Kidney Week

Abstract: PO2455

A First-in-Human Study of MAU868, a Novel Neutralizing Antibody Against BK Virus

Session Information

• Transplant Complications: Infection
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1902 Transplantation: Clinical

Authors

• Kovacs, Steven J., Novartis Institutes for BioMedical Research East Hanover, East Hanover, New Jersey, United States

Steven J. Kovacs,

• Abend, Johanna R., Novartis Institutes for BioMedical Research Emeryville, Emeryville, California, United States

Johanna R. Abend,

• Xu, Xiaoying, Novartis Institutes for BioMedical Research East Hanover, East Hanover, New Jersey, United States

Xiaoying Xu,

• Desai, Sachin, Novartis Institutes for BioMedical Research East Hanover, East Hanover, New Jersey, United States

Sachin Desai,

• Nguyen, Amanda, Novartis Institutes for BioMedical Research East Hanover, East Hanover, New Jersey, United States

Amanda Nguyen,

• Sterling, Laura M., Celerion Inc, Lincoln, Nebraska, United States

Laura M. Sterling,

• Hodges, Michael R., Amplyx Pharmaceuticals, Inc, San Diego, California, United States

Michael R. Hodges,

• Pertel, Peter, Novartis Institutes for BioMedical Research East Hanover, East Hanover, New Jersey, United States

Peter Pertel,

Background

Reactivation of BK virus (BKV) infection can cause significant kidney and bladder disease in immunocompromised patients. BKV nephropathy is a leading cause of allograft loss in kidney transplant recipients. There are currently no effective or BKV-specific therapies. MAU868 is a novel monoclonal human IgG1 that binds to the BKV major capsid protein (VP1) with potent in vitro neutralizing activity against the 4 major BKV genotypes (EC₅₀s ranging from 0.009 to 0.093 μg/ml).

Methods

MAU868 was administered i.v. (1, 3, 10, 30, and 100 mg/kg) or s.c. (3 mg/kg) to healthy adults in a randomized, placebo-controlled, blinded, single ascending dose design. Each i.v. cohort was 5 subjects (4 MAU868:1 placebo); the s.c. cohort was 8 subjects (6 MAU868:2 placebo). Subjects were observed for 24 h and followed for 106 d with routine safety monitoring and PK assessments. Ex vivo neutralizing activity of serum was measured before and 4 w after dosing. The range of doses included and exceeded the predicted clinically efficacious dose.

Results

33 subjects completed the study. Adverse events were mild and infrequent; those occurring in more than 1 subject included nasal congestion (3, 9.1%), oropharyngeal pain (3, 9.1%), and injection site hemorrhage (ecchymosis after s.c. injection; 2, 6.1%). There were no infusion reactions. No subject discontinued the study due to an adverse event or developed anti-drug antibodies. MAU868 PK was typical of a human IgG with a half-life of 23 to 30 d. AUC and Cmax were dose-proportional, ranging from 9880 to 1060000 µg*hr/mL and 24.7 to 2740 µg/mL (ie, no evidence of FcRn saturation). Day 29 plasma MAU868 concentrations, adjusted for extravascular distribution to estimate parenchymal exposure, were approximately 7- to 751-fold higher than the highest in vitro EC₅₀ (0.093 µg/mL). Maximum ex vivo neutralizing activity of serum was achieved for doses >10 mg/kg. Bioavailability after s.c. injection was 57.6%.

Conclusion

MAU868 was safe and well tolerated with PK typical for a human IgG. The ex vivo neutralizing activity suggests where the therapeutic range may be for the treatment or prevention of BKV disease. These results warrant further clinical investigation of MAU868 in patients with or at risk for BKV disease.

Funding

• Commercial Support – Novartis