Lundbeck to Present a Breadth of Migraine and Cluster Headache Data at the 66th Annual Scientific Meeting of the American Headache Society

Lundbeck US, the US subsidiaries of H. Lundbeck A/S, today announced 11 data presentations at the 66^th Annual Scientific Meeting of the American Headache Society (AHS) taking place in San Diego, Calif., June 13-16, 2024. These abstracts will be featured in two oral and nine poster presentations and include new analyses of clinical data and real-world studies of VYEPTI^® (eptinezumab-jjmr), an anti-CGRP monoclonal antibody for the preventive treatment of migraine. The company is also sponsoring a symposium, "Beyond Headache Days: Implications of real-world anti-CGRP findings and advancing migraine research," on June 15 at 12:30 p.m. PT featuring findings from the real-world observational REVIEW study.

VYEPTI is indicated for the preventive treatment of migraine in adults. VYEPTI is contraindicated in patients with serious hypersensitivity to eptinezumab-jjmr or to any of its ingredients. Reactions have included anaphylaxis and angioedema. Please see Important Safety Information below.

Phase 3 post hoc analyses explore the extent of monthly headache day (MHD) reduction and the overlay of MHDs and pain severity 
PREVAIL was an open-label phase 3 trial, which evaluated the long-term safety of VYEPTI in 128 patients with chronic migraine. No new safety signals were identified during the study. The impact of VYEPTI on patient-reported outcomes was also evaluated. A post-hoc analysis of the PREVAIL study evaluated the impact of long-term VYEPTI treatment on MIDAS-derived headache frequency, severity, and associated disability. Post-hoc analysis showed that the majority of patients achieved less than four MHDs, a potential indicator of preventive treatment optimization, including an increase in patients reporting zero MHDs from Week 12 to Week 104. Furthermore, overlaying MHD frequency and pain severity showed a 60% decrease in frequency-severity index (FSI) score, from baseline (11.4) to week 12 (3.5) which was sustained to week 104.¹

"To help improve quality of life for people living with migraine, treatment goals should be discussed," said Dr. Amaal Starling, Neurologist, Mayo Clinic. "These results underline the complexity of migraine and the benefit of individualizing goals based on the patient's lifestyle and personal needs. In addition to reducing headache frequency to less than four monthly headache days in most patients, there was also a reduction in headache severity and related disability in the Phase 3 PREVAIL study."

Interictal periods between headache days are important for improvements in headache-related life impact 
It has been hypothesized that longer periods between headache episodes, known as interictal periods, provide more time for the nervous system to reset from the previous episode, potentially improving disease status and health-related quality of life. In a new post-hoc analysis from the Phase 3 PROMISE-2 study of VYEPTI for migraine prevention in adults with chronic migraine, longer interictal periods between headache were associated with positive changes in patient-reported outcome measures assessed by the Headache Impact Test (HIT-6) total score, Patient Global Impression of Change (PGIC) rating, and patient-identified most bothersome symptom (PI-MBS) rating.²

Real world endpoints capture clinically meaningful impact of chronic migraine beyond monthly headache days 
The findings from Real-world Evidence and Insights into Experiences With eptinezumab-jjmr (REVIEW), an observational study recently published in The Journal of Headache and Pain, revealed the mean number of self-reported "good days" per month more than doubled (increased from 8 to 18) after VYEPTI treatment.³ The study did not define the definition of "good" days. It is associated with VYEPTI and migraine as described by the patient. Additionally, 80% of participants reported ever experiencing brain fog (a symptom of migraine defined as feeling confused, having difficulty learning or remembering, or having trouble speaking or reading.) associated with migraine and 86% reported some level of improvement in their brain fog symptoms after VYEPTI. Furthermore, post-hoc analyses found an association between increased "good" days and degree of improvement in brain fog associated with migraine.⁴ Lastly, patients reported an increase of approximately 10 "good" days per month after VYEPTI, regardless of the presence or absence of psychiatric comorbidities and regardless of previous exposure to subcutaneous anti-CGRP treatment.⁵ The REVIEW study used a retrospective chart review, patient survey and physician interview to assess real-world experiences among 94 patients with chronic migraine who had received at least two doses of VYEPTI in the clinical setting. Data reported are from the patient survey.³

"We at Lundbeck strive to advance the treatment paradigm by better understanding the holistic impact of migraine. We are excited to present data highlighting the importance of longer interictal periods as well as migraine associated cognition ? two areas which are particularly meaningful to people living with this disease," said Damian Fiore, Vice President, Lundbeck US Medical Affairs Neurology.

Investigational trials explore unmet needs in cluster headache 
Steward J. Tepper, MD, will deliver an oral presentation on the efficacy and safety of eptinezumab-jjmr in patients with episodic cluster headache (ALLEVIATE).⁶ Additionally, a poster presentation will showcase data on the long-term safety, tolerability, and effectiveness of eptinezumab-jjmr in patients with chronic cluster headache (CHRONICLE).⁷ Eptinezumab-jjmr is not approved for use in cluster headache.

Following is a full list of Lundbeck presentations at AHS 2024, including new data on the impact of perceived stigma on people living with migraine, which will be featured in an oral session:

• P-644: Long-term reductions in headache frequency, severity, and disability in patients with chronic migraine treated with eptinezumab: post hoc analyses of the PREVAIL study¹
• P-622: Headache-related life impact and patient-perceived disease improvement by length of interictal period between headache/migraine: A post hoc analysis of PROMISE-2²
• P-601: Patients with chronic migraine treated with eptinezumab reported improvements in brain fog and the number of good days per month in a real-world setting⁴
• P-600: Impact of psychiatric conditions on the real-world effectiveness of eptinezumab treatment in patients with chronic migraine⁵
• IOR-01 presented by Steward J. Tepper, MD, on Saturday, June 15 at 8 a.m. PT: Efficacy and safety of eptinezumab in patients with episodic cluster headache (ALLEVIATE): A randomized placebo-controlled trial⁶
• P-632: Long-term safety, tolerability, and effectiveness of eptinezumab in patients with chronic cluster headache (CHRONICLE): An open-label safety study⁷
• IOR-07 presented by Dawn C. Buse, PhD, on Saturday, June 15 at 9 a.m. PT: Sources and impact of perceived stigma among people with migraine: Insights from the mixed-method Migraine Community Survey⁸
• P-602: Real-world effectiveness of intravenous eptinezumab in patients with chronic migraine and previous subcutaneous preventive migraine treatment⁹
• P-603: Long-term maintenance of ?50% migraine response with eptinezumab treatment in patients with 2?4 prior preventive migraine treatment failures¹⁰
• P-621: Preventive migraine treatment optimization and shifts in headache frequency with eptinezumab: DELIVER post hoc analysis¹¹
• P-511: Person-centric communications in migraine: Delphi-like consensus on best practice recommendations for people with migraine and healthcare professionals¹²

About VYEPTI^® 
VYEPTI^® (eptinezumab-jjmr) is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor. VYEPTI was deliberately developed for administration by IV infusion to deliver 100 percent of the medication into the bloodstream at the end of the infusion.

The efficacy and safety of VYEPTI were demonstrated in two phase 3 clinical trials; episodic migraine in PROMISE-1 and chronic migraine in PROMISE-2. VYEPTI met its primary endpoint of decrease in mean monthly migraine days (MMD) over months 1-3 in both episodic and chronic migraine. The safety of VYEPTI was evaluated in 2,076 patients with migraine who received at least one dose of VYEPTI. The most common adverse reactions (?2 percent and at least 2 percent or greater than placebo) in the clinical trials for the preventive treatment of migraine were nasopharyngitis and hypersensitivity. In PROMISE-1 and PROMISE-2, 1.9 percent of patients treated with VYEPTI discontinued treatment due to adverse reactions.

VYEPTI offers patients with migraine a preventive treatment administered as one 30-minute IV infusion 4 times a year (every three months). The recommended dosage is 100 mg, and some patients may benefit from a dosage of 300 mg. Dosing should be based on the guidance in the Prescribing Information and Patient Information.

Indication 
VYEPTI^® (eptinezumab-jjmr) is indicated for the preventive treatment of migraine in adults.

Important Safety Information

CONTRAINDICATIONS
VYEPTI is contraindicated in patients with serious hypersensitivity to eptinezumab-jjmr or to any of the excipients. Reactions have included anaphylaxis and angioedema.

WARNINGS AND PRECAUTIONS
Hypersensitivity reactions: Hypersensitivity reactions, including angioedema, urticaria, facial flushing, dyspnea, and rash, have occurred with VYEPTI in clinical trials and in the postmarketing setting. Most hypersensitivity reactions occurred during infusion and were not serious, but often led to discontinuation or required treatment. Serious hypersensitivity reactions may occur. Cases of anaphylaxis have been reported in the postmarketing setting. If a hypersensitivity reaction occurs, consider discontinuing VYEPTI, and institute appropriate therapy.

ADVERSE REACTIONS
The most common adverse reactions (?2% and at least 2% or greater than placebo) in the clinical trials for the preventive treatment of migraine were nasopharyngitis and hypersensitivity.

VYEPTI was approved by the U.S. Food and Drug Administration (FDA) for the preventive treatment of migraine in adults in February 2020. For more information, please see Full Prescribing Information and Patient Information or visit www.VYEPTIHCP.com.

About Migraine
Migraine is a complex and disabling neurological disorder that limits functionality and quality of life.¹³ It is characterized by moderate to severe head pain typically accompanied by an array of symptoms, including nausea, vomiting and sensitivity to light or sound.^{13, 14} Over time, migraine may worsen, with attacks increasing in frequency, severity and duration.^{15, 16} It is estimated to affect approximately 39 million people in the U.S. and impacts three times as many women than men.¹³ It is the second leading cause of years lived with disability (YLD) among all diseases and is the top YLD cause among people aged 15 to 49 years, according to the Global Burden of Disease study.¹⁷ The impact of migraine permeates into career, home life and relationships.¹⁸

About PREVAIL study
PREVAIL was a Phase 3, open-label multi-site U.S.-based study that evaluated eptinezumab 300 mg intravenous administration in 128 adults with chronic migraine (CM). PREVAIL included two treatment phases: the primary treatment phase included four infusions of eptinezumab 12 weeks apart (Day 0, and Weeks 12, 24, and 36); the secondary treatment phase included up to four additional eptinezumab infusions 12 weeks apart (Weeks 48, 60, 72, and 84). Further, patients were followed for 20 additional weeks after the final infusion until Week 104. The PREVAIL study evaluated the long-term safety of repeat doses of eptinezumab in patients with CM, as well as the pharmacokinetics, immunogenicity, and impact of eptinezumab on patient-reported outcomes (PROs). Patient-reported outcome measures included the Migraine Disability Assessment (MIDAS) questionnaire, patient-identified most bothersome symptom (PI-MBS) associated with migraine, Patient Global Impression of Change (PGIC), and 6-item Headache Impact Test (HIT-6).

About Cluster Headache
Cluster headache (CH) is a rare and debilitating disease affecting 1 in a thousand and impacts approximately 2.5 times as many men than women. CH is characterized by severe and strictly unilateral headaches that are associated with autonomic symptoms on the same side. The attacks occur in bouts, composed of series of 15?180-minute attacks of excruciating pain occurring near-daily to multiple times daily for weeks to months, with remissions of months to years. CH can be classified as either episodic or chronic based on the presence or absence of remission periods >3 months.¹⁹ Episodic cluster headache (eCH) is characterized by attack-free remission periods of ?3 months.²⁰ Hallmarks of chronic CH (cCH) are continuous cluster periods which last for ?1 year, without a remission period or with remission periods of <3 months. cCH is less common than episodic CH (accounting for 20% of all cases of CH) but is associated with a greater disease burden and higher costs than episodic CH.^21,22

About ALLEVIATE and CHRONICLE
ALLEVIATE (NCT04688775) was an interventional, multi-region, randomized, double-blind, placebo-controlled, delayed-start study. Adults (n=231) with eCH (based on the International Classification of Headache Disorders, 3^rd edition) and a history of cluster period(s) lasting ?6 weeks were randomized (1:1 ratio) to one of two initial treatments: eptinezumab 400 mg (n=113) or placebo (n=118), administered intravenously. Patients initially receiving placebo received eptinezumab 400 mg at Week 4 and vice versa. The primary endpoint was the change from baseline in the number of weekly attacks over Weeks 1?2. Additional endpoints included ?50% reduction from baseline in the number of weekly attacks and Patient Global Impression of Change (PGIC) score (from 1=very much improved to 7=very much worse).

CHRONICLE (NCT05064397) was an interventional, open-label, fixed-dose, multiple administration study to evaluate long term treatment of eptinezumab in adults with a documented history of cCH according to the International Classification of Headache Disorders. Eligible patients (n=131) received up to 4 intravenous infusions of eptinezumab 400 mg at 12-week intervals. The primary objective was to evaluate the long-term safety and tolerability of eptinezumab in patients with cCH. The secondary objective was to assess the clinical effectiveness of eptinezumab in patients with cCH.

About Lundbeck
Lundbeck Pharmaceuticals LLC is a wholly owned US subsidiary of H. Lundbeck A/S (HLUNa / HLUNb, HLUNA DC / HLUNB DC), a global biopharmaceutical company focused exclusively on neuroscience, with more than 70 years of experience in improving the lives of people with neurological and psychiatric diseases.

As a focused innovator, we strive for our research and development programs to tackle some of the most complex challenges. We develop transformative medicines targeting people for whom there are few, if any, treatment options. Our goal is to create long term value and make a positive contribution to people and societies, everywhere we operate. We are committed to fighting stigma and discrimination, and we act to improve health equity for the people we serve and the communities we are part of.

Too many people worldwide live with brain diseases ? complex conditions often invisible to others that nonetheless take a tremendous toll on individuals, families and societies. We are committed to fighting stigma and discrimination against people living with brain diseases and advocating for broader social acceptance of people with brain health conditions. Every day, we strive for improved treatment and a better life for people living with brain disease.

We have approximately 5,700 employees, and our products are available in more than 100 countries. Our research programs tackle some of the most complex challenges in neuroscience, and our pipeline is focused on bringing forward transformative treatments for brain diseases for which there are few, if any therapeutic options. We have research facilities in Denmark and the United States, and our production facilities are located in Denmark, France, and Italy.

Lundbeck US comprises the wholly owned US subsidiaries of H. Lundbeck A/S, including Lundbeck LLC and Lundbeck Pharmaceuticals LLC. With a workforce of more than 1,000 colleagues, Lundbeck US is deeply committed to enhancing the lives of patients, families, and caregivers through focused innovation in neuroscience. For additional information, please visit Lundbeck.com/us and connect with us on LinkedIn and X at @LundbeckUS.

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1} Blumenfeld A, Starling AJ, Kudrow D, et al. Long-term reductions in headache frequency, severity, and disability in patients with chronic migraine treated with eptinezumab: post hoc analyses of the PREVAIL study. Available at https://doi.org/10.1111/head.14716. Accessed May 8, 2024.
² Tepper SJ, Diamond ML, Hirman J, et al. Headache-related life impact and patient-perceived disease improvement by length of interictal period between headache/migraine: A post hoc analysis of PROMISE-2. Available at https://doi.org/10.1111/head.14716. Accessed May 8, 2024.
³ Argoff C, Herzog SP, Smith RM, et al. Real-world effectiveness and satisfaction with intravenous eptinezumab treatment in patients with chronic migraine: REVIEW, an observational, multi-site, US-based study. J Headache Pain 25, 65 (2024). https://doi.org/10.1186/s10194-024-01764-9
⁴ Buse DC, Soni-Brahmbhatt S, Asher D, et al. Treatment with eptinezumab reduces "brain fog" and increases the number of good days per month in patients with chronic migraine in a real-world setting. Available at https://doi.org/10.1111/head.14716. Accessed May 8, 2024.
⁵ Argoff C, Herzog SP, Smith RM, et al. Impact of psychiatric conditions on the real-world effectiveness of eptinezumab treatment in patients with chronic migraine. Available at https://doi.org/10.1111/head.14716. Accessed May 8, 2024.
⁶ Jensen, RH., Tepper, SJ., Charles, AC., et al., Efficacy and safety of eptinezumab in patients with episodic cluster headache (ALLEVIATE): A randomized placebo-controlled trial. Available at https://doi.org/10.1111/head.14716. Accessed May 8, 2024.
⁷ Tassorelli, C., Goadsby, PJ., Charles, AC., et al. Long-term safety, tolerability, and effectiveness of eptinezumab in patients with chronic cluster headache (CHRONICLE): An open-label safety study. Available at https://doi.org/10.1111/head.14716. Accessed May 8, 2024.
⁸ Buse DC, Torre E, Marcos IC, et al. Sources and impact of perceived stigma among people with migraine: Insights from the mixed-method Migraine Community Survey. Available at https://doi.org/10.1111/head.14716. Accessed May 8, 2024.
⁹ Argoff C, Herzog SP, Smith RM, et al. Real-world effectiveness of intravenous eptinezumab in patients with chronic migraine and previous subcutaneous preventive migraine treatment. Available at https://doi.org/10.1111/head.14716. Accessed May 8, 2024.
¹⁰ Ailani J, Soni-Brahmbhatt S, Awad SF, et al. Long-term maintenance of ?50% migraine response with eptinezumab treatment in patients with 2?4 prior preventive migraine treatment failures. Available at https://doi.org/10.1111/head.14716. Accessed May 8, 2024.
¹¹ Tassorelli C, Starling AJ, Awad SF, et al. Preventive migraine treatment optimization and shifts in headache frequency with eptinezumab: DELIVER post hoc analysis. Available at https://doi.org/10.1111/head.14716. Accessed May 8, 2024.
¹² Buse DC, Coe J, Duyvejonck A, et al. Person-centric communications in migraine: Delphi-like consensus on best practice recommendations for people with migraine and healthcare professionals. Available at https://doi.org/10.1111/head.14716. Accessed May 8, 2024.
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¹⁴ National Institute of Neurological Disorders and Stroke. Migraine. Available at: https://www.ninds.nih.gov/health-information/disorders/migraine. Accessed March 28, 2024.
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¹⁹ Kandel SA, Mandiga P. Cluster Headache. StatPearls. Treasure Island (FL); 2024.
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²¹ Schindler EAD, Burish MJ. Recent advances in the diagnosis and management of cluster headache. BMJ 2022; 376: e059577.
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