Eptinezumab-JJMR

To seek input from an advisory committee, the FDA has delayed its decision on Rexulti's post-traumatic stress disorder application from its original target action date of Feb. 8. The FDA is raising efficacy questions over Lundbeck and Otsuka’s proposed combination of their Rexulti with Viatris’ Zoloft as a treatment for post-traumatic stress disorder (PTSD).For an upcoming meeting of the FDA’s Psychopharmacologic Drugs Advisory Committee, the agency is asking an expert panel to weigh in on whether results from an exploratory phase 2 trial and a positive phase 3 study can overcome negative findings from a second phase 3 of the combination.“Discordant results” from the two phase 3 trials have FDA reviewers worried, especially since the agency said it was unable to identify an explanation for the differing outcomes despite “extensive exploratory analyses.”“This discordance complicates the interpretation of the overall efficacy evidence from these pivotal trials,” the FDA staff wrote in a document prepared for Friday’s meeting.As the FDA typically requires, Otsuka and Lundbeck conducted two well-controlled phase 3 studies to support the Rexulti-Zoloft combo in PTSD. The agency and the drugmakers agreed that the combo needed to “consistently outperform” Zoloft monotherapy, a standard first-line medication, to show convincing evidence of efficacy.One of the two studies, which tested Rexulti at 2 mg and 3 mg in separate cohorts, was “a clearly and convincingly negative study,” according to the FDA. The trial didn’t show statistical significance on its primary or secondary endpoints, the FDA noted, and neither dose was superior to Zoloft alone.The other study, which evaluated flexible dosing of Rexulti at either 2 mg or 3 mg in one group, was “robustly positive,” according to the briefing document. Given the conflicting results, Otsuka and Lundbeck submitted additional phase 2 results as supportive evidence and retrospectively selected three comparisons from the midstage, multi-arm study. The Rexulti-Zoloft combo showed statistical superiority against single-agent Zoloft using the drugmakers’ methods. But, as the FDA noted, the data cannot claim to demonstrate statistical significance under the study’s original design.In the two positive trials, the Rexulti-Zoloft regimen was associated with a statistically significant reduction in PTSD symptoms versus Zoloft alone, as measured by the change in the clinician-administered CAPS-5 score from baseline to Week 10. While the other phase 3 failed to meet its primary endpoint, reductions in PTSD symptom severity seen in the trial were consistent with the two positive studies, Otsuka and Lundbeck said when presenting the results last May.To seek input from the advisory committee, the FDA has delayed its decision on Rexulti from its original target action date of Feb. 8. In the wake of the delay, it's not clear when the agency aims to make its its decision on the filing. Meanwhile, Rexulti has delivered fast growth driven by increased U.S. demand in Alzheimer’s disease agitation. In the first quarter, Lundbeck recorded 1.5 billion Danish kroner ($233 million) of revenue from Rexulti, an increase of 28% at constant exchange rates. The atypical antipsychotic drug was cited alongside the CGRP migraine med Vyepti as Lundbeck’s main growth drivers during the period.

The full results of the phase IV RESOLUTION trial were presented at the European Academy of Neurology 2025 Annual Congress, where Vyepti® (eptinezumab) demonstrated statistically significant reductions compared to placebo in mean monthly migraine days (MMDs) within the first 4 weeks, in patients with chronic migraine and medication-overuse headache who also received standardized patient education Patients treated with eptinezumab reported rapid reductions in pain severity by Week 2, compared to placebo, alongside a significant reduction in the use of acute migraine medication Improvements were observed across patient-reported outcomes, including reductions in headache-related burden, migraine-related disability, work productivity loss, and activity impairment VALBY, Denmark, June 21, 2025 /PRNewswire/ -- H. Lundbeck A/S (Lundbeck) today announced the full results from the phase IV RESOLUTION trial. The trial was a randomized, placebo-controlled trial designed to evaluate the efficacy of eptinezumab versus placebo in patients with chronic migraine and associated medication-overuse headache who also received standardized patient education.1 The study was presented at the 11th Congress of the European Academy of Neurology taking place in Helsinki 21-24 June.2 Patients with chronic migraine and medication-overuse headache represent a specific subset of the migraine patient population who are severely impacted by the condition. These patients are trapped in a cycle of worsening migraine, whereby escalating use of acute medication diminishes effectiveness, and exacerbates disease burden.3,4 This patient population is often difficult to treat, as a result of the complexity of the condition.5 "Patient education is often employed as a therapeutic strategy for patients with chronic migraine and medication-overuse headache, while preventive anti-CGRP treatments are reserved for later stages," said Dr. Rigmor Højland Jensen, Associate Professor at University of Copenhagen, Director of the Danish Headache Center, and lead investigator on the RESOLUTION trial. "The RESOLUTION trial demonstrates for the first time, that adding an anti-CGRP treatment early, and alongside patient education about medication-overuse headache, can deliver significant and rapid migraine prevention. This is good news for patients severely impacted by migraine complicated by medication overuse." In the RESOLUTION trial (n = 608), eptinezumab met the both the primary and secondary endpoints, showing significantly greater monthly migraine day (MMD) reductions through Weeks 1 to 4 with eptinezumab, compared to placebo. Across an average of 21 days, the change from baseline in MMDs was -6.9 with eptinezumab treatment, compared to -3.7 days for placebo (p<0.0001).2 Patients also reduced their use of acute medication by more than half with eptinezumab and patient education, where the change from baseline in the number of days per month that patients relied on acute migraine treatment, was -11.2 with eptinezumab, versus -7.8 with placebo (across weeks 1 to 12, p<0.0001, baseline days with acute medication for eptinezumab was 20.1 and for placebo was 20.1).2 A reduction in daily pain severity was also observed with eptinezumab, as early as Week 2, where the change in baseline on the daily pain assessment score with eptinezumab was -0.6, versus -0.3 with placebo (p<0.0001).2 In addition to the notable reductions in MMDs, acute medication use, and pain severity, greater improvements were observed with eptinezumab vs placebo across multiple patient-reported outcomes measuring headache-related burden and health-related quality of life, migraine-related disability, work productivity and activity impairment.6 The proportion of participants with treatment-emergent adverse events was similar between arms (eptinezumab, 41.9%; placebo, 36.9%) indicating that eptinezumab was well tolerated, similar to previous trials in migraine prevention2 and to the current labelled safety information in the United States prescribing information and the EU Summary of Product Characteristics. "RESOLUTION further reinforces eptinezumab as an effective treatment option for patients severely impacted by migraine. We see robust benefits with eptinezumab, even on top of existing patient education. These results highlight Lundbeck's dedication to raising the bar in migraine treatment expectations, ensuring that even the most difficult-to-treat patients have access to effective solutions." said Johan Luthman, EVP, and Head of Research & Development at Lundbeck. 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.7 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.8 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 Europe9 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 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.10 The secondary headache of MOH is a common complication among individuals with primary headache disorders like chronic migraine. About the RESOLUTION trial The RESOLUTION trial was a phase IV, multi-national, randomized, double-blind, placebo-controlled trial.11 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. Key secondary endpoints included change from baseline in average daily pain assessment score (as accessed by 3-point pain intensity scale, mild, medium, severe), and change from baseline in acute medication use over 1-12 weeks. Other secondary and exploratory endpoints assessed monthly migraine days over weeks 1-12, MOH remission, transition from chronic to episodic migraine, reductions in headache-related burden, migraine-related disability, work productivity loss, activity impairment, and the safety and tolerability of eptinezumab in this patient population. The participants in the RESOLUTION trial were mainly from European countries. About Vyepti® (eptinezumab) Eptinezumab 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 eptinezumab was evaluated in two phase III clinical trials (PROMISE-1 in episodic migraine12 and PROMISE-2 in chronic migraine13), where eptinezumab 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 eptinezumab as early as Day 1 post-infusion. The safety of eptinezumab was evaluated in more than 2,000 adult patients with migraine who received at least one dose of eptinezumab. 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 eptinezumab 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, eptinezumab was granted marketing authorization by the European Commission (EC) for the prophylaxis of migraine in adults who have at least four migraine days per month. Today, eptinezumab s launched in more than 30 markets worldwide. INDICATION VYEPTI [eptinezumab-jjmr] is indicated for the preventive treatment of migraine in adults. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS VYEPTI [eptinezumab-jjmr] 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. Hypertension: Development of hypertension and worsening of pre-existing hypertension have been reported following the use of CGRP antagonists, including VYEPTI, in the post-marketing setting. Some of the patients who developed new-onset hypertension had risk factors for hypertension. There were cases requiring initiation of pharmacological treatment for hypertension, and in some cases hospitalization. Hypertension may occur at any time during treatment, but was most frequently reported within 7 days of therapy initiation. The CGRP antagonist was discontinued in many of the reported cases. Monitor patients treated with VYEPTI for new-onset hypertension or worsening of pre-existing hypertension, and consider whether discontinuation of VYEPTI is warranted if evaluation fails to establish an alternative etiology or blood pressure is inadequately controlled. Raynaud's Phenomenon: Development of Raynaud's phenomenon and recurrence or worsening of pre-existing Raynaud's phenomenon have been reported in the post-marketing setting following the use of CGRP antagonists. In reported cases with monoclonal antibody CGRP antagonists, symptom onset occurred a median of 71 days following dosing. Many of the cases reported serious outcomes, including hospitalizations and disability, generally related to debilitating pain. In most reported cases, discontinuation of the CGRP antagonist resulted in resolution of symptoms. VYEPTI should be discontinued if signs or symptoms of Raynaud's phenomenon develop, and patients should be evaluated by a healthcare provider if symptoms do not resolve. Patients with a history of Raynaud's phenomenon should be monitored for, and informed about the possibility of, worsening or recurrence of signs and symptoms. 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 . 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 approximately 5,700 employees in more than 50 countries and our products are available in more than 80 countries. For additional information, we encourage you to visit our corporate site and connect with us via LinkedIn. References: Kristoffersen ES, et al. J Neurol Neurosurg Psychiatry. 2015;86(5):505-12 Jensen RH, et al. ePresentation at EAN 2025 Katsarava Z, et al. Curr Pain Headache Rep 2012; 16: 86–92 Lipton RB, et al. J Neurol 2023; 270: 5692–5710 Da Silva AN, Lake AE 3rd. Headache. 2014;54:211–7 Tepper SJ, et al. ePresentation at EAN 2025 Villalón CM. Pharmacol Ther. 2009;124(3):309-323. Steiner TJ, et al. J Headache Pain. 2018;19(1):17. Gustavsson A, et al. Eur Neuropsychopharmacol. 2011;21(10):718-79. Lipton RB, et al. J Neurol. 2023; 270, 5692–5710. Jensen RH, et al. Front. Neurol. 2023; 14:1114654. Ashina M, et al. Cephalalgia. 2020;40(3):241-254. Lipton RB, et al. Neurology. 2020;94(13):e1365-e1377. CONTACT: H. Lundbeck A/S Ottiliavej 9, 2500 Valby, Denmark +45 3630 1311 [email protected] This information was brought to you by Cision The following files are available for download: WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED