Author: Rachael Hansford

Keto diet improved life quality of RRMS patients in trial

Posted on May 6, 2022 by - Uncategorised

Eating a ketogenic diet — one low in carbohydrates and high in fats — led to less fatigue and depression for people with relapsing-remitting multiple sclerosis (RRMS) in a small clinical trial that was designed to assess the tolerability of the dietary intervention.

Measures of disability and quality of life also improved during the study while participants were eating a ketogenic diet. Overall, these results support future research to explore the effectiveness of the ketogenic diet in multiple sclerosis (MS), though researchers stressed there is not yet enough evidence to recommend this diet for MS patients outside of closely monitored clinical trials.

Results of the trial were presented at the 2022 annual meeting of the American Academy of Neurology. Full data are now reported in the Journal of Neurology, Neurosurgery and Psychiatry, in the “Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits.”

The Phase 2 trial (NCT03718247), which was sponsored by the University of Virginia, included 64 people with RRMS. Two of the participants were teenagers (ages 15 and 17); the rest were adults. The majority of participants were female and white. During the trial, participants were instructed to eat a ketogenic diet for six months.

Read more at MS News Today.

NfL test for multiple sclerosis

Posted on May 6, 2022 by - Uncategorised

Quanterix Granted Breakthrough Device Designation from U.S. FDA

Blood-based assay has the potential to serve the multiple sclerosis (MS) community in management of relapsing-remitting form of the disease

April 22, 2022 08:30 AM Eastern Daylight Time: Quanterix Corporation, a company digitising biomarker analysis with the goal of advancing the science of precision health, announced that its Simoa® neurofilament light chain (NfL) plasma test has been granted Breakthrough Device designation by the U.S. Food and Drug Administration (FDA) as a prognostic aid in assessing the risk of disease activity in patients diagnosed with relapsing-remitting MS (RRMS).

The FDA’s Breakthrough Device designation is granted to products that have the potential to offer more effective diagnosis or treatment of life-threatening diseases with an unmet medical need. The programme is designed to enable accelerated development, assessment and review processes, with the intention to provide patients with more timely access to breakthrough technologies or devices. However, Breakthrough Device designation does not guarantee that the FDA review and approval process will be shortened or that an application will be approved.

The Quanterix Simoa® NfL test is a digital immunoassay that quantitatively measures NfL in human serum and plasma and shows promise to be used in conjunction with clinical, imaging and laboratory findings as an aid in identifying RRMS patients who are at lower or higher risk for relapse within four years. This prognostic information could be useful in tailoring the therapeutic approach to more effectively treat the disease.

The designation comes on the heels of a large-scale, international study published in The Lancet Neurology, in which researchers from the University Hospital Basel and University of Basel leveraged Quanterix’ ultra-sensitive Simoa® technology to help establish a new method for clinicians to identify and interpret elevated values of sNfL in individual MS patients. Along with this research, the Simoa® NfL assay was referenced in at least 20 studies presented at the American Academy of Neurology (AAN) 74th Annual Meeting, further validating the biomarker’s potential utility.

“There has been an ever-growing body of research with the Simoa® NfL blood test supporting NfL as a reliable biomarker for MS disease activity prognosis and treatment response monitoring,” said Dr. Mark S. Freedman, Professor of Neurology and Director of Multiple Sclerosis Research at the Ottawa Hospital.

The FDA’s grant of Breakthrough Device designation for this test has the potential to help the multiple sclerosis community further advance the optimal use of NfL measurements in both research and clinical practice aimed at more effective therapeutic management of the disease for the millions of patients suffering from the condition.

Dr. Mark S. Freedman, Professor of Neurology and Director of Multiple Sclerosis Research at the Ottawa Hospital

This is the second test from Quanterix to receive Breakthrough Device status – the company’s phospho-Tau 181 (pTau-181) assay for Alzheimer’s disease received the designation in 2021.

To learn more about Quanterix’ Simoa® technology, visit: https://www.quanterix.com/technology.

Using telemedicine in neuro-oncology – practical guidance

Posted on May 4, 2022 by - Uncategorised

The COVID-19 pandemic has ensured the expansion of telemedicine into nearly every medical specialty. This article summarises current practice and makes recommendations for integrating virtual care in the practice of neuro-oncology. It identifies current telemedicine practice, provides practical guidance for conducting telemedicine visits, and generates recommendations for integrating virtual care into neuro-oncology practice. Practical aspects of telemedicine are summarised including when to use and not use telemedicine, how to conduct a virtual visit, who to include in the virtual encounter, unique aspects of telehealth in neuro-oncology, and emerging innovations. Read the article in Neuro-Oncology Practice.

Study links gut microbiota strains with more severe strokes and poorer post-stroke recovery

Posted on May 4, 2022 by - Uncategorised

A new study has identified strains of gut microbiota that are associated with more severe strokes and worse post-stroke recovery, revealing that the gut microbiome could be an important factor in stroke risk and outcomes1.

The study, presented 28 April 2022 at the European Stroke Organisation Conference (ESOC 2022) pinpointed specific groups of bacteria associated with poorer neurological recovery from ischaemic stroke both in the acute phase (24 hours) and after three months.

The research identified multiple types of bacteria were associated with ischemic stroke risk, including Fusobacterium and Lactobacillus. Negativibacillus and Lentisphaeria were associated with a more severe stroke in the acute phase (at 6 and 24 hours respectively) and Acidaminococcus related to poor functional outcomes at three months. 

Dr Miquel Lledós, lead author from the Sant Pau Research Institute Stroke Pharmacogenomics and Genetics Laboratory, Barcelona, Spain, commented “The influence of the gut microbiome – the trillions of bacteria and other microorganisms that live in the gut – is a modifiable risk factor associated with the risk of stroke and with post-stroke neurological outcomes. However, most research has previously been done in animal models.”

“In this study we took faecal samples – the first samples taken after the event – from 89 humans who’d suffered an ischaemic stroke. Comparing with a control group, we were able to identify multiple groups of bacteria that were associated with a higher risk of ischaemic stroke.”

An ischaemic stroke occurs when a clot or other blockage blocks the blood supply to the brain and is the most common type of stroke. In Europe, 1.3 million people suffer a stroke every year and it is the second most common single cause of death2.

“The discovery opens the exciting prospect that, in the future, we may be able to prevent strokes or improve neurological recovery by examining the gut microbiota. In other pathologies, clinical trials are being carried out where researchers replace the intestinal flora through dietary changes or faecal transplantation from healthy individuals and this should be studied further in the stroke field.”

The association between certain strains of gut bacteria and risk of ischaemic stroke was reinforced in another study presented at ESOC this week by a team from Yale University, Connecticut, USA3.

The researchers analysed statistics from the Flemish Gut Flora Project and the MEGASTROKE consortium, using a technique called Mendelian Randomisation (MR) which measures variation in genes to examine the causal effect of an outcome or exposure. The study identified 20 microbial traits significantly associated with the risk of developing at least one subtype of ischaemic stroke.

References

  1. Influence of the gut microbiome in ischemic stroke risk and ischemic stroke outcome, presented at the European Stroke Organisation Conference, 4 May 2022.
  2. Status and Perspectives of Acute Stroke Care in Europe | Stroke (ahajournals.org)
  3. The gut microbiome influences the risk of acute ischemic stroke: a mendelian randomization study, presented at the European Stroke Organisation Conference, 5 May 2022.
  4. https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.029606
  5. https://www.euro.who.int/en/health-topics/noncommunicable-diseases/cardiovascular-diseases/data-and-statistics

Pregabalin may slightly increase risk of major congenital malformations

Posted on May 3, 2022 by - Uncategorised

20 April 2022: The Medicines and Healthcare products Regulatory Agency (MHRA) has issued a drug safety update on the use of pregabalin in pregnancy, after a new study suggests that it may slightly increase the risk of major congenital malformations.

Advice for healthcare professionals is that potentially fertile women should continue to use effective contraception during treatment with pregabalin, and that use of the drug in pregnancy should be avoided unless it is “clearly necessary”.

The latest alert was prompted by the pregabalin pregnancy outcomes study, an observational cohort study in Denmark, Finland, Norway, and Sweden that included over 2700 pregnancies with pregabalin exposure during the first trimester, the largest population-based study to date. 

Read more.

EC marketing authorisation for Vydura for migraine

Posted on May 2, 2022 by - Headache

Pfizer Inc and Biohaven Pharmaceutical Holding Company Ltd announced on 27th April that the European Commission (EC) has granted marketing authorisation for VYDURA® (rimegepant), a calcitonin gene-related peptide (CGRP) receptor antagonist for both the acute treatment of migraine with or without aura, and prophylaxis of episodic migraine in adults who have at least four migraine attacks per month.

