Experience with a BKV-Specific, Neutralizing Monoclonal Antibody (MAU868) for Treatment of Severe BK Virus Nephropathy (BKVN) after Kidney Transplant (FDA EIND #139112)
1Cedars Sinai Medical Ctr, Los Angeles, CA, 2Novartis Institutes for BioMedical Research, East Hanover, NJ, 3Novartis Institutes for BioMedical Research, Emeryville, CA, 4Amplyx Pharmaceuticals, San Diego, CA
Meeting: 2020 American Transplant Congress
Abstract number: D-180
Keywords: Infection, Kidney transplantation, Polyma virus, Viral therapy
Session Information
Session Name: Poster Session D: Kidney: Polyoma
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: BK viral reactivation leading to nephropathy and allograft loss in kidney transplant recipients remains a significant challenge. No effective BKV-therapies are currