Author: Rachael Hansford

Grant to explore new epilepsy treatment for Tuberous Sclerosis Complex (TSC)

Posted on May 30, 2023 by - Charity, Epilepsy

  • Dr Felix Chan awarded £174k grant to study Tuberous Sclerosis Complex (TSC) and epilepsy by Epilepsy Research UK
  • The new study will investigate lysine metabolism as a therapeutic target for epilepsy in TSC
  • Research designed with TSC and epilepsy patient community through Tuberous Sclerosis Association and Epilepsy Research UK

Dr Felix Chan awarded £174k grant to study Tuberous Sclerosis Complex (TSC) and epilepsy by Epilepsy Research UK. The new study will investigate lysine metabolism as a therapeutic target for epilepsy in TSC Research designed with TSC and epilepsy patient community through Tuberous Sclerosis Association and Epilepsy Research UK.

A researcher based in Aston Institute for Health and Neurodevelopment has been awarded an Endeavour Project Grant of £174,495 by Epilepsy Research UK.  The grant will fund a 36-month study entitled ‘Lysine Metabolism as a therapeutic target for epilepsy in tuberous sclerosis complex (TSC)’. The study will focus on Tuberous Sclerosis Complex (TSC), a rare genetic disease that causes non-cancerous tumours to grow in the brain and other areas of the body. TSC is often accompanied by epilepsy, which affects around 80% of people with the condition. Importantly, epilepsy in TSC is the highest cause of death and remains an unmet clinical need for TSC patients as it is hard to treat with currently available medications.

Dr Felix Chan’s research will investigate the potential of lysine metabolism as a therapeutic target for epilepsy in TSC. This involves understanding how the body processes the amino acid lysine and how it can be manipulated to reduce seizures in people with TSC.  A therapeutic target is a biological molecule, biological pathway or physiological response that is associated with a particular disease process and may be inhibited or activated by a therapy in a way that will change the course of the disease in a positive way.

The study will also involve a PhD studentship to work with Dr Chan, Professor Gavin Woodhall and collaborator Professor Wyatt Yue from Newcastle University, with recruitment for intake expected in October 2023.

Dr Chan’s research project is notable for its collaborative approach. The TSC and epilepsy patient community has been involved in the study design process through collaboration with the Tuberous Sclerosis Association TSC Research Volunteer Network and the Epilepsy Research UK Shape Epilepsy Research Network.

I am delighted to have been awarded this Endeavour Project Grant from Epilepsy Research UK. TSC is a rare genetic disease that affects around one in 6,000 people and can have a profound impact on individuals and their families. My hope is that this research will contribute to the development of new treatments for epilepsy in TSC, improving the lives of those affected by this condition.” Dr Pooja Takhar, joint chief executive of the Tuberous Sclerosis Association, added: “We are pleased to see that the most important voice in TSC – individuals and families living with the condition itself – has been included in the design process of this vital research project. This ensures that the research is focused on the areas that are of most importance to those living with TSC, boosting the potential impact on the lives of people with TSC.”

Dr Felix Chan, lecturer in neuroscience, at Aston University

New government concussion guidance

Posted on May 29, 2023 by - Acquired Brain Injury, Neurology News

New guidelines for recognising and managing concussion in grassroots sports have been published by the Government.

Aimed at the general public and those engaging with sport on a non-professional level, ‘If In Doubt, Sit Them Out’ is guidance with a very clear message that if an individual is suspected of having concussion, they must be immediately removed from play.

Chris Bryant MP, Chair of the All Party Parliamentary Group on Acquired Brain Injury (ABI), and the driving force behind the implementation of the Government’s ABI Strategy, said: “At long last we’re beginning to take this issue seriously. Sport is good for you but a brain injury can completely change your life. I hope every sporting organisation will take these new protocols to heart.”

UKABIF Executive Director Chloe Hayward added: “We welcome this guidance for grassroot sports clubs as it is very much needed to improve understanding and awareness of concussion. It is positive to see the Government taking the first step towards addressing the concerns raised in the DCMS Select Committee Inquiry into concussion in sport in July 2021.”

The guidance, which is aimed at players, coaches, teachers, volunteers, parents and carers, says:

·  No-one should return to competition, training or Physical Education (PE) lessons within 24 hours of a suspected concussion.

·  Anyone suspected of sustaining a concussion should be assessed by an appropriate onsite Healthcare Professional or by contacting the NHS by calling 111 within 24 hours of the injury.

While the guidance is welcomed there are concerns about the implementation of the protocols.

There are still gaps in the guidelines and there are real worries that many healthcare providers are ill equipped to recognise concussion and have little knowledge of managing concussion. We are also disappointed that the protocols do not offer specific advice for women or children – we feel that is a missed opportunity.

Chloe Hayward, UKABIF

“Through the ABI Strategy groups, we will continue to press the Government on fully recognising the dangers of concussion in sports at all levels from grassroots to elite. It is vital that the Government engages with all relevant stakeholders to ensure the best outcomes for anyone with an acquired brain injury.”

The guidance, which has been developed in partnership with medical professionals and sports governing bodies, can be found here.

Eisai submits a marketing authorisation application (MAA) for lecanemab

Posted on May 23, 2023 by - Uncategorised

Eisai has submitted a Marketing Authorisation Application (MAA) for lecanemab, an investigational anti-amyloid beta (Aβ) protofibril antibody, for the treatment of early Alzheimer’s disease (AD) (mild cognitive impairment due to AD and mild AD dementia) with confirmed amyloid pathology in the brain,1 to the Medicines and Healthcare products Regulatory Agency (MHRA) in Great Britain. This investigational treatment has been designated by the MHRA for the Innovative Licensing and Access Pathway (ILAP).2

The MAA is based on the results of the Phase IIb clinical study (Study 201) and Phase III Clarity AD study, which demonstrated that lecanemab treatment showed a reduction of clinical decline in early AD vs placebo at 18 months.1,3 The MAA is subject to a validation to determine whether it will be accepted by the MHRA.

Lecanemab selectively binds and eliminates soluble, toxic Aβ aggregates (protofibrils) that are thought to contribute to the neurotoxicity in AD.1 The Clarity AD study met its primary endpoint and all key secondary endpoints with statistically significant results.1


Submission of our MAA to the MHRA brings us one step closer to bringing a much-needed treatment to an area of significant unmet need. This important milestone follows decades of research and reflects our commitment to alleviate the burden of AD for patients, and their families and carers. We look forward to working with the MHRA over the coming months to support the review of our clinical evidence.

Nick Burgin, Chief Operating Officer and President of Global Value and Access, Eisai EMEA

Eisai serves as the lead of lecanemab development and regulatory submissions globally with both Eisai and Biogen co-commercialising and co-promoting the product and Eisai having final decision-making authority.

References:

  1. van Dyck H et al. Lecanemab in Early Alzheimer’s Disease. New England Journal of Medicine. 2023; 388:9-21.
  2. Eisai. Internal correspondence. 2023.
  3. Swanson C et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimer’s Research and Therapy 2021; 13(80):1-14.

For more information about Eisai in the EMEA region please visit http://www.eisai.eu

Parliamentary ABI reception attracts hundreds of attendees

Posted on May 23, 2023 by - Acquired Brain Injury, Charity, Industry News

UKABIF trustees and members attended an Acquired Brain Injury reception in Parliament hosted by Chris Bryant MP.

Around 60 MPs from across the House attended to hear first hand from people living with an acquired brain injury, just what improvements need to be made. It was a wonderful opportunity for organisations to network and for many constituents living with a brain injury to lobby their MP to call for change.

Chris Bryant, Chair of the All-Party Parliamentary Group on ABI, gave an update on the progress of the Government-wide ABI Strategy which is expected to be published in the summer.

Addressing the reception, Chris Bryant said: “To see so many people come along is amazing. I have been involved in this for a long time and we want to put together a single strategy for the whole of Government on Acquired Brain Injury. In doing so, there is the recognition that there is an issue to deal with as a whole Government.

We have 1.4 million people in the UK, if not more, living with a brain injury and we want anyone, regardless of age or postcode, to be able to live the best life possible

Chris Bryant

“We have 1.4 million people in the UK, if not more, living with a brain injury and we want anyone, regardless of age or postcode, to be able to live the best life possible.”

Chloe Hayward, Executive Director at UKABIF, said: “A huge thank you to everyone who made the journey to attend the reception. The huge response is testament to the will to improve the lives of people living with an ABI. Your voices were heard and we will continue to press for change.”

For further details please contact: Chloe Hayward. T:0345 6080788 M:07903887655. www.ukabif.org.uk

Chris Bryant addressing the reception

THN391 – First in-human dosing in phase 1 trial in Alzheimer’s disease

Posted on May 15, 2023 by - Alzheimer's Disease, Industry News

 Therini Bio Initiates First-In-Human Dosing in Phase 1 Trial of THN391, a Fibrin-Targeting Therapeutic Candidate for Alzheimer’s Disease

THN391 binds to the inflammation-driving component of fibrin that is known to activate pathological immune responses in neurodegenerative and ophthalmologic diseases. Based on preclinical studies to date, targeting this region does not impact or diminish fibrin’s critical role in blood clotting and coagulation. Key safety and proof of mechanism clinical data is expected by the end of 2024.

“Initiating first-in-human dosing for THN391 is a significant milestone and we’re excited about the approach that Therini Bio is taking towards treating Alzheimer’s disease and other inflammatory neurodegenerative and retinal diseases. As an early investor in Therini, we look forward to continue supporting the Company’s mission of developing potential first-in-class therapies targeting toxic fibrin accumulation for areas of significant unmet patient need,” said Laurence Barker, Partner, Dementia Discovery Fund (DDF).

About Therini Bio, Inc.

Therini Bio is a biotech company focused on developing fibrin-targeted therapies to treat inflammatory neurodegenerative and retinal diseases. The Company is developing a pipeline of potential first-in-class therapies targeting toxic fibrin accumulation, for diseases including Alzheimer’s disease (AD), multiple sclerosis (MS), as well as in a variety of retinal diseases, such as diabetic macular edema (DME) where destructive inflammation plays a role in the disease process. The foundational science was licensed based on technology discovered in Katerina Akassoglou, Ph.D. laboratories at the Gladstone Institutes at the University of California San Francisco (UCSF) and formerly the University of California San Diego (UCSD). For more information, visit www.therinibio.com.

Acute migraine treatment accepted for use on NHS in Scotland

Posted on May 10, 2023 by - Headache, Industry News

9th May, 2023: Pfizer Ltd announced that the Scottish Medicines Consortium (SMC) has accepted Vydura ®  (rimegepant) for restricted use for the treatment of acute migraine with or without aura, for patients who have had inadequate symptom relief after trials of at least two triptans or in whom triptans are contraindicated or not tolerated; and have inadequate pain relief with non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol.[i]

Rimegepant is an oral lyophilisate (dissolving wafer) and is the first oral calcitonin gene-related peptide (CGRP) receptor antagonist for the acute treatment of migraine to be accepted for use by the Scottish Medicines Consortium (SMC).

Migraine can be debilitating to those affected,[ii] with one in seven people in the UK living with migraines.2 Migraine most often begins at puberty and most affects those aged between 35 and 45 years.[iii] Migraines are two to three times more common in women, with hormonal changes being a potential trigger.2

Migraines can have a significant impact on the daily lives of people who suffer with them. Today’s decision, to recommend an orally dissolvable wafer and expand migraine treatment options, is a positive step towards helping to improve care for eligible patients in Scotland.

Dr David Watson, Hamilton Medical Group (NHS Grampian)

Migraine can be a severe and painful long-term health condition, with a wide variety of symptoms, often including head pain, vomiting, nausea, disturbed vision, fatigue and sensitivity to light, sound and smells.[iv] Symptoms vary between individuals and attacks and can have a major impact on the lives of those living with migraine, with sufferers often experiencing other long-term mental or physical health conditions.2

Toby Cousens, Head of Hospital and Internal Medicine, Pfizer UK said: “There is an unmet medical need to support people living with migraine and today’s decision is good news for eligible patients in Scotland. As well as the physical impact of symptoms, migraine can have a negative impact on the professional and personal lives of those living with it.  We’re committed to supporting people living with migraine and will continue to work with the SMC and other health bodies in the UK to help further improve access and care.”

It is estimated that up to 43 million workdays are lost each year in the UK to migraine-related absenteeism.2 In addition, estimates state that Migraine may cost the UK economy between £6 billion and £10 billion per year in total healthcare and productivity costs. 2

Pfizer is planning a resubmission to the SMC for the review of rimegepant in the prevention of episodic migraine in adults who have at least four migraine attacks per month, after it was not recommended for use.

[i] Scottish Medicines Consortium (SMC). www.scottishmedicines.org.uk

[ii] The Migraine Trust.  State of the Migraine Nation Dismissed for too long, 2021. Available at: Dismissed-for-too-long_Recommendations-to-improve-migraine-care-in-the-UK.pdf. Accessed: May 2023

[iii] WHO. Headache disorders. Headache disorders (who.int)  Accessed: May 2023

[iv] The Migraine Trust. What is Migraine? Available at: https://migrainetrust.org/understand-migraine/what-ismigraine/#page-section-1 Accessed: May 2023

FDA approves QALSODY™ (tofersen) targeting a genetic cause of ALS

Posted on April 28, 2023 by - Amyotrophic Lateral Sclerosis (ALS)

  • Accelerated approval marks a scientific advancement in treatment of superoxide dismutase 1 (SOD1)-amyotrophic lateral sclerosis (ALS)
  • Approval based on reduction of neurofilament, a biomarker associated with neuronal damage in ALS
  • QALSODY joins SPINRAZA® as Ionis-discovered medicine approved for treatment of a rare and fatal neurodegenerative disease

 25 April 2023: Ionis Pharmaceuticals, Inc today announced that its partner Biogen has received U.S. Food and Drug Administration (FDA) approval of QALSODY™ (tofersen) 100 mg/15mL injection for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. This indication is approved under accelerated approval based on a reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY. Continued approval for this indication may be contingent upon verification of clinical benefit from ongoing trial(s). The ongoing Phase 3 ATLAS study of tofersen in people with presymptomatic SOD1-ALS will serve as the confirmatory study. QALSODY is the first and only approved treatment to target a genetic cause of ALS and the latest Ionis-discovered medicine to gain market approval.

Neurofilaments are proteins that are released from neurons when they are damaged, making them a marker of neurodegeneration.

“Today’s approval of QALSODY represents a scientific advancement for the ALS community. We thank the people with SOD1-ALS whose participation in the clinical studies made this day possible. We are proud of the Ionis scientists whose dedication made the discovery of this medicine possible, and we are appreciative of our partners at Biogen for their ongoing commitment to ALS,” said Brett P. Monia, Ph.D., chief executive officer of Ionis. “The QALSODY approval highlights our significant progress advancing RNA-based treatments targeting severe neurological diseases.” 

Warnings and precautions associated with QALSODY were serious neurologic events, including myelitis and or radiculitis; papilledema and elevated intracranial pressure; and aseptic meningitis. If symptoms consistent with myelitis, radiculitis papilledema, elevated intracranial, or aseptic meningitis develop, diagnostic workup and treatment should be initiated according to the standard of care. Management may require interruption or discontinuation of QALSODY. The most common adverse reactions that occurred in ≥10% of QALSODY treated participants and more than the placebo arm were pain, fatigue, arthralgia, CSF white blood cell increased, and myalgia.

The efficacy of QALSODY was assessed in a 28-week randomized, double-blind, placebo-controlled clinical study in patients 23 to 78 years of age with weakness attributable to ALS and a SOD1 mutation confirmed by a central laboratory. One hundred eight (108) patients were randomized 2:1 to receive treatment with either QALSODY 100 mg (n=72) or placebo (n=36) for 24 weeks (3 loading doses followed by 5 maintenance doses). Concomitant riluzole and/or edaravone use was permitted for patients and at baseline 62% of patients were taking riluzone, and 8% of patients were taking edaravone.

Over 28 weeks in VALOR, participants in the primary analysis population (n=60) treated with QALSODY experienced less decline from baseline as measured by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) compared to placebo, though the results were not statistically significant (QALSODY-placebo adjusted mean difference [95% CI]: 1.2 [-3.2, 5.5]). In the overall intent-to-treat population (n=108), QALSODY-treated participants experienced a 55% reduction in plasma NfL compared to a 12% increase in placebo-treated participants (difference in geometric mean ratios for QALSODY to placebo: 60%; nominal p<0.0001). Additionally, levels of CSF SOD1 protein, an indirect measure of target engagement, were reduced by 35% in the QALSODY-treated group compared to 2% in the corresponding placebo group (difference in geometric mean ratios for QALSODY to placebo: 34%; nominal p<0.0001).

At an interim analysis at 52 weeks of participants who had completed VALOR and enrolled in an open-label extension (OLE) study, reductions in NfL were seen in participants previously receiving placebo and who initiated QALSODY in the OLE, similar to the reductions seen in participants treated with QALSODY in VALOR. Earlier initiation of QALSODY compared to placebo/delayed-start of QALSODY was associated with trends for reduction in decline on measures of clinical function (ALSFRS-R), respiratory strength (slow vital capacity percent-predicted), and muscle strength (hand-held dynamometry megascore), though they were not statistically significant. QALSODY was also associated with a non-statistically significant trend towards reduction of the risk of death or permanent ventilation. These exploratory analyses should be interpreted with caution given the limitations of data collected outside of controlled study, which may be subject to confounding.

The approval of QALSODY was supported by 12-month integrated results from VALOR and its OLE comparing earlier initiation of tofersen (at the start of VALOR) to delayed initiation of tofersen (six months later, in the OLE), that were published in The New England Journal of Medicine.

What is QALSODY?

QALSODY™ (tofersen) is a prescription medicine used to treat adults with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene. This indication is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).

http://www.QALSODY.com.

About QALSODY™ (tofersen)

QALSODY is an antisense oligonucleotide (ASO) designed to bind to SOD1 mRNA to reduce SOD1 protein production. QALSODY is indicated for the treatment of ALS in adults who have a mutation in the SOD1 gene in the U.S. This indication is approved under accelerated approval based on reduction in plasma NfL observed in patients treated with QALSODY. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s). QALSODY is administered intrathecally as three loading doses administered at 14-day intervals followed by maintenance doses administered once every 28 days thereafter. In people with SOD1-ALS, mutations in their SOD1 gene cause their bodies to create a toxic misfolded form of SOD1 protein. This toxic protein causes motor neurons to degenerate, resulting in progressive muscle weakness, loss of function, and eventually, death.

Biogen licensed tofersen from Ionis under a collaborative development and license agreement.

In addition to the ongoing OLE of VALOR, QALSODY is being studied in the Phase 3, randomized, placebo-controlled ATLAS study to evaluate whether QALSODY can delay clinical onset when initiated in presymptomatic individuals with a SOD1 genetic mutation and biomarker evidence of disease activity (elevated plasma NfL). The primary efficacy endpoint is the proportion of participants with emergence of clinically manifest ALS. ATLAS is currently more than 50 percent enrolled with clinical trial sites in 14 countries worldwide with an estimated primary completion date in 2026. More details about ATLAS (NCT04856982) can be found at clinicaltrials.gov.

About Ionis Pharmaceuticals, Inc.

For more than 30 years, Ionis has been a leader in RNA-targeted therapy, pioneering new markets and changing standards of care with its novel antisense technology. Ionis currently has three marketed medicines and a promising late-stage pipeline highlighted by cardiovascular and neurological franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision to become the leader in genetic medicine, utilizing a multi-platform approach to discover, develop and deliver life-transforming therapies.

To learn more about Ionis visit http://www.ionispharma.com

Gene in the brain can reduce anxiety in animal model

Posted on April 27, 2023 by - Industry News

A gene in the brain driving anxiety symptoms has been identified by an international team of scientists. Modification of the gene is shown to reduce anxiety levels, offering a novel drug target for anxiety disorders. The discovery, led by researchers at the Universities of Bristol and Exeter, was published online online on 25th April in Nature Communications.

Severe psychological trauma can trigger genetic, biochemical and morphological changes in neurons in the brain’s amygdala — the brain region implicated in stress-induced anxiety, leading to the onset of anxiety disorders, including panic attacks and post-traumatic stress disorder.

However, the efficacy of currently available anti-anxiety drugs is low with more than half of patients not achieving remission following treatment. Limited success in developing potent anxiolytic (anti-anxiety) drugs is a result of our poor understanding of the neural circuits underlying anxiety and molecular events resulting in stress-related neuropsychiatric states.

In this study, scientists sought to identify the molecular events in the brain that underpin anxiety. They focused on a group of molecules, known as miRNAs in animal models. This important group of molecules, also found in the human brain, regulates multiple target proteins controlling the cellular processes in the amygdala.

Following acute stress, the team found an increased amount of one type of molecule called miR483-5p in a mouse amygdala. Importantly, the team showed that increased miR483-5p suppressed the expression of another gene, Pgap2, which in turn drives changes to neuronal morphology in the brain and behaviour associated with anxiety. Together, the researchers showed that miR-483-5p acts as a molecular brake that offsets stress-induced amygdala changes to promote anxiety relief.

The discovery of a novel amygdala miR483-5p/Pgap2 pathway through which the brain regulates its response to stress is the first stepping stone towards the discovery of novel, more potent and much-needed treatments for anxiety disorders that will enhance this pathway.

Stress can trigger the onset of a number of neuropsychiatric conditions that have their roots in an adverse combination of genetic and environmental factors. While low levels of stress are counterbalanced by the natural capacity of the brain to adjust, severe or prolonged traumatic experiences can overcome the protective mechanisms of stress resilience, leading to the development of pathological conditions such as depression or anxiety.

Dr Valentina Mosienko, one of the study’s lead authors and an MRC Fellow and Lecturer in Neuroscience in Bristol’s School of Physiology, Pharmacology and Neuroscience

“miRNAs are strategically poised to control complex neuropsychiatric conditions such as anxiety. But the molecular and cellular mechanisms they use to regulate stress resilience and susceptibility were until now, largely unknown. The miR483-5p/Pgap2 pathway we identified in this study, activation of which exerts anxiety-reducing effects, offers a huge potential for the development of anti-anxiety therapies for complex psychiatric conditions in humans.”

The research was funded by the Medical Research Council, Academy of Medical Sciences, Leverhulme Trust, Marie Sklodowska-Curie and the Polish National Science Centre.

#AAN2023: Atogepant for preventive treatment of episodic migraine

Posted on April 21, 2023 by - Headache

  • The Phase 3 ELEVATE study demonstrated atogepant is effective and well-tolerated for the preventive treatment of episodic migraine in people who previously failed two to four classes of conventional oral medications used for prevention
  • The trial met its primary and secondary endpoints with results showcasing a significant reduction in mean monthly migraine days for those with episodic migraine taking atogepant 60 mg once daily compared to placebo across a 12-week period

21 April 2023: AbbVie has announced positive data from its Phase 3 ELEVATE study, evaluating atogepant for the preventive treatment of episodic migraine in people who had previously failed two to four classes of oral preventive medications. The results of the study demonstrated adult patients in the atogepant 60 mg once daily (QD) arm experienced a decrease of 4.20 days in their mean monthly migraine days (MMDs) across the 12-week treatment period, which was statistically significantly greater than the 1.85 day reduction observed in the placebo arm (p<0.0001). The data was presented during the Emerging Science session on Tuesday, April 25, at the 2023 American Academy of Neurology (AAN) Annual Meeting taking place in Boston, Massachusetts, US.

“We understand that people living with migraine endure a chronic neurological disease and we are dedicated to providing them the best chance to live a life with less frequent migraines,” said Dawn Carlson, Vice President, Neuroscience Development, AbbVie. “The data presented at AAN underscores the important role of atogepant, not only as a treatment option for people living with episodic migraine but also for those whose previous treatments failed to help reduce the impact of migraine on their lives.”

The ELEVATE study met all primary and secondary endpoints and demonstrated a statistically significant reduction in MMDs for those with episodic migraine taking atogepant 60 mg QD compared to placebo. The primary endpoint was the change from baseline in mean MMDs across 12 weeks and the secondary endpoints included achievement of more than 50% reduction in MMDs, change from baseline in MMDs, and change from baseline in acute medication use days across 12 weeks.

A total of 309 participants were enrolled and of these participants, 56% had previously failed two classes of oral migraine preventive medications and 44% had previous failed three or more classes, having discontinued them due to concerns with efficacy or tolerability. The results demonstrated atogepant 60 mg QD was well tolerated and the safety results were consistent with the known safety profile of atogepant. The most commonly reported (≥5% in any treatment arm) treatment-emergent adverse events (atogepant vs placebo, respectively) included constipation (10.3% vs 2.5%), COVID-19 (8.3% vs 9.6%), nausea (7.1% vs 3.2%), and nasopharyngitis (5.1% vs 7.6%).

“For those living with migraine, the path towards effective treatment can be a long and complex journey,” said Prof. Patricia Pozo-Rosich, MD, PhD, Head of Neurology Section, Vall d’Hebron Hospital and Institute of Research, Spain. “The ELEVATE trial demonstrates atogepant as a once-daily oral treatment that can significantly reduce monthly migraine days across a lifelong disorder, allowing people to experience relief in their daily lives, including those who have previously been failed by other preventive migraine treatments.”

The U.S. Food and Drug Administration recently approved QULIPTA® as the first and only oral calcitonin gene-related peptide (CGRP) receptor antagonist proven to prevent both episodic and chronic migraine in adults in the United States. AbbVie will continue to pursue regulatory submissions for atogepant across international markets throughout the year.

About the ELEVATE Study
The ELEVATE study was a global, randomised, double-blind, placebo-controlled trial assessing the safety, tolerability, and efficacy of atogepant 60 mg once daily (QD) compared with placebo for the preventive treatment of episodic migraine in adult participants who previously failed two to four classes of oral prophylactic treatments. The primary endpoint was the change from baseline in mean monthly migraine days (MMDs) across 12 weeks. Secondary endpoints included achievement of more than 50% reduction in MMDs, change from baseline in MMDs, and change from baseline in acute medication use days across 12 weeks. More information can be found on http://www.clinicaltrials.gov (NCT04740827). 

About Atogepant (QULIPTA®)
Atogepant is an orally administered, CGRP receptor antagonist specifically developed for the preventive treatment of migraine in adults. CGRP and its receptors are expressed in regions of the nervous system associated with migraine pathophysiology. Studies have shown that CGRP levels are elevated during migraine attacks and selective CGRP receptor antagonists confer clinical benefit in migraine. The use of atogepant in migraine is not approved in the United Kingdom or European Union and its safety and efficacy have not been evaluated.