VYDURA®, an orally disintegrating tablet, is the first medicine approved for both acute and prophylactic treatment of migraine in the European Union (EU). Migraine is a leading cause of disability worldwide with approximately one in ten people living with the condition in Europe alone. Globally, migraine disproportionately affects women by three to four times compared to men.

There is a significant unmet need for people in the European Union living with the pain and disability caused by frequent migraines. The comprehensive clinical programme has established VYDURA’s efficacy and safety as both an acute and preventive treatment of migraine. Studies in acute migraine demonstrated a rapid and long-lasting relief of migraine headache and other symptoms with a single dose, while the prevention study found a significant reduction in migraine attacks with every other day dosing. We have great confidence in the positive impact VYDURA could have on people living with this debilitating condition in the EU.

Nick Lagunowich, Global President, Pfizer Internal Medicine.

Results from the Phase 3 study published in Lancet demonstrated that a single dose of rimegepant provided superior pain reduction and associated symptoms of migraine at two hours compared to placebo. The prevention study, also published in Lancet, demonstrated that rimegepant taken every other day provided superior reduction in the number of days per month with migraine in Weeks 9 –12 of the 12-week treatment period compared to placebo, that was maintained with continued dosing during the 12-month open-label extension period.

Today’s approval marks a huge step forward for patients in Europe who are living with migraine. Migraine is often overlooked and undertreated, resulting in substantial disability with suboptimal care for patients. VYDURA’s promising efficacy and favorable benefit-risk profile spark hope for people in need of new migraine treatment options. This approval has the potential to advance the standard of care for migraine in the EU and I am hopeful it will improve the quality of life for many people living with the burden of this prevalent neurological disease.

Professor Peter Goadsby, Director of the National Institute for Health and Care Research (NIHR) Clinical Research Facility and Professor of Neurology at King’s College London.

The Marketing Authorisation follows the recommendation for approval by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) in February. The EC approval will be valid for all 27 EU member states as well as Iceland, Liechtenstein, and Norway and local reimbursement approval will follow. Assessment of the marketing authorisation application by the Medicines & Healthcare products Regulatory Agency (MHRA) is underway and approval is expected to shortly follow in the UK.

About VYDURA® (rimegepant)
VYDURA® targets a key component of migraine by reversibly blocking CGRP receptors. CGRP is increased during a migraine attack, dilates blood vessels and is involved in nociceptor signaling. CGRP receptor antagonists work by reversibly blocking CGRP receptors, thereby inhibiting the biologic activity of the endogenous CGRP neuropeptide.

The Marketing Authorisation for VYDURA® was based, in part, on the review of the results from three Phase 3 studies for acute treatment, a long-term, open-label safety study in acute treatment of migraine and a Phase 3 study with a 1-year open-label extension in the preventive treatment of migraine. VYDURA® is taken orally as needed, up to once daily, to stop migraine attacks or taken every other day to help prevent migraine attacks.

The most frequent adverse event in clinical trials with VYDURA® was nausea, occurring in 3% of patients compared to 1% with placebo, while hypersensitivity reactions including rash occurred in less than 1% of patients. Less than 2% of patients discontinued from VYDURA® due to adverse events. VYDURA® does not have addiction potential and was not associated with medication overuse headache or rebound headache in clinical trials, although overuse of any type of medicinal products for headache can make them worse.

VYDURA® is commercialised as Nurtec® and Nurtec® ODT outside Europe. It is commercialised in the U.S. for the acute treatment of migraine and for the preventive treatment of episodic migraine in adults, and ex-U.S. is approved for the acute treatment of migraine in Kuwait and the United Arab Emirates, and for acute treatment of migraine and preventive treatment of episodic migraine in Israel.

Earlier this year, Pfizer and Biohaven entered into an agreement for the commercialisation of VYDURA®. Under the terms of the agreement, Pfizer has commercialisation rights to rimegepant in markets outside the U.S. Biohaven continues to lead research and development globally and retains the U.S. market.

US approval for ULTOMIRIS® for gMG

Posted on April 30, 2022 by - Uncategorised

ULTOMIRIS® (ravulizumab-cwvz) approved in the US for Adults with Generalised Myasthenia Gravis

First and only long-acting C5 complement inhibitor to demonstrate clinical improvement in patients with generalised myasthenia gravis

ULTOMIRIS showed early effect and lasting improvement in activities of daily living and has potential to reduce treatment burden with dosing every 8 weeks

April 28, 2022: ULTOMIRIS®(ravulizumab-cwvz) has been approved in the US for the treatment of adult patients with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive, which represents 80% of people living with the disease.1-5

The approval by the Food and Drug Administration (FDA) was based on positive results from the CHAMPION-MG Phase III trial, in which ULTOMIRIS was superior to placebo in the primary endpoint of change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 26, a patient-reported scale that assesses patients’ abilities to perform daily activities.1

This FDA action marks the first and only approval for a long-acting C5 complement inhibitor for the treatment of gMG.

gMG is a rare, debilitating, chronic, autoimmune neuromuscular disease that leads to a loss of muscle function and severe weakness.6 The diagnosed prevalence of gMG in the US is estimated at approximately 90,000.7

Despite recent advances, managing gMG is complex. Earlier intervention can preserve function and quality of life. This approval offers patients, including those with milder symptoms, a long-acting C5 inhibitor with early onset and reliable efficacy.

Professor James F. Howard, Jr, MD, Department of Neurology at The University of North Carolina School of Medicine and lead primary investigator in the CHAMPION-MG trial.

Samantha Masterson, Chief Executive Officer, Myasthenia Gravis Foundation of America (MGFA), said: “gMG takes a physical and emotional toll on those living with the disease. We are grateful for continued innovation and research into new treatment and dosing options to meet the needs of more patients and reduce the treatment burden. With the approval of ULTOMIRIS, we’re excited that MG patients now have another option to consider as part of their personalized treatment strategies that may offer more convenience and improve muscle weakness.”

Marc Dunoyer, Chief Executive Officer, Alexion, said: “Since bringing forward thefirst complement inhibitor, we’ve continued to listen to the community and focused innovation on the needs of gMG patients. We’re proud to deliver on this commitment with today’s approval. ULTOMIRIS, the only long-acting C5 inhibitor, will benefit a broader range of patients, including those with milder symptoms. As presented at the 2022 American Academy of Neurology Annual Meeting, ULTOMIRIS has demonstrated clinical benefit through 60 weeks, with treatment every eight weeks, compared to SOLIRIS every two weeks.”

In the trial, the safety profile of ULTOMIRISwas comparable to placebo and consistent with that observed in Phase III trials of ULTOMIRIS in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). The most common adverse reactions in patients receiving ULTOMIRIS were upper respiratory tract infection and diarrhea.1

Results from the CHAMPION-MG trial were recently published online in NEJM Evidence and presented at the 2022 American Academy of Neurology Annual Meeting in April.

Regulatory submissions for ULTOMIRISfor the treatment of gMG are currently under review with multiple health authorities, including in the European Union (EU) and Japan.

References

  1. Ultomiris (ravulizumab-cwvz) US prescribing information; 2022.
  2. Anil, R., Kumar, A., Alaparthi, S., Sharma, A., Nye, JL., Roy, B., O’Connor, KC., Nowak, R., (2020). Exploring outcomes and characteristics of myasthenia gravis: Rationale, aims and design of registry – The EXPLORE-MG registry. J Neurol Sci. 2020 Jul 15;414:116830.
  3. Oh SJ., (2009). Muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis current status. Journal of Clinical Neurology. 2009b Jun 1;5(2):53-64.
  4. Tomschik, M., Hilger, E., Rath, J., Mayer, EM., Fahrner, M., Cetin, H., Löscher, W., Zimprich, F., (2020). Subgroup stratification and outcome in recently diagnosed generalized myasthenia gravis. Neurology. 2020 Sep 8;95(10):e1426-e1436.
  5. Hendricks, TM., Bhatti, MT., Hodge, D., Chen, J., (2019). Incidence, Epidemiology, and Transformation of Ocular Myasthenia Gravis: A Population-Based Study. Am J Ophthalmol. 2019 Sep;205:99-105.
  6. Howard, J. F., (2017). Myasthenia gravis: the role of complement at the neuromuscular junction. Annals of The New York Academy of Sciences, 1412(1), 113-128.
  7. Westerberg, E., Punga, A., (2020). Epidemiology of Myasthenia Gravis in Sweden 2006–2016. Brain and behavior. 2020 Nov;10(11):e01819.
  8. Myasthenia Gravis. National Organization for Rare Disorders (NORD). Available here. Accessed March 2022.
  9. Howard, J. F., (2015). Clinical Overview of MG. Available here. Accessed March 2022.
  10. Sanders, D. B., Raja, S. M., Guptill J. T., Hobson-Webb, L. D., Juel, V. C., & Massey, J. M., (2020). The Duke myasthenia gravis clinic registry: I. Description and demographics. Muscle & Nerve, 63(2), 209-216.
  11. Myasthenia Gravis Fact Sheet. (2020, April 27). National Institutes of Neurological Disorders and Stroke. Available here. Accessed March 2022.
  12. Ding, J., Zhao, S., Ren, K., Dang, D., Li, H., Wu, F., Zhang, M., Li, Z., & Guo, J., (2020). Prediction of generalization of ocular myasthenia gravis under immunosuppressive therapy in Northwest China. BMC Neurology, 20(238).
  13. ClinicalTrials.gov. Safety and Efficacy Study of Ravulizumab in Adults With Generalized Myasthenia Gravis. NCT Identifier: NCT03920293. Available here. Accessed March 2022.

Biogen withdraws marketing authorisation application for aducanumab for Alzheimer’s disease

Posted on April 28, 2022 by - Alzheimer's Disease

  • Biogen has informed the European Medicines Agency (EMA) that it is withdrawing its application for marketing authorisation for aducanumab for the treatement of Alzheimer’s disease
  • The EMA had previously found on 16 December 2021 that the benefits of aducanumab did not outweigh its risks and recommended refusing marketing authorisation. Biogen then requested a re-examination.
  • Following Biogen’s discussions with the EMA’s Committee for Medicinal Products for Human Use (CHMP), in which the CHMP indicated that the “data provided thus far would not be sufficient to support a positive opinion”, the company has decided to withdraw the application.
  • It has been 20 years since the last approval of an Alzheimer’s medicine by the EMA.
  • Biogen is set to launch a phase IV trial of aducanumab in May 2022.

On 22 April 2022 Biogen announced that it had notified the European Medicines Agency (EMA) about the withdrawal of its marketing authorisation application for aducanumab for the treatment of early Alzheimer’s disease.

The agency had previously found on 16 December 2021 that the benefits of aducanumab did not outweigh its risks and had therefore recommended refusing marketing authorisation. Biogen requested a re-examination of the EMA’s decision and started discussions with the Agency’s Committee for Medicinal Products for Human Use (CHMP). In its press release issued today, Biogen highlighted that the CHMP had indicated that the “data provided thus far would not be sufficient to support a positive opinion”.

With the last approval of an Alzheimer’s medicine by the EMA dating back to 2002, people living in Europe affected by Alzheimer’s disease have been waiting to gain access to better treatments for 20 years. It will therefore be disappointing news for them to hear that there was insufficient scientific evidence for the EMA to support the authorisation of aducanumab, and that the wait for innovative, disease modifying treatments will have to continue in Europe.

The EMA discussions and the decision by Biogen to withdraw its marketing authorisation application follow developments in the US where the Food and Drug Administration (FDA) chose to grant conditional approval for aducanumab using its “accelerated approval pathway”. This approval was based on aducanumab’s proven effect on lowering amyloid beta, a surrogate endpoint that the FDA deemed “reasonably likely” to predict a clinical benefit to patients.

In its December recommendation, the EMA recognised that aducanumab reduces amyloid beta in the brain, but stated that “the link between this effect and clinical improvement has not been established”. The agency found that the results on cognition and executive function derived from the two phase III clinical trials conducted to date were conflicting, and highlighted potential difficulties in monitoring side effects of the medicine in clinical practice. As a result, the agency concluded that the risk-benefit balance was unfavourable and decided against approval. According to the EMA, “At the time of the withdrawal, while the re-examination was ongoing, the Agency was still of the opinion that the benefits of [aducanmab] did not outweigh its risks.”

https://www.ema.europa.eu/en/medicines/human/withdrawn-applications/aduhelm

Manoj Sivan to deliver keynote lecture at AFRM conference

Posted on April 23, 2022 by - Awards & Appointments, Rehabilitation

The Australasian Faculty of Rehabilitation Medicine has invited Dr Manoj Sivan to deliver the keynote lecture at its conference in Melbourne, Australia on 12 May, 2022. Dr Sivan one of only three UK rehabilitation specialists to have ever been invited to give this prestigious lecture.

The AFRM’s annual keynote lecture was named the George Burniston Oration as part of efforts to showcase its history and pay homage to its founders. Further information about the history of the Oration can be found on the RACP website.