H. Lundbeck A/S (Lundbeck) announces that the results from the DELIVER study have been recognized for their importance for the scientific and medical community. The results from the clinical study with VYEPTI® (eptinezumab-jjmr) were accepted for publication in the prestigious journal Lancet Neurology, one of the most cited medical journals within neurology. The DELIVER study results were published online on June 15, and the full paper can be accessed here: Lancet (thelancet.com).
Dr. Johan Luthman, EVP and Head of Research & Development in Lundbeck, said:
“We are incredibly proud that our clinical research is recognized by the medical and scientific community. The publication of the DELIVER results by Lancet Neurology is a clear indication that Lundbeck performs clinical research of the highest quality, and that the results of these efforts are relevant to both clinicians and patients.”
The DELIVER study investigated the efficacy and safety of Vyepti 100 mg and 300 mg IV infusion in patients with two to four documented unsuccessful prior preventive treatment failures in the past 10 years, with at least two of the treatment failures being older oral preventive therapies (including: propranolol, metoprolol, topiramate, amitriptyline, flunarizine, valproate, divalproex, candesartan) or botulinum toxin A/B (if documented that botulinum toxin was used for chronic migraine), and at least one failure being due to inadequate efficacy. The DELIVER study met its primary endpoint of demonstrating statistically significant superiority of Vyepti versus placebo in reducing the number of monthly migraine days (MMDs) over 12 weeks of treatment and it also achieved statistical significance on all key secondary outcome measures.
The safety profile of Vyepti observed in the DELIVER study was consistent with the safety profile observed in the pivotal phase III studies with Vyepti for the preventive treatment of migraine.
“These results contribute to the expanding body of evidence in support of migraine preventive treatments with anti-CGRP monoclonal antibodies in patients with previous preventive treatment failures to traditional oral medication. The key message from the study results, which is relevant for both physicians and patients, is that even after multiple treatment failures, there is still hope that patients can respond to this new class of anti-CGRP treatments”, says, Dr. Messoud Ashina, Professor of Neurology, and lead author on the DELIVER publication.
DELIVER (NCT04418765) is a phase lllb, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of Vyepti in patients with chronic or episodic migraine. Chronic migraine was defined as migraine occurring on ≥8 days per month and headache occurring on >14 days, and episodic migraine as migraine occurring on ≥4 days and headache occurring on ≤14 days. All patients had to have experienced failures of two to four prior preventive treatment classes (including: propranolol, metoprolol, topiramate, amitriptyline, flunarizine, valproate, divalproex, candesartan) or botulinum toxin A/B (if documented that botulinum toxin was used for chronic migraine), and at least one failure being due to inadequate efficacy. Patients who experienced failure on a previous treatment targeting the calcitonin gene-related peptide (CGRP) pathway were excluded from participation. Documented evidence of prior migraine treatment failures was supported by medical records or by physicians´ confirmation specific to each treatment in the past 10 years.
In the study, 892 patients were randomized to receive eptinezumab 100 mg or 300 mg or placebo by intravenous (IV) infusion. Patients included in the study most frequently experienced treatment failures of topiramate and amitriptyline, with 550(61.8%), 277(31.1%), and 60(6.7%) patients experiencing 2, 3, and 4 prior preventive treatment failures respectively. The primary endpoint was change from baseline in the number of monthly migraine days over Weeks 1-12. Key secondary endpoints included response rates as patients with 50% or greater reduction from baseline in MMDs (Weeks 1-12), response rates of patients with 75% or greater reduction from baseline in MMDs (Weeks 1-12) and change from baseline in the number of MMDs (Weeks 13-24). Other secondary endpoints assessed the effect of Vyepti vs placebo on: 6-item Headache Impact test score (HIT-6), Migraine-specific quality of life (MSQ v2.1), HRQoL (EQ-5D-5L) visual analogue scale (VAS) score, Health care resources utilization (HCRU), and Work Productivity and Activity Impairment Questionnaire (WPAI).
The safety and tolerability of Vyepti in the DELIVER study were similar to placebo and consistent with findings from previous Vyepti clinical trials. In DELIVER and earlier Vyepti studies, upper respiratory tract infection, nasopharyngitis, dizziness, and fatigue were the most commonly reported treatment-emergent adverse events (TEAEs).
Vyepti is a humanized monoclonal antibody that binds to CGRP which was purposefully developed for IV administration. The efficacy and safety of Vyepti was evaluated in two phase III clinical trials (PROMISE-1 in episodic migraine[iv] and PROMISE-2 in chronic migraine[v]), where Vyepti met its primary endpoint of decrease in MMDs over weeks 1-12 in both episodic and chronic migraine. Furthermore, the clinical trial program demonstrated a treatment benefit over placebo that was observed for both doses of Vyepti as early as day 1 post-infusion. For the initial approval, the safety of Vyepti was evaluated in 2,076 adult patients with migraine who received at least one dose of Vyepti. 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. In PROMISE-1 and PROMISE-2, 1.9% of patients treated with Vyepti discontinued treatment due to adverse reactions.
Vyepti was approved by the U.S. Food and Drug Administration (FDA) for the preventive treatment of migraine in adults in February 2020 and it is launched in the U.S. market. In January 2022, Vyepti was granted marketing authorization by the European Medicines Agency (EMA) and is expected to be launched in the first European countries over the coming months.
Migraine is a complex and incapacitating neurological disease characterized by recurrent episodes of severe headaches typically accompanied by an array of symptoms, including nausea, vomiting, and sensitivity to light or sound[vi]. It is estimated to affect approximately 39 million people in the U.S. and more than 1 billion worldwide and impacts three times as many women than men. Migraine is the second leading cause of years lived with disability (YLD) among all diseases, and it is the top YLD cause among patients aged 15 to 49 years, according to the Global Burden of Disease study[vii]. Not only is headache painful, but migraine also imposes both a social and financial burden. In Europe, migraine alone affects close to 50 million people costing the economy EUR 18 billion annually according to the Cost of Brain Disorders in Europe[viii] study and this is without the indirect cost associated with presenteeism (i.e., productivity losses due to reduced efficiency of persons who are not sufficiently ill to be absent from work). Repeated headache attacks, and often the constant fear of the next one, damage family life, social life and work life. Furthermore, frequent use of acute migraine treatments may leave patients experiencing, or at risk of developing, medication overuse headache.
Indication and Important Safety Information
VYEPTI (eptinezumab-jjmr) is indicated for the preventive treatment of migraine in adults.
Important Safety Information
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, and rash, have occurred with VYEPTI in clinical trials. 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.
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.
Thomas Mikkel Mortensen
Media Relations Lead, Corp. Communication
+45 30 83 30 24
Palle Holm Olesen
Vice President, Investor Relations
+45 30 83 24 26
H. Lundbeck A/S (LUN.CO, LUN DC, HLUYY) is a global pharmaceutical company specialized in brain diseases. For more than 70 years, we have been at the forefront of neuroscience research. We are tirelessly dedicated to restoring brain health, so every person can be their best.
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 5,300 employees in more than 50 countries, 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 generated revenue of DKK 16.3 billion in 2021 (EUR 2.2 billion; USD 2.6 billion).
[i] Reuter U, Goadsby LJ, Lanteri-Minet M, et al. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet 2018;392: 2280–7
[ii] Ferrari MD, Diener HC, Ning X, et al. Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial. Lancet 2019;394
[iii] Mulleners WM, Kim B, Lainez MJA, et al. Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial Lancet Neurol 2020;19:814-825.
[iv] Ashina M, McAllister P, Cady R, Hirman J, Ettrup A. Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1). Cephalalgia. 2020; 40(3):241-254
[v] Lipton RB, Goadsby PJ, Smith J, Schaeffler BA, et al. Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology. 2020; 94(13):e1365-e1377
[vi] Villalón CM. The role of CGRP in the pathophysiology of migraine and efficacy of CGRP receptor antagonists as acute antimigraine drugs. Pharmacol Ther. 2009;124(3):309-323
[vii] Steiner TJ, Jensen R, Katsarava Z, et al. Migraine is first cause of disability in under 50s: will health politicians now take notice? J Headache Pain. 2018;19(1):17. [viii] Gustavsson A, Svensson M, Jacobi F, et al. Cost of disorders of the brain in Europe.
2010 [published correction appears in Eur Neuropsychopharmacol. 2012 Mar;22(3):237-8. den Bergh, Peter Van [corrected to Van den Bergh, Peter]]. Eur Neuropsychopharmacol. 2011 Oct;21(10):718-79.