H. Lundbeck A/S (Lundbeck) today announced positive results from the RESOLUTION trial. This trial randomized 608 patients with a dual diagnosis of chronic migraine (CM) and medication-overuse headache (MOH) to receive an infusion of either Vyepti 100 mg or placebo. The RESOLUTION trial evaluated the efficacy of Vyepti versus placebo as add-on to a brief educational intervention for the prevention of migraine. Vyepti met the primary endpoint, showing statistically significant greater monthly migraine day (MMD) reductions during weeks 1 to 4 with Vyepti, compared to placebo. From a baseline average of 21 days, the change from baseline in MMDs were -6.9 with Vyepti treatment compared to -3.7 days for placebo (p<0.0001).

In addition to the notable reductions in MMDs, significantly greater proportions of patients no longer met the diagnostic criteria for CM or MOH after treatment with Vyepti vs placebo. The RESOLUTION trial results also confirmed the early onset of Vyepti's efficacy, with significant reductions in pain severity and acute medication use, both indicating important benefits for patients impacted by severe migraine.

"In the RESOLUTION trial, we boldly added patient education, which in itself is a recognized therapeutic strategy for patients with chronic migraine and medication overuse headache, to the IV infusion. Yet, we still see robust efficacy of Vyepti, so we are very pleased with the results. These results underscore Vyepti's efficacy, while highlighting its potential to rapidly improve the lives of people living with severe migraine," said Johan Luthman, EVP, and Head of Research & Development at Lundbeck.

"These results are good news for our patients with migraine complicated by medication overuse. And indeed, a large proportion of the patients seeking our care for high-frequency or chronic migraine are also burdened by the consequences of taking too much medication, only to experience that the acute medication works less well over time and actually aggravate the migraine. These are among the patients in need of novel, migraine specific anti-CGRP treatments to prevent migraine attacks.", said Dr. Rigmor Højland Jensen, Professor at University of Copenhagen, Director of the Danish Headache Center, and lead investigator on the RESOLUTION trial.

About the RESOLUTION trial
The RESOLUTION trial was a phase IV, multi-national, randomized, double-blind, placebo-controlled trial[i]. The trial enrolled 608 participants with dual diagnoses of chronic migraine and MOH, and participants were randomly allocated to one of two treatment groups, brief educational intervention (BEI) and eptinezumab (100 mg; n = 305) or BEI and placebo (n = 303), in a 1:1 ratio. BEI involves a short screening followed by individual feedback on how and why acute migraine medication use should be reduced, and this approach to patient education has been shown to result in long-term medication reductions for patients with MOH. RESOLUTION is the first randomized controlled trial to assess the efficacy of an anti-CGRP treatment in combination with structured patient education in chronic migraine and MOH. The primary endpoint was the change from baseline in monthly migraine days over weeks 1-4. Secondary and exploratory endpoints assessed monthly migraine days over weeks 1-12, MOH remission, transition from chronic to episodic migraine, health-related quality of life, work productivity, and the safety and tolerability of eptinezumab in this patient population. The participants in the RESOLUTION trial were mainly included from European countries.

About Vyepti® (eptinezumab)
Vyepti is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) which was intentionally designed for IV administration. The efficacy and safety of Vyepti was evaluated in two phase III clinical trials (PROMISE-1 in episodic migraine[ii] and PROMISE-2 in chronic migraine[iii]), 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. The safety of Vyepti was evaluated in more than 2,000 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® (eptinezumab-jjmr) was approved by the U.S. Food and Drug Administration (FDA) for the preventive treatment of migraine in adults in February 2020, and in January 2022, Vyepti was granted European marketing authorization approval. Today, Vyepti® is launched in over 30 markets globally.

About migraine and medication-overuse headache (MOH)
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[iv]. 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[v]. As the most prevalent neurological disorder in people aged <50 years, migraine 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[vi] 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 migraine attacks, and often the constant fear of the next one, damage family life, social life, and work life. Furthermore, increased use of acute headache medications may lead to central sensitization and decreased effectiveness of the acute headache medication, resulting in a vicious cycle of increased number of headache days requiring even further increased amounts of acute headache medication. Without proper migraine management, this process results in worsening migraine, and may lead to the development of chronic migraine and MOH [vii]. The secondary headache of MOH is a common complication among individuals with primary headache disorders like chronic migraine.

Contacts

About H. Lundbeck A/S
Lundbeck is a biopharmaceutical company focusing exclusively on brain health. With more than 70 years of experience in neuroscience, we are committed to improving the lives of people with neurological and psychiatric diseases.

Brain disorders affect a large part of the world's population, and the effects are felt throughout society. With the rapidly improving understanding of the biology of the brain, we hold ourselves accountable for advancing brain health by curiously exploring new opportunities for treatments.

As a focused innovator, we strive for our research and development programs to tackle some of the most complex neurological challenges. We develop transformative medicines targeting people for whom there are few or no treatments available, expanding into neuro-specialty and neuro-rare from our strong legacy within psychiatry and neurology.

We are committed to fighting stigma and we act to improve health equity. We strive to create long-term value for our shareholders by making a positive contribution to patients, their families and society as a whole.

Lundbeck has about 5,500 employees in over 50 countries, and our products are available in over 80 countries. For additional information, we encourage you to visit our corporate site www.lundbeck.com and connect with us via LinkedIn.

References
[i] Jensen RH, et al. Front. Neurol. 2023; 14:1114654.

[ii]Ashina M, et al. Cephalalgia. 2020 Mar;40(3):241-254.

[iii] Lipton RB, et al. Neurology. 2020 Mar 31;94(13):e1365-e1377.

[iv] Villalón CM. Pharmacol Ther. 2009;124(3):309-323.

[v] Steiner TJ, et al. J Headache Pain. 2018;19(1):17.

[vi] Gustavsson A, et al. Eur Neuropsychopharmacol. 2011 Oct;21(10):718-79.

[vii] Lipton RB, et al. J Neurol. 2023; 270, 5692-5710.