Rezolute Presents RZ358 Clinical Data-Validated Model of the Pharmacokinetics and Glycemic Response in Congenital Hyperinsulinism at Pediatric Endocrine Society 2020 Annual Meeting

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[{"type":"text","content":"REDWOOD CITY, Calif., June 01, 2020 (GLOBE NEWSWIRE) -- Rezolute, Inc. (“Rezolute” or “the Company”) (OCTQB:RZLT) recently announced that it has validated pharmacokinetic (PK) and pharmacodynamic (PD) models of its lead clinical asset, RZ358. Phase 2a data in adult and pediatric patients with congenital hyperinsulinism (HI) were shown to be predicted by the constructed models, and demonstrated that RZ358 raises glucose into a normal target range in a disease- and exposure-dependent manner, consistent with its known allosteric mechanism of action. The data were accepted as an oral presentation at the Pediatric Endocrine Society (PES) 2020 Annual Meeting, held virtually.\n A Population PK (PopPK) and subsequent empirical exposure-response (ER) model were constructed using pooled PK, PD, and continuous glucose monitoring (CGM) data from all clinical studies conducted with RZ358. Pediatric simulations were performed using allometrically scaled PK parameters derived from adult data. The clinical data were well-described by the model, which was in turn used to characterize results from two completed Phase 2a open-label studies (X358602 and X358605) in adult (n=10) and pediatric (≥ 12 years; n=4) patients with congenital HI. In these studies, serial measurements of RZ358 and extended CGM were collected before and after intravenous administration of single (1, 3, 6, 9 mg/kg) and dual (3+6 mg/kg) doses of RZ358, respectively. PK/PD modeling was performed to describe RZ358 levels and exposure-response relationships in the CHI population. Patient data was consistent with PK/PD models. First, empirical glucose levels were well-described in the model as a function of RZ358 levels, which were in turn dose-proportional and well-described by the PK model. RZ358’s approximately 15-day half-life demonstrates the potential for once- to twice-monthly dosing. Observed pediatric PK fell within the ~90% prediction interval of simulated data, indicating that drug levels in children can be extrapolated from adults. Second, RZ358’s exposure-response profile was disease state-dependent: RZ358 resulted in a sustained ~50% increase in glucose into a target range of 70-180 mg/dL in patients with pronounced baseline hypoglycemia (median subset; n=7), whereas the subset of patients with relatively normal overall baseline blood glucose (median; n=7) remained wi...

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