Vyepti by H. Lundbeck A/S shows robust Phase IV efficacy in chronic migraine with medication-overuse headache patients

H. Lundbeck A/S (CPH: LUN) has reported statistically significant and rapid efficacy for its migraine-prevention drug Vyepti® (eptinezumab) in a challenging patient segment—those with chronic migraine compounded by medication-overuse headache (MOH). The full results from the Phase IV RESOLUTION trial were presented on June 21, 2025, during the European Academy of Neurology Annual Congress in Helsinki. This pivotal study demonstrated that eptinezumab not only reduced monthly migraine days (MMDs) and reliance on acute medication but also showed improvements in pain severity and broader quality-of-life outcomes when used in combination with standardized patient education.

The Danish biopharmaceutical company’s clinical update underscores the growing relevance of CGRP-targeting monoclonal antibodies in complex migraine cases, a field previously underserved by conventional therapies. Migraine remains the second-leading global cause of years lived with disability (YLD), with institutional interest steadily increasing in effective biologics that reduce both migraine frequency and functional burden.

How did eptinezumab perform in reducing migraine days and acute medication use during the RESOLUTION trial?

According to data shared at the neurology congress, patients in the eptinezumab arm of the trial experienced a mean reduction of 6.9 monthly migraine days during Weeks 1–4, compared to 3.7 days in the placebo group, with statistical significance reported at p<0.0001. The double-blind, placebo-controlled trial enrolled 608 patients across multiple European countries, all of whom were diagnosed with both chronic migraine and MOH.

Eptinezumab also led to a substantial reduction in the use of acute migraine medication. Patients receiving the drug reduced their reliance on acute treatment by 11.2 days per month, versus 7.8 days for those on placebo (measured across weeks 1–12). Baseline acute medication use was 20.1 days per month in both groups, indicating a meaningful shift in patient behavior and pharmacological dependence.

In terms of pain severity, improvements emerged as early as Week 2. The change in daily pain assessment score from baseline was -0.6 for eptinezumab, double the change observed in the placebo group (p<0.0001). These rapid effects position Vyepti as a potentially first-line solution in conjunction with educational interventions for MOH.

What makes the RESOLUTION trial significant in the context of difficult-to-treat migraine subtypes?

The RESOLUTION trial is the first randomized controlled study to evaluate the efficacy of an anti-CGRP therapy alongside structured patient education in patients suffering from both chronic migraine and MOH. MOH is a frequent complication among chronic migraine sufferers who overuse acute pain medications, which paradoxically worsen their headache frequency and lead to central sensitization.

In this study, both arms received a brief educational intervention (BEI)—a structured clinical conversation aimed at reducing over-reliance on acute medication. Patients were then randomized to receive either 100 mg of eptinezumab or placebo intravenously. The inclusion of BEI in both arms helps isolate the drug’s additive benefit and reflects a more real-world treatment scenario.

In terms of safety, 41.9% of eptinezumab-treated patients reported treatment-emergent adverse events compared to 36.9% in the placebo group, consistent with its prior safety profile in earlier trials such as PROMISE-1 and PROMISE-2.

How are institutional stakeholders responding to Lundbeck’s positioning of Vyepti for complex migraine cases?

Institutional sentiment remains cautiously optimistic around H. Lundbeck A/S’s ongoing development of CGRP inhibitors for both standard and complicated migraine profiles. Analysts view the RESOLUTION trial as a strategic expansion of Vyepti’s addressable market, particularly into a patient segment where standard treatments have underperformed.

While Vyepti already holds approvals in over 30 markets for adult migraine prevention—including the U.S. FDA’s nod in February 2020 and EU marketing authorization in January 2022—this new dataset adds a valuable use case backed by evidence from real-world complexity. Analysts expect broader adoption across neurologic clinics and specialty centers if pricing and insurance coverage are managed efficiently.

Given migraine’s high economic burden—costing EUR 18 billion annually in Europe alone—and the productivity losses associated with MOH, stakeholders see opportunities for Vyepti to deliver cost-offsets that may justify biologic-level pricing in targeted populations.

What do clinicians and trial leaders say about the early intervention strategy using anti-CGRP therapies?

Dr. Rigmor Højland Jensen, Director of the Danish Headache Center and principal investigator for the RESOLUTION trial, emphasized that early use of anti-CGRP therapy can break the cycle of escalating medication overuse. “The RESOLUTION trial demonstrates that adding an anti-CGRP treatment early, and alongside patient education, can deliver significant and rapid migraine prevention,” she stated during the congress.

This challenges the conventional sequencing of migraine therapies, which often reserves biologics for refractory patients after behavioral and pharmacologic interventions have failed. By shifting intervention earlier, Lundbeck positions Vyepti not just as a rescue solution, but as part of a proactive treatment framework.

What future opportunities could Vyepti unlock for Lundbeck in migraine and neurology markets?

Analysts expect the RESOLUTION trial to serve as a platform for expanded label applications in both the U.S. and Europe. Should regulators accept this dataset as proof of efficacy in MOH-complicated migraine, it could open pathways for increased prescribing, especially in high-volume neurology clinics dealing with chronic sufferers.

Future trials may focus on broader geographies, such as North America and Asia, to test cross-population efficacy. There’s also potential to examine other CGRP-associated disorders like cluster headaches or post-traumatic headache syndromes, leveraging eptinezumab’s pharmacologic mechanism and existing real-world safety data.

Lundbeck has signaled continued R&D investment into brain health and neuroscience, and Vyepti remains central to its strategy in non-psychiatric neurology. Institutional investors expect further clinical programs and potential post-marketing studies aimed at real-world effectiveness and health economics metrics.

How does Vyepti fit into the broader landscape of CGRP-targeting migraine treatments?

CGRP-targeting monoclonal antibodies have become a transformative class of biologics in migraine prevention, addressing a pathway that underlies both pain transmission and vascular inflammation. Vyepti, approved in 2020, competes with other CGRP inhibitors like fremanezumab and galcanezumab but distinguishes itself via intravenous administration, allowing rapid onset—often within 24 hours of infusion.

This pharmacokinetic profile may offer advantages for patients with higher migraine burdens or those requiring fast stabilization. In PROMISE-1 and PROMISE-2 trials, patients receiving Vyepti achieved statistically significant reductions in MMDs within the first 12 weeks of treatment.

In terms of safety, most common adverse reactions include nasopharyngitis and hypersensitivity. However, postmarketing surveillance has also noted risks such as hypertension and Raynaud’s phenomenon, reinforcing the need for patient-specific risk-benefit evaluations.

What are the regulatory and clinical implications following the RESOLUTION trial results?

The RESOLUTION trial marks a turning point for migraine treatment pathways involving MOH patients. Regulatory submissions could follow in both the EU and U.S. to reflect this additional indication or usage guideline. If approved, it may redefine how physicians approach patients with chronic migraine and comorbid medication overuse, especially those resistant to oral preventives.

For H. Lundbeck A/S, this adds a scientific and commercial tailwind to its neuroscience-focused strategy. Investors will likely track subsequent trial launches, updated guidance on Vyepti revenue contribution, and pricing models in Europe, where budget impact assessments are increasingly shaping formulary decisions.

In the immediate term, clinician awareness campaigns and payer dialogues will determine whether the trial’s promise translates into prescription volume, particularly in systems with strong primary care gatekeeping.