Lundbeck is to showcase innovative trial design at ENDO 2024 of the first in human trial of Lu AG13909 for congenital adrenal hyperplasia (CAH), a rare debilitating disease with excess morbidity and mortality. H. Lundbeck A/S (Lundbeck) will present the novel design of the first in Human trial of Lu AG13909, a potential first-in-class treatment for CAH, at ENDO in Boston. The presentation will take place on 3 June 2024, at 12:00 (noon) EDT.

Lu AG13909 is a first-in-class monoclonal antibody, where early proof of mechanism has been established. Lu AG13909 aligns with Lundbeck's objective of investigating novel therapies for rare neurohormonal disorders. This addition reinforces Lundbeck's emphasis on the biology cluster focus within hormonal/neuropeptide signaling.

Lu AG13909 is a humanized anti-adrenocorticotropic hormone (ACTH) monoclonal antibody (mAb) that specifically recognizes ACTH with high affinity and blocks the ACTH binding to the melanocortin 2 receptor in the adrenal glands and thereby neutralizes the ACTH signaling. The ongoing trial is expected to be concluded by early 2025. The trial is a phase 1, open-label, multiple-ascending-dose trial with intra-participant dose escalation.

The trial enrolls men and women aged between =18 and =70 years with classic CAH. Each participant receives up to 6 doses of Lu AG13909 intra venously every 4-5 weeks at increasing dose levels. The trial consists of 2 parts: Part A is designed to escalate the dosage of Lu AG13909 in a small number of participants (N=3-6) to determine which Lu AG13909 dose levels are tolerable and pharmacologically relevant to be explored in a larger number of participants.

Part B is dedicated to exploring only those doses that have been deemed pharmacologically relevant from the findings in Part A. This exploration will be conducted in a larger group of participants (N=6-9), utilizing pharmacokinetic (PK) and pharmacodynamic (PD) data to guide the investigation. This structured approach ensures a thorough and systematic evaluation of Lu AG13909's potential therapeutic impact. The considerations incorporated into the trial design will ensure that most participants receive doses that are pharmacologically significant.

This approach aims to minimize the burden and risk associated with their participation in the trial. The primary safety and tolerability endpoints include adverse events and clinical safety tests. Pharmacokinetic endpoints include maximum observed exposure and area under the Lu AG13909 concentration-time curve in a dosing interval.

The pharmacodynamic endpoints are the relative reductions in morning 17-hydroxyprogesterone, androstenedione, and unbound ACTH, from baseline to the day after each Lu AG13909 dose. This trial is expected to inform Lundbeck about the potential of AG13909 to advance into mid-stage clinical development, as a new therapeutic approach for conditions marked by elevated ACTH levels, such as CAH.