Lu AG09222 / Lundbeck - LARVOL DELTA

Population pharmacokinetics and pharmacodynamics of Lu AG09222, an anti-PACAP monoclonal antibody in development for migraine prevention (EHF-EHC 2025) - "Both popPK analysis and TMDD-based model simulations of Lu AG09222 demonstrated prolonged, high-level PACAP inhibition after IV and SC administration. These results support the potential of Lu AG09222 for sustained PACAP binding and inhibition in migraine prevention."

Clinical • PK/PD data • CNS Disorders • Migraine • Pain • ADCYAP1

Pharmacokinetics and safety of Lu AG09222, an anti-PACAP monoclonal antibody in development for migraine prevention (EHF-EHC 2025) - "Data were included from a (1) first-in-human single ascending dose trial in healthy participants, including a cohort with co-administered sumatriptan (Lu AG09222 n=68; placebo n=28); (2) single-dose trial in healthy Caucasian, Chinese, and Japanese participants (Lu AG09222 n=40; placebo n=12); and (3) multiple-dose trial in participants with symptomatic allergic rhinitis (Lu AG09222 n=20; placebo n=10). Lu AG09222 exhibited a consistent PK profile across dosing regimens, route of administration and race/ethnicity. Across these trials, no safety concerns were identified, and Lu AG09222 was generally well-tolerated."

Clinical • PK/PD data • Allergic Rhinitis • CNS Disorders • Immunology • Inflammation • Migraine • Pain • ADCYAP1

Participant perspectives on clinical trial experience: Insights from exit interviews from the anti-PACAP antibody Phase 2 HOPE trial for migraine prevention (EHF-EHC 2025) - P2 | "To explore perspectives and experiences of clinical trial participation among people living with migraine who participated in the Phase 2 HOPE trial (NCT05133323) investigating the efficacy and safety of Lu AG09222, an anti-pituitary adenylate cyclase-activating polypeptide (anti-PACAP) monoclonal antibody in development for migraine prevention...Incorporating qualitative exit interviews into the trial design enabled people living with migraine to provide their perspective on clinical trial participation. Insights from these interviews can inform a participant-centric approach to future trial designs."

Clinical • Interview • P2 data • CNS Disorders • Migraine • Pain • ADCYAP1

PROCEED: A Dose-finding Trial With Lu-AG09222 in Adults With Migraine Who Have Not Been Helped by Prior Preventive Treatments (clinicaltrials.gov) - P2 | N=874 | Active, not recruiting | Sponsor: H. Lundbeck A/S | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Migraine • Pain

A Trial Investigating Lu AG09222 With Ubrogepant in Participants With Migraine (clinicaltrials.gov) - P1 | N=43 | Completed | Sponsor: H. Lundbeck A/S | Recruiting ➔ Completed

Trial completion • CNS Disorders • Migraine • Pain

Patient perspectives of migraine symptomology: Insights from exit interviews from the anti-PACAP antibody phase 2 HOPE trial for migraine prevention (IHC 2025) - P2 | "Methods The phase 2 HOPE trial investigated the efficacy and safety of Lu AG09222, an investigational humanized anti-pituitary adenylate cyclase-activating polypeptide (anti-PACAP) monoclonal antibody for migraine prevention...Conclusion In embedded trial interviews conducted during the HOPE trial, participants were more likely to spontaneously report common migraine symptoms whereas cognitive symptoms were reported more often in response to probes. These findings highlight the importance of comprehensive symptom assessment to better understand the burden of migraine."

Clinical • Interview • P2 data • CNS Disorders • Migraine • ADCYAP1

Lundbeck demonstrates leadership...with six presentations at the 2025 International Headache Congress (IHC), including three oral presentations on eptinezumab (Vypeti) and Lu AG09222 (anti-PACAP mAb) (PRNewswire)

Clinical data • Migraine

Is PACAP the next big thing in migraine therapy? (PubMed, Cephalalgia) - No abstract available

Journal • CNS Disorders • Migraine • Pain • ADCYAP1

Patient perspectives of migraine symptomology: Insights from exit interviews from the anti-PACAP antibody phase 2 HOPE trial for migraine prevention (AHS 2025) - P2 | " The phase 2 HOPE trial investigated the efficacy and safety of intravenous Lu AG09222, an investigational humanized anti-pituitary adenylate cyclase-activating polypeptide monoclonal antibody for migraine prevention... In embedded trial interviews performed during the HOPE trial, participants were more likely to spontaneously report common migraine symptoms whereas cognitive symptoms were reported more often in response to probes. Although methodological limitations introduced potential selection/response bias in this sample, these findings highlight the importance of comprehensive symptom assessment to better understand the burden of migraine. Future work to determine the generalizability to the broader population with migraine may pave the way for constructing more patient-centered evidence-generation programs."

Clinical • Interview • P2 data • CNS Disorders • Migraine • Pain • ADCYAP1

PACAP and migraine. (PubMed, Brain) - "In a small, short, proof of concept study a monoclonal antibody directed against PACAP (Lu AG09222) showed efficacy in the reduction of monthly migraine days compared to placebo, but failed for the endpoint 50%-reduction in migraine days. The ongoing PROCEED-study is a double-blind, placebo-controlled, dose-finding study investigating four different doses of Lu AG09222 vs placebo for migraine prevention is expected to complete in the second half of 2025."

Journal • CNS Disorders • Migraine • Pain • ADCYAP1

PROCEED: A Dose-finding Trial With Lu-AG09222 in Adults With Migraine Who Have Not Been Helped by Prior Preventive Treatments (clinicaltrials.gov) - P2 | N=898 | Recruiting | Sponsor: H. Lundbeck A/S | N=498 ➔ 898 | Trial completion date: Sep 2025 ➔ Apr 2026 | Trial primary completion date: Jul 2025 ➔ Feb 2026

Enrollment change • Trial completion date • Trial primary completion date • CNS Disorders • Migraine • Pain

Following a planned interim analysis in the PROCEED trial Lundbeck expands the dose finding to intravenous administration of Lu AG09222 in migraine prevention (PharmiWeb) - "Lundbeck A/S (Lundbeck) is announcing reaching 75% recruitment target in the SC dose-finding part (Part A) in the phase IIb PROCEED trial, that explores dose and route of administration of the anti-PACAP mAb Lu AG09222....The PROCEED trial is expected to be completed in the first half of 2026 with planned pivotal phase III initiation in second half of 2026."

Enrollment status • New P3 trial • Trial completion date • Migraine

A Trial Investigating Lu AG09222 With Ubrogepant in Participants With Migraine (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: H. Lundbeck A/S | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Migraine • Pain

A Monoclonal Antibody to PACAP for Migraine Prevention. (PubMed, N Engl J Med) - P2 | "In a phase 2 trial, a single intravenous infusion of 750 mg of Lu AG09222 showed superiority over placebo in reducing migraine frequency over the subsequent 4 weeks. (Funded by H. Lundbeck; HOPE ClinicalTrials.gov number, NCT05133323.)."

Clinical • Journal • CNS Disorders • Fatigue • Infectious Disease • Migraine • Novel Coronavirus Disease • Pain • Respiratory Diseases • ADCYAP1

A Trial Investigating Lu AG09222 With Ubrogepant in Participants With Migraine (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: H. Lundbeck A/S

New P1 trial • CNS Disorders • Migraine • Pain

PROCEED: A Dose-finding Trial With Lu-AG09222 in Adults With Migraine Who Have Not Been Helped by Prior Preventive Treatments (clinicaltrials.gov) - P2 | N=498 | Recruiting | Sponsor: H. Lundbeck A/S | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Migraine • Pain

PROCEED: A Dose-finding Trial With Lu-AG09222 in Adults With Migraine Who Have Not Been Helped by Prior Preventive Treatments (clinicaltrials.gov) - P2 | N=498 | Not yet recruiting | Sponsor: H. Lundbeck A/S

New P2 trial • CNS Disorders • Migraine • Pain

Lundbeck’s progresses first-in-class therapy for migraine prevention (The Pharma Letter) - "Danish CNS specialist Lundbeck...today announced the advancement of the clinical development of for migraine prevention with the initiation of PROCEED, a randomized, double-blind, Phase IIb, dose-finding trial to assess efficacy and safety of multiple subcutaneously administered doses. The PROCEED trial builds on the positive results of the HOPE Phase IIa proof-of-concept trial demonstrating efficacy of intravenously administered Lu AG09222..."

New P3 trial • CNS Disorders • Migraine • Pain

Targeting the PACAP-38 pathway is an emerging therapeutic strategy for migraine prevention. (PubMed, Expert Opin Emerg Drugs) - "Lu AG09222 is a humanized monoclonal antibody targeting PACAP-38 that was effective in preventing physiological responses of PACAP38 and reducing monthly migraine days in individuals with migraine. Further studies are necessary to elucidate the clinical utility, long-term safety and cost-effectiveness of therapies targeting the PACAP pathway."

Journal • Review • CNS Disorders • Migraine • Pain • ADCYAP1

From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment. (PubMed, Cells) - "Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment, highlighting the significance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to or contraindicated to anti-CGRP therapies. By updating our knowledge of PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides, including VIP, as a novel treatment option for migraines."

Journal • Review • CNS Disorders • Migraine • Pain • ADCYAP1

Lundbeck presents clinical advances in migraine prevention with positive trial results at international headache congress (Cision) - P2 | N=237 | NCT05133323 | Sponsor: H. Lundbeck A/S | "H. Lundbeck A/S...announces new clinical data supporting the efficacy and tolerability of Lu AG09222 for the preventive treatment of migraine at the International Headache Congress (IHC) 2023 in Seoul, Korea. The presentations also include additional data from a proof-of-mechanism study showing that Lu AG09222 can halt PACAP38-triggered vasodilation and headaches....This trial met the primary endpoint; the difference from placebo in mean change in MMDs from baseline over weeks 1-4 was significant with the Lu AG09222 high dose (-2.0 [90%CI -3.5; -0.6]; one-sided p=0.01). The change from baseline in mean MMDs was -6.2 (standard error [SE] 0.66) with Lu AG09222 high dose and -4.2 (SE 0.67) with placebo. Lu AG09222 was generally well tolerated."

P2 data • CNS Disorders • Migraine • Pain

Correction: The effect of Lu AG09222 on PACAP38- and VIP-induced vasodilation, heart rate increase, and headache in healthy subjects: an interventional, randomized, double-blind, parallel-group, placebo-controlled study. (PubMed, J Headache Pain) - No abstract available

Clinical • Pain

The effect of Lu AG09222 on PACAP38- and VIP-induced vasodilation, heart rate increase, and headache in healthy subjects: an interventional, randomized, double-blind, parallel-group, placebo-controlled study. (PubMed, J Headache Pain) - P1 | "This proof-of-mechanism study demonstrated that Lu AG09222 inhibited PACAP38-induced cephalic vasodilation and increases in heart rate, and reduced concomitant headache. Lu AG09222 may be a potential therapy against migraine and other PACAP-mediated diseases."

Clinical • Journal • CNS Disorders • Giant Cell Arteritis • Migraine • Pain • ADCYAP1

Lundbeck announces positive phase II Proof of Concept results with Lu AG09222 in migraine prevention (Cision) - P2 | N=237 | HOPE (NCT05133323) | Sponsor: H. Lundbeck A/S | "H. Lundbeck A/S...announced positive results of the HOPE trial, a clinical proof of concept trial of Lu AG09222 as a potential treatment for the prevention of migraine (NCT05133323). The primary analysis concluded that there was a statistically significant difference (p=0.01) between Lu AG09222 and placebo in the mean change from baseline in the number of monthly migraine days over weeks 1 to 4....Lu AG09222 represents a potential new therapeutic option, targeting a pathway in migraine that is distinct from the recently available calcitonin gene-related peptide (CGRP) migraine treatment drug class."

P2 data • CNS Disorders • Migraine • Pain

A Study With Lu AG09222 in Adults With Migraine Who Have Not Been Helped by Prior Preventive Treatments (clinicaltrials.gov) - P2 | N=237 | Completed | Sponsor: H. Lundbeck A/S | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Migraine