Endocrine Abstracts

JOINT1439

Introduction: Cushing’s disease (CD) is a rare disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Autonomous ACTH production induces hypercortisolemia, which is associated with increased morbidity and mortality. There is an unmet need for well-tolerated and effective treatments to treat hypercortisolemia. Lu AG13909 is a novel, high-affinity, anti-ACTH monoclonal antibody that inhibits ACTH-induced signaling. Here, we describe the BalanCeD trial design (NCT06471829), evaluating the efficacy, safety, tolerability, and pharmacokinetic/pharmacodynamic profile of Lu AG13909 in adults with CD.

Methods: BalanCeD is a phase 2, interventional, multi-site, open-label, multiple-ascending-dose trial with dose titration, which is being conducted in specialist sites across Europe, including Georgia. Eligible participants have ACTH-driven CD (defined by current Pituitary Society consensus guidelines) and 24-hour urinary free cortisol (UFC) >1.5 times the upper limit of normal. Participants may have had pituitary surgery >3 months prior to screening. Participants who had previously received cortisol-lowering medication must have completed a predefined washout period prior to dosing. The trial consists of 3 parts: Part A (22–30 weeks), Part B (32–52 weeks), and an Extension Period (52 weeks, with an additional 16-week Safety Follow-up Period). Part A includes an intravenous titration period to identify the dose that provides the optimal clinical response based on tolerability and pharmacodynamic assessments, a subcutaneous period, and a Safety Follow-up Period. Part B includes a subcutaneous titration period to identify the optimal dose for normalization of mean UFC, a maintenance period, and a Safety Follow-up Period. Part B will be initiated based on a Dosing Conference, evaluating the cumulative safety, tolerability, pharmacokinetics, and efficacy data from ≥3 participants in Part A; Part B may be initiated before the finalization of Part A. Only participants enrolled in Part B can opt into the Extension Period, which will evaluate long-term efficacy and safety. The primary efficacy endpoint is the response rate of UFC normalization at the end of the titration periods of Part A and Part B. Secondary endpoints include treatment-emergent adverse events and multiple pharmacokinetic endpoints.

Conclusions: The BalanCeD trial aims to evaluate the efficacy, safety, tolerability, and pharmacokinetics/pharmacodynamics of Lu AG13909 in adults with CD. Findings from this trial will reinforce the development of Lu AG13909 as a novel anti-ACTH treatment strategy for patients with CD.