bocunebart (Lu AG09222) / Lundbeck - LARVOL DELTA

Pituitary adenylate-cyclase activating polypeptide (PACAP)-targeting treatment as a potential migraine prophylactic therapy (PubMed, Ideggyogy Sz) - "Results from a Phase 2a randomized clinical trial using a human mAb against the PAC1 receptor (subcutaneous AMG 301) showed no difference between placebo and the active drug in reducing the number of monthly migraine days (MMD)...A recently published Phase 2 clinical trial investigating a human mAb targeting PACAP (a single 1500 mg intravenous dose of LY3451838) showed no difference in the reduction of MMDs in patients with episodic and chronic migraine. The results of the ongoing PROCEED study, which evaluates the efficacy of four different doses of Lu AG09222 in migraine prevention, are expected to be published soon. Based on the findings from early-phase observations with mAbs against PACAP and its receptor, further high-phase clinical studies are required."

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

Bocunebart (anti-PACAP monoclonal antibody Lu AG09222) in adults with migraine and prior preventive treatment failures: Phase 2 program outcomes (EAN 2026) - P2 | "Positive phase 2 findings support PACAP inhibition as a novel approach in migraine prevention. Overall, bocunebart reduced migraine burden in a severely impacted population with high unmet need. These findings support bocunebart's continued development as a potential first-in-class anti-PACAP mAb."

Clinical • Late-breaking abstract • P2 data • CNS Disorders • Migraine • 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 | Completed | Sponsor: H. Lundbeck A/S | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Migraine • Pain

Safety and tolerability of anti-PACAP monoclonal antibody Lu AG09222 when co-administered with a gepant in participants with migraine (AHS 2026) - "Lu AG09222 was well tolerated when co-administered with ubrogepant and did not alter ubrogepant pharmacokinetics. These data, together with similar results for co-administration with triptans presented previously, support the safety profile of Lu AG09222 for co administration with common acute migraine therapies."

Clinical • CNS Disorders • Migraine • Pain • ADCYAP1

Targeting PACAP in migraine prevention: Outcomes from the PROCEED phase 2b trial of bocunebart (Lu AG09222) (AHS 2026) - No abstract available

P2b data • CNS Disorders • Migraine • Pain • ADCYAP1

Safety and Tolerability of Anti-PACAP Monoclonal Antibody Lu AG09222 when Co-administered with a Gepant in Participants with Migraine (Yahoo Finance) - "The randomized, double-blind, placebo-controlled trial (NCT06578585) assessed the safety and tolerability of bocunebart (Lu AG09222) when co-administered with ubrogepant; Findings from the study demonstrate that the safety profile of bocunebart is supported with co-administration with gepants."

P1 data • Migraine

Targeting PACAP in migraine prevention: Outcomes from the PROCEED phase 2b trial of bocunebart (Lu AG09222) (Yahoo Finance) - "A phase 2b route of administration and dose-finding trial (NCT06323928) evaluated the efficacy, safety, and tolerability of bocunebart, including the difference between bocunebart (Lu AG09222) and placebo in mean change from baseline in monthly migraine days over Weeks 1-12; Findings validate targeting PACAP for migraine prevention and support the use of bocunebart as a potential preventive treatment option for people with severe migraine."

P2b data • Migraine

Lundbeck expects migraine drug candidate to enter phase 3 this year (MedWatch) - "Lundbeck’s phase 3 expectations for the candidate bocunebart represent a step toward achieving the CEO’s goal of having five to six candidates in mid-to-late-stage development by the end of 2026."

New P3 trial • Migraine • Pain

Consistent Pharmacokinetics Profile Found for Lu AG09222 Treatment in Migraine (DocWire) - "In patients receiving intravenous doses, the maximum serum concentration and area under curve increased in a dose-proportionate manner after a single dose. In those receiving subcutaneous doses, meanwhile, exposure increased proportionally across doses after multiple doses. No pharmacokinetics differences were identified based on patients’ sex or race/ethnicity. In the first trial, which included a cohort receiving co-administered sumatripan, this co-administration did not lead to pharmacokinetic interactions."

First-in-human • P1 data • Migraine

Safety and Tolerability of Anti-PACAP Monoclonal Antibody Lu AG09222 when Co-administered with a Gepant in Participants with Migraine (AAN 2026) - "Conclusions Lu AG09222 was well tolerated when co-administered with ubrogepant and did not alter ubrogepant pharmacokinetics. These data, together with similar results for co-administration with triptans presented previously, support the safety profile of Lu AG09222 for co-administration with common acute migraine therapies."

Clinical • CNS Disorders • Immunology • Migraine • Pain • ADCYAP1

Pharmacokinetics and Safety of Lu AG09222, an Anti-PACAP Monoclonal Antibody in Development for Migraine Prevention (AAN 2026) - "Design/Methods 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). Conclusions 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 • First-in-human • PK/PD data • Allergic Rhinitis • CNS Disorders • Immunology • Inflammation • Migraine • Pain • ADCYAP1

Lundbeck announces positive phase IIb top-line results with bocunebart (Lu AG09222; anti-PACAP mAb) in migraine prevention (Cision) - "The intravenous (IV) part of the phase IIb dose-finding PROCEED trial of bocunebart (Lu AG09222) met its primary endpoint in migraine prevention, demonstrating a statistically significant difference to placebo in the change from baseline in the number of monthly migraine days (MMDs) over weeks 1 to 12 in a population that experienced past treatment failures. The results demonstrate the potential of bocunebart in severe migraine. Additional analyses will be done to better understand the dose–response relationship across the investigated doses. Based on this positive outcome, Lundbeck will approach regulatory authorities to discuss the results and phase III design options."

P2b data • Migraine

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 antiPACAP monoclonal antibody in development for migraine prevention (EHF-EHC 2025) - " Data were included from a (1) first-inhuman 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 | "Objective: 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 cyclaseactivating 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