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AXT914
- Development stage
- Phase 1
- Lead developer
- Novartis
- Modality
- Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Allosteric Modulators → Classical Binding Small Molecules → Small Molecules
- Administration
- Oral
01
Overview
AXT914 is an orally active, small molecule calcilytic developed by Novartis. It acts as a negative allosteric modulator (antagonist) of the calcium-sensing receptor (CaSR) in the parathyroid gland, leading to rapid and transient release of parathyroid hormone (PTH)[1][2][7]. The drug was investigated for its potential as an osteoporosis therapy, aiming to mimic the bone-anabolic effects of subcutaneously administered PTH by triggering sharp and robust PTH release[1][2]. In early clinical studies involving healthy volunteers and postmenopausal women, AXT914 induced reproducible PTH-release profiles but did not result in expected changes in bone formation biomarkers. Instead, it caused dose-related increases in serum calcium levels[1]. Due to lack of efficacy on bone biomarkers and safety concerns related to hypercalcemia, development for osteoporosis was discontinued after phase 1 trials[7].
- Other names
- pd127836pd-127836pd 127836
02
Targets
CaSR (Extracellular calcium-sensing receptor)
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