NPSP-795 / Takeda - LARVOL DELTA

Characterization of quinazolinone calcilytic therapy for autosomal dominant hypocalcemia type 1 (ADH1). (PubMed, J Biol Chem) - "ATF936 and AXT914, as well as the amino alcohol calcilytics, NPS 2143 and NPSP795, were shown to bind at a common region with the CaSR transmembrane domain, which is also an ADH1 mutational hotspot...Oral administration of 10 mg/kg AXT914 to Nuf mice increased plasma PTH to 104±29 pmol/L compared to 23±4 pmol/L for vehicle-treated mice, p<0.05; and increased plasma albumin-adjusted calcium to 2.03±0.02 mmol/L compared to 1.84±0.02 mmol/L for vehicle-treated mice, p<0.001. These studies indicate that the quinazolinone calcilytics may have potential for treating ADH1."

Journal • Addiction (Opioid and Alcohol) • Endocrine Disorders • Genetic Disorders • Hypoparathyroidism • CASR

Calcilytic NPSP795 Increases Plasma Calcium and PTH in an Autosomal Dominant Hypocalcemia Type 1 Mouse Model. (PubMed, JBMR Plus) - "© 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research"

Journal • Preclinical

Treatment of Autosomal Dominant Hypocalcemia Type 1 with the Calcilytic NPSP795 (SHP635). (PubMed, J Bone Miner Res) - "NPSP795 increased plasma PTH levels in subjects with ADH1 in a dose-dependent manner, and thus, serves as proof-of-concept that calcilytics could be an effective treatment for ADH1. Albeit all mutations appear to be activating at the CaR, in vitro observations were not predictive of the in vivo phenotype, or the response to calcilytics, suggesting that other parameters impact the response to the drug."

Journal • Endocrine Disorders • Hypoparathyroidism • Renal Disease

Therapeutic effects of topical calcilytic in IgE/Th2 and alarmin-driven surrogates of human asthma (ERS 2019) - "Calcilytics show therapeutic benefit in both IgE/Th2 and alarmin-driven airways inflammation and hyperresponsiveness in animal asthma surrogates in vivo, suggesting that they will be effective against any stimulus potentially exacerbating human asthma by inducing an alarmin response in the airways."