highlight the need for a comprehensive approach to long-term stroke management that limit the economic impact and alleviates the multifaceted burdens faced by survivors and their families.

“Delayed and uncoordinated post-stroke care is costly for patients, society and healthcare systems. We know that many patients are not referred for rehabilitation and post-stroke care in a timely manner,” explains Dr Sandra Silvestri, Chief Medical Officer at Ipsen. “Ipsen is committed to improving stroke outcomes for patients. As part of this commitment, we are currently conducting a major scientific study in over 1000 patients in 7 countries to fully assess the incidence, timing, severity and patterns of post-stroke spasticity so that better treatment pathways can be identified globally for patients.”

Are CGRP medications effective against migraine in men?

Posted on October 20, 2023 by - Headache

Via Medscape: Most patients with migraine are women. This female predominance is reflected in the clinic and in clinical trials, where ~85% are women. A pharmacologist and a neurologist from the United States argue that the efficacy of calcitonin gene-related peptide (CGRP)-based migraine therapies has been proven in women but not in men, and that men should be informed of this.

In their article, which was published in JAMA Neurology, Frank Porreca, PhD, associate head of pharmacology at the University of Arizona in Tucson, and David W. Dodick, MD, professor emeritus of neurology at the Mayo Clinic Arizona in Phoenix, refer to medication that targets CGRP or its receptors.

Porreca and Dodick base their argument that CGRP-based therapies, especially the new active-substance class of gepants, are less effective in men than in women on preclinical data:

  • In mice, the injection of CGRP directly into the dura mater led to migraine-like headaches. Much lower doses were required for this in female animals than in males.
  • CGRP antibodies alleviate migraine-like pain in female mice considerably better than they do in male mice.

They also drew on observations from human studies:

  • One study with seven women and one man showed that in women, the CGRP level was elevated during a migraine attack and could be normalised again with sumatriptan. In the man, the levels were not elevated, nor could they be reduced through the application of the triptan.
  • Provocation studies, in which migraine headaches were triggered through an infusion of CGRP to prove its role in the formation of migraines, were conducted almost exclusively in women.
  • Pooled data on ubrogepant and rimegepant showed no therapeutic benefit in men. While ubrogepant demonstrated a therapeutic benefit, compared with placebo, in 8.3% (freedom from pain) and 12.4% (burdensome symptom after 2 hours) of women, a benefit was only observed in 0.2% or 0.7% of men, compared with placebo. Similar results were seen in studies of rimegepant.

Read more at Medscape.com

Reducing migraine in Major Depressive Disorder

Posted on October 17, 2023 by - Headache, Major Depressive Disorder

Teva Phase IV UNITE study shows AJOVY® (fremanezumab) reduced migraine attacks and depression symptoms in migraine sufferers with Major Depressive Disorder

  • Almost half of all migraine patients experience depression and anxiety[1]
  • Migraine patients treated with AJOVY® (fremanezumab) showed significant reductions in depressive symptoms and clinically meaningful improvements in disability outcomes
  • Data revealed at the World Congress of Neurology, Montreal, Canada

17th October, 2023: Teva Pharmaceutical Industries Ltd has announced that data from the UNITE study presented today at the World Congress of Neurology in Montreal, Canada, show that AJOVY® (fremanezumab) reduced migraine attacks and depression symptoms in migraine patients with major depressive disorder. AJOVY® is currently approved for the preventive treatment of migraine in adults.

Depression is one of the most prevalent psychiatric co-morbidities in migraine and patients with comorbid depression experience an increased risk of migraine ‘chronification’.1 This is characterised by an increase in the number of headache days, a greater degree of headache disability, decreased quality of life and a poorer response to migraine treatments.[2],[3],[4],[5]

UNITE[6] is a double-blind, randomised, placebo-controlled, Phase 4 study sponsored by Teva investigating the efficacy, safety, and impact of fremanezumab on patients with migraine and major depressive disorder.

Data revealed in an oral presentation by Dr Verena Ramirez Campos, Global Senior Medical Director at Teva, showed that patients in the study treated with fremanezumab experienced a significant reduction in Monthly Migraine Days (MMD) compared to patients on placebo, a reduction in MMD of –5.1 vs –2.9 for fremanezumab vs placebo (p<0.0001). Furthermore, a significantly higher number of patients (33%), receiving fremanezumab achieved ≥50% reduction in MMD compared to placebo (13%) during the 12 week double blind period (p<0.0001), with a sustained reduction over the longer-term.[7]

Patients who suffer from migraine and mental health disorders such as depression face a far greater burden than those suffering from either migraine or depression alone. The UNITE data presented at WCN provides further insights into the potential efficacy, safety, and quality of life benefits of AJOVY® for people with migraine and major depressive disorder.

Dr. Verena Ramirez Campos

Two further data sets were presented as posters on the study’s secondary endpoints that evaluated the impact of fremanezumab on depression[8] and disability. [9]

Treatment with fremanezumab resulted in significant reductions in depression symptoms as measured by two commonly used depression rating scores.  The mean change at week 12 for fremanezumab and placebo using the Hamilton Rating Scale for Depression (HAM-D 17) was -6.7 vs -5.4 respectively (p=0.0228) and using the Patient Health Questionnaire-9 (PHQ-9) score was -7.8 vs -6.3 respectively (p=0.0108).

Furthermore, fremanezumab demonstrated clinically meaningful improvements in disability outcomes in the study patients with a sustained reduction in their disability over the longer term. The mean change at week 12 for fremanezumab and placebo using the Headache Impact Test score (HIT-6) was -8.8 vs -5.2 respectively, (p≤0.0001) and using the Clinical Global Impression-Severity (CGI-S) score was -1.1 vs -0.8 respectively (p=0.0030).

These encouraging results indicate that fremanezumab has the potential to reduce the symptoms and cumulative burden of migraine and associated depression.  

Depression is commonly associated with migraine, and clinicians are increasingly aware of the impact of co-morbidities. We are moving towards more personalised treatment decisions in migraine which are tailored to the patient’s profile, and it is very important for treatments to demonstrate efficacy and safety in migraine patients with this particular co-morbidity.” 

Study lead author Richard Lipton M.D., Department of Neurology, Psychiatry and Behavioural Sciences at Albert Einstein College of Medicine, New York

AJOVY® (fremanezumab), a humanised monoclonal antibody (mAb) developed by Teva Pharmaceuticals, selectively targets the calcitonin gene-related peptide (CGRP), and is approved for the prevention of migraine in adults who have at least 4 migraine days per month.

References

[1] Minen MT, et al. Migraine and its psychiatric comorbidities. J Neurol Neurosurg Psychiatry. 2016; 87: 741–749.

[2] Lipton RB, et al. Migraine, quality of life and depression.  A population-based case-control study. Neurology.  2000; 55: 629–635.

[3] Buse DC, et al. Comorbid and co-occurring conditions in migraine and associated risk of increasing headache pain intensity and headache frequency: results of the migraine in America symptoms and treatment (MAST) study. J Headache Pain. 2020; 21:23.

[4] Heckman BD, et al. Do psychiatric comorbidities influence headache treatment outcomes? Results of a naturalistic longitudinal treatment study.  Pain. 2009; 146: 56-64.

[5] Walter S, Bigal ME. TEV-48125: a review of a monoclonal CGRP antibody in development for the preventive treatment of migraine. Curr Pain Headache Rep. 2015; 19:6.

[6] UNITE study protocol NCT04041284.

[7] Lipton RB, et al. Efficacy of fremanezumab treatment in reducing monthly migraine days in patients with migraine and major depressive disorder: Results from the UNITE study. Presented at World Congress of Neurology (WCN); 15–19 October 2023; Montreal.

[8] Lipton RB, et al. Efficacy of fremanezumab in reducing depression in patients with migraine and major depressive disorder: results of the UNITE study.  Presented at World Congress of Neurology (WCN); 15–19 October 2023; Montreal.

[9] McAllister P, et al. Impact of fremanezumab treatment on disability outcomes in patients with migraine and major depressive disorder: results of the UNITE study. Presented at World Congress of Neurology (WCN); 15–19 October 2023; Montreal.

New twice weekly Alzheimer’s disease patch

Posted on October 16, 2023 by - Alzheimer's Disease

Alzheimer’s disease treatment can help reduce symptoms and lessen the care burden for patients and their caregivers

September 2023: Zeyzelf® twice weekly rivastigmine transdermal patch is for the symptomatic treatment of mild to moderately severe Alzheimer’s dementia and it is the first ever patch to be launched in the UK that does not need daily application.

A study showed Zeyzelf® twice weekly is bioequivalent to daily rivastigmine patches,[i] but because it only has to be applied twice weekly, it can be easier to administer and help the patient and caregiver maintain adherence.[ii] Zeyzelf® twice weekly is also 52% less expensive than some rivastigmine patches.[iii]

In elderly patients, transdermal delivery of rivastigmine may have advantages over other delivery routes, such as oral medications, as it provides ease of use for the patient and carer, gives greater adherence to prescribed regimens and has less risk of toxicity and ‘dose dumping’.[iv] Transdermal delivery of rivastigmine, which works by blocking certain enzymes in the brain to help reduce symptoms, is also useful when elderly patients are unable to tolerate or unwilling to swallow tablets.[v]

In a comparative study, Zeyzelf® twice weekly demonstrated better adhesion properties than the daily rivastigmine patch – in 95% of patients there was satisfactory adhesion, compared to 67% with the comparison patch.[vi] Skin adhesion is one of the most important functional properties for a transdermal patch and is critical for the safety, efficacy and quality of the patch.[vii] Poor adhesion can lead to improper dosing, with additional patches having to be used, which takes up more carer and healthcare professional time. [vii]

There are currently 900,000 people with dementia in the UK, which is projected to rise to 1million by 2025 and nearly 1.6million in 2040.[viii] Alzheimer’s disease, which affects multiple brain functions, is the most common form of dementia and it is a progressive condition, with symptoms developing gradually over many years and eventually becoming more severe.[ix]

alzheimers disease patch packaging

The cost of dementia to the UK is currently £34.7billion annually – an average cost of £32,000 per person, two-thirds of which is paid by the patients and their families either in unpaid care of private social care.[x] Treatments such as Zeyzelf® which can be easier to administer and improve compliance can help reduce this care burden.

Zeyzelf® twice weekly is launched by Luye Pharma Ltd, which specialises in diseases of the central nervous system (CNS). The company believes Zeyzelf® twice weekly will offer a significant development in the treatment of Alzheimer’s and it has been well received by patients, clinicians and carers in Spain, where the product launched last year.

Zeyzelf® twice weekly patches are an important development in the treatment of Alzheimer’s dementia, where a small change can make a big difference. We know that transdermal delivery can be advantageous to both patients and carers and by having a patch that only has to be applied twice a week, rather than daily, will significantly reduce the carer burden and also potentially improve compliance. Healthcare professionals and carers all recognise that compliance is a major issue in the treatment of Alzheimer’s and Luye has launched Zeyzelf® twice weekly to help meet this unmet need. The product has been incredibly well received in Spain and is being widely used with patients and we hope this will be the same in the UK.

Andy Farrant, General Manager of Luye Pharma Ltd

ABOUT ZEYZELF®

Zeyzelf® twice weekly transdermal patches are for the treatment of mild to moderately severe Alzheimer’s dementia. The active substance of Zeyzelf® twice weekly is rivastigmine. Rivastigmine belongs to a class of substances called cholinesterase inhibitors. In patients with Alzheimer’s dementia, certain nerve cells die in the brain, resulting in low levels of the neurotransmitter acetylcholine (a substance that allows nerve cells to communicate with each other). Rivastigmine works by blocking the enzymes that break down acetylcholine: acetylcholinesterase and butyrylcholinesterase. By blocking these enzymes, rivastigmine allows levels of acetylcholine to be increased in the brain, helping to reduce the symptoms of Alzheimer’s.

Zeyzelf® twice weekly patches are available in 4.6mg or 9.5mg dose strengths.

Read more about Zeyzelf® twice weekly.

[i] Zeyzelf® twice weekly is bioequivalent to the originator Exelon daily transdermal patch (Schurad B et al. Current Alzheimer Research, 2022, 19, 541-553)

[ii] Zeyzelf® twice weekly transdermal patch, Summary of Product Characteristics, Luye Pharma Ltd. September 2023

[iii] Zeyzelf® twice weekly patches provides a considerable cost saving compared to the daily transdermal patch Exelon, with >50% cost savings. Source: NHSBSA Drug Tariff (England and Wales). September 2023

[iv] Dose dumping is a phenomenon of drug metabolism which can cause the premature and exaggerated release of a drug, which can greatly increase the concentration of a drug in the body and thereby cause adverse events or even drug-induced toxicity. Dose dumping is most commonly seen in drugs taken orally (by mouth) and digested in the gastrointestinal tract

[v] Vadivelu N, Hines R L. Clin Interv Aging, 2008 Sep; 3(3): 421-430

[vi] In a study comparing the twice weekly Zeyzelf® patch and Exelon daily patch, Zeyzelf® showed better adhesion properties than the Exelon patch despite the longer dosing intervals (Schurad B et al. Current Alzheimer Research, 2022, 19, 541-553). The EMA (European Medicines Agency) Guideline defines satisfactory adhesion as ≥ 90% of area that remained adhered at assessment. Assessments were taken 24h post application of the patches. Available online at: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-pharmacokinetic-clinical-evaluation-modified-release-dosage-forms_en.pdf

[vii] Wokovich A M et al. Eur J Pharm Biopharm. 2006 Aug;64(1):1-8

[viii] Alzheimer’s Society. https://www.alzheimers.org.uk/blog/how-many-people-have-dementia-uk#:~:text=Research%20conducted%20shows%20that%2C%20in,the%20current%20rate%20of%20prevalence (accessed September 2023)

[ix] NHS. https://www.nhs.uk/conditions/alzheimers-disease/ (accessed September 2023)

[x] Alzheimer’s Society. How much does dementia care cost. https://www.alzheimers.org.uk/blog/how-much-does-dementia-care-cost (accessed September 2023)

Switching to second line MS DMTs associated with decreased relapse rate

Posted on October 12, 2023 by - Multiple Sclerosis

People with multiple sclerosis (MS) who switch between more than two disease-modifying therapies (DMTs) have a higher risk of relapses compared with those who never switch, regardless of how well these patients adhere to their prescribed medications, according to real-world study in Canada.

According to the researchers, these findings are consistent with a greater number of treatment switches in individuals with a poor response to different therapies and/or higher disease activity.

However, among patients who ever switched treatments, those who changed to second-line DMTs had a 56% lower risk of relapse after the switch compared with those who remained on a first-line DMT. That result suggests that higher-efficacy therapies can more effectively control relapses in these patients.

Front. Neurol., 06 September 2023. Volume 14 – 2023 | https://doi.org/10.3389/fneur.2023.1243589

This provides a strong rationale for escalating therapy among those who have relapses requiring intervention