Lu AG13909 / Lundbeck - LARVOL DELTA

What is the need for adrenalectomy in patients with congenital adrenal hyperplasia in the era of CRF1/ACTH inhibitors? (PubMed, Front Endocrinol (Lausanne)) - "Now with the newly approved crinecerfont (a corticotropin-releasing factor type 1 receptor (CRF1) antagonist, approved by FDA in US December 2024), and the coming phase 3 study of atumelnant (a MC2R antagonist), the commenced phase 2 study of Lu AG13909 (an anti-ACTH monoclonal antibody) as well as the preclinical studies with OMass MC2R antagonist compounds, there may be new options to decrease the size of the adrenal tumors/hyperplasia. However, the cost of these new drugs may be very high so they may not become widely available, and adrenalectomy may prove to be more cost effective. This review will discuss the current use of adrenalectomy in patients with CAH and how the introduction of the new drugs may change it."

Journal • Review • Adrenal Cortex Carcinoma • Congenital Adrenal Hyperplasia • Endocrine Disorders • Genito-urinary Cancer • Oncology • Solid Tumor

A Novel Anti-ACTH Antibody Lu AG13909 in Clinical Development for Treatment of Classic Congenital Adrenal Hyperplasia: A Phase 1 Open-Label, Multiple-Ascending-Dose Study (ENDO 2025) - P1/2 | "Preliminary data (N=11) demonstrated clear pharmacodynamic effects following up to 6 intravenous infusions of Lu AG13909 at increasing doses, with consistent reductions in morning 17-OHP and A4 concentrations observed at all dose levels. No safety concerns were raised.Conclusions The preliminary results of this phase 1 study show that Lu AG13909 is well-tolerated and can reduce adrenal androgen production, reinforcing continued clinical development of Lu AG13909 as a novel anti-ACTH treatment strategy for classic CAH."

Clinical • P1 data • Congenital Adrenal Hyperplasia • Endocrine Disorders

A Phase 2, Open-Label Trial Evaluating the Efficacy and Safety of Anti-ACTH Antibody Lu AG13909 in Adults With Classic Congenital Adrenal Hyperplasia: Trial Design (ENDO 2025) - P1/2 | "Participants may enter an optional open-label extension, where they receive 12 IV administrations of Lu AG13909 at 4- to 5-week intervals, with daily GC dose optimization based on individual androgen concentrations.Outcomes The primary endpoint is biochemical response, defined as morning concentrations of A4 <upper limit of normal (pre-daily GC dosing) after 24 weeks of treatment in cohort C1. Other endpoints include relative reduction from baseline in morning concentrations of A4 and 17-OHP; relative reduction from baseline in GC daily dose; and the safety, tolerability, and PK profile of Lu AG13909.Conclusions This trial will evaluate the efficacy and safety of Lu AG13909 for lowering androgen concentrations, and GC dosing in adults with classic CAH, reinforcing the development of Lu AG13909 as a novel anti-ACTH treatment strategy."

Clinical • P2 data • Congenital Adrenal Hyperplasia • Endocrine Disorders

BalanCeD: A Trial of Lu AG13909 in Adult Participants With Cushing's Disease (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: H. Lundbeck A/S | Trial completion date: Mar 2028 ➔ Nov 2027

Trial completion date • Cushing’s Disease • Endocrine Disorders

Lundbeck receives orphan drug designation in the US and EU for Lu AG13909 for the treatment of patients with congenital adrenal hyperplasia (Yahoo Finance) - "Lundbeck today announces that orphan drug designation has been granted to Lu AG13909 by the US Food and Drug Administration (FDA) on 12 May 2025 and the European Medicines Agency (EMA) on 20 June 2025....Lundbeck is currently expanding an ongoing Phase I/II clinical open-label trial, evaluating the efficacy and safety of anti-ACTH antibody Lu AG13909 in adults with classic CAH. The trial will open for enrolment in North America and seven countries across Europe, with the first sites opening in late June 2025."

Orphan drug • Trial status • Congenital Adrenal Hyperplasia

A Trial of Lu AG13909 in Participants With Congenital Adrenal Hyperplasia (clinicaltrials.gov) - P1/2 | N=42 | Recruiting | Sponsor: H. Lundbeck A/S | Phase classification: P1 ➔ P1/2 | N=12 ➔ 42 | Trial completion date: Dec 2024 ➔ Feb 2028 | Trial primary completion date: Dec 2024 ➔ Sep 2026

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Congenital Adrenal Hyperplasia • Endocrine Disorders • CYP1A2 • CYP21A2

BalanCeD: A Trial of Lu AG13909 in Adult Participants With Cushing's Disease (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: H. Lundbeck A/S | Trial completion date: Dec 2027 ➔ Mar 2028

Trial completion date • Cushing’s Disease • Endocrine Disorders

New therapeutic steroid sparing options for Congenital Adrenal Hyperplasia (ESPE-ESE 2025) - "Crinecerfont, a corticotropin- releasing factor type 1 receptor (CRF1) antagonist was trialed in placebo-controlled studies for children and adults with 21OHD. Additional therapeutics targeting the HPA axis are in trials, particularly atumelnant, an orally administered MC2R (ACTH receptor) antagonist, and Lu AG13909, an antibody to ACTH. These treatments might allow simplified and less toxic glucocorticoid regimens for children and adults with 21OHD, to improve short- and long-term outcomes."

CNS Disorders • Congenital Adrenal Hyperplasia • Endocrine Disorders • Metabolic Disorders • Mood Disorders • Obesity • Osteoporosis • Pediatrics • Psychiatry

Symposium 27: Novel treatment options for adrenal insuffiency/CAH (ESPE-ESE 2025) - "Your key learning points for this session will be:Long-term health outcomes in adults with classic 21OHD are poor and mostly reflect high glucocorticoid exposure.Crinecerfont, a corticotropin-releasing factor type 1 receptor (CRF1) antagonist lowered androstenedione and allowed glucocorticoid dose reduction in children and adults with classic 21OHD.Atumelnant is an MC2R (ACTH receptor) antagonist in clinical trials for classic 21OHD.Lu AG13909 is an anti-ACTH antibody in clinical trials for classic 21OHD.• The discovery of 11-oxygenated androgens, particularly 11-ketotestosterone (11KT), challenges the long-standing view that only testosterone and DHT are potent androgens in human physiology. Patients with adrenal insufficiency require individualised replacement with corticosteroidsMany patients have normal quality of lifeConventional twic or trice daily hydrocortisone or cortisone acetate is adequate for the majorityExtended-release formulations may be..."

Castration-Resistant Prostate Cancer • Congenital Adrenal Hyperplasia • Endocrine Disorders • Genito-urinary Cancer • Nephrology • Oncology • Polycystic Ovary Syndrome • Prostate Cancer • Renal Disease • Solid Tumor

A Phase 2, Open-label, Multiple-Ascending-Dose Trial Evaluating Anti-ACTH Antibody Lu AG13909 in Adults With Cushing’s Disease: BalanCeD Trial Design (ESPE-ESE 2025) - P2 | "Findings from this trial will reinforce the development of Lu AG13909 as a novel anti-ACTH treatment strategy for patients with CD. 2"

Clinical • P2 data • Cushing’s Disease • Endocrine Disorders • Pituitary Gland Carcinoma • Rare Diseases

BalanCeD: A Trial of Lu AG13909 in Adult Participants With Cushing's Disease (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: H. Lundbeck A/S | Trial completion date: May 2026 ➔ Dec 2027 | Trial primary completion date: Feb 2026 ➔ Sep 2026

Trial completion date • Trial primary completion date • Cushing’s Disease • Endocrine Disorders

BalanCeD: A Trial of Lu AG13909 in Adult Participants With Cushing's Disease (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: H. Lundbeck A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Cushing’s Disease • Endocrine Disorders

BalanCeD: A Trial of Lu AG13909 in Adult Participants With Cushing's Disease (clinicaltrials.gov) - P2 | N=18 | Not yet recruiting | Sponsor: H. Lundbeck A/S

New P2 trial • Cushing’s Disease • Endocrine Disorders

Safety And Pharmacokinetics Of Anti-ACTH Antibody Lu AG13909 In Patients With Classic Congenital Adrenal Hyperplasia: Phase 1 Open-label, Multiple-ascending-dose Trial Protocol (ENDO 2024) - "The aim of the trial is to gather safety, PK, and PD data while minimizing participant risk and burden. Data from this trial will reinforce the development of Lu AG13909 as a novel treatment strategy in conditions characterized by increased levels of ACTH, such as classic CAH and Cushing disease."

Clinical • Late-breaking abstract • P1 data • PK/PD data • Congenital Adrenal Hyperplasia • Cushing’s Disease • Endocrine Disorders