Abstract: PO2024
Subcutaneous VIS649, an APRIL-Neutralizing Antibody: Preliminary Pharmacokinetic (PK) and Pharmacodynamic (PD) Results of VIS649-102, a Phase 1, Single Ascending Dose Study in Healthy Volunteers
Session Information
- Clinical Pharmacology, Pharmacokinetics, and Drug Toxicity in Kidney Diseases
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Zhang, Xiaoyan, Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, New Jersey, United States
- Wang, Yanlin, Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, New Jersey, United States
- Yarbrough, Jill, Visterra, Inc., Waltham, Massachusetts, United States
- Schachter, Asher Daniel, Visterra, Inc., Waltham, Massachusetts, United States
- Sloan, Susan E., Visterra, Inc., Waltham, Massachusetts, United States
Background
Immunoglobulin A (IgA) nephropathy (IgAN) is in part driven by A proliferation-inducing ligand (APRIL). VIS649, a humanized immunoglobulin G (IgG2) monoclonal antibody that blocks APRIL, is currently in Phase 2 clinical development as a potential treatment for IgAN. The preliminary results of VIS649-102, a Phase 1 single ascending dose study of subcutaneously (SC) administered VIS649 in healthy volunteers is reported here.
Methods
VIS649 (200 mg/ mL liquid) was administered as a single dose via the SC route to four cohorts of 12 healthy adult volunteers each. Doses were 200 mg (1x1 mL SC), 400 mg (2x1 mL SC injections), 400 mg (1x2 mL SC injection), and 600 mg (1x2 mL and 1x 1 mL SC injection).
Results
SC-administered VIS649 was well tolerated, with no adverse events that led to study discontinuation, and no injection site reactions. Treatment Emergent AEs (TEAEs) were all mild and all resolved. There was no clinically relevant effect of treatment on laboratory tests, vital signs, or physical examinations. Preliminary PK results show bioavailability of approximately 75% compared to intravenous (IV)-administered VIS649 (Y. Suzuki et al, ERA-EDTA 2021). Single SC doses of either 400 mg or 600 mg suppress total IgA by up to approximately 50-55% from baseline values at 8 weeks post-dose. Single doses of 200 mg SC suppressed IgA by approximately 40% by 6 weeks post-dose. Overall, these preliminary results with SC VIS649 indicate a similar degree and trajectory of IgA suppression as that achieved by the IV formulation in healthy volunteers, in which the 6 mg/kg single IV dose suppressed IgA by approximately 50% from baseline values at 8 weeks post-dose (Figure 1).
Conclusion
Preliminary results of this Ph1 study of SC-administered VIS649 demonstrated acceptable safety, tolerability, amd bioavailability, and suppressed total IgA by approximately 50-55% from baseline, comparable to IV doses.
Figure 1. Total IgA Mean Percent Suppression From Baseline Following Single Dose VIS649 Administered Via SC or IV Route
Funding
- Commercial Support –