2. Academic Validation
  3. ALD1613, a Novel Long-Acting Monoclonal Antibody to Control ACTH-Driven Pharmacology

ALD1613, a Novel Long-Acting Monoclonal Antibody to Control ACTH-Driven Pharmacology

  • Endocrinology. 2017 Jan 1;158(1):1-8. doi: 10.1210/en.2016-1455.
Andrew L Feldhaus 1,  Katie Anderson 1,  Benjamin Dutzar 1,  Ethan Ojala 1,  Patricia Dianne McNeill 1,  Pei Fan 1,  Jenny Mulligan 1,  Sam Marzolf 1,  Charlie Karasek 1,  Michelle Scalley-Kim 1,  Erica Stewart 1,  Jens Billgren 1,  Vanessa Rubin 1,  Kathleen Schneider 1,  David Jurchen 1,  Kathy Snow 1,  Shaun Barnett 1,  Barbara Bengtsson 1,  Brian Baker 1,  John A Latham 1,  Dan Allison 1,  Leon F Garcia-Martinez 1
Affiliations

Affiliation

  • 1 Alder BioPharmaceuticals, Inc., Bothell, Washington 98011.
PMID: 27906551 DOI: 10.1210/en.2016-1455
Abstract

Adrenocorticotropic hormone (ACTH) is the primary regulator of adrenal glucocorticoid production. Elevated levels of ACTH play a critical role in disease progression in several indications, including congenital adrenal hyperplasia and Cushing disease. We have generated a specific, high-affinity, neutralizing monoclonal antibody (ALD1613) to ACTH. In vitro, ALD1613 neutralizes ACTH-induced signaling via all 5 melanocortin receptors and inhibited ACTH-induced cyclic adenosine monophosphate accumulation in a mouse adrenal cell line (Y1). ALD1613 administration to wild-type rats significantly reduced plasma corticosterone levels in a dose-dependent manner. In rodent models with either chronic infusion of ACTH or acute restraint stress-induced ACTH, corticosterone levels were significantly reduced by ALD1613. Administration of ALD1613 to nonhuman primates on days 1 and 7 stably reduced plasma cortisol levels >50% for 57 days. ALD1613 demonstrates the potential of a monoclonal antibody to be an effective therapeutic for conditions with elevated ACTH levels.

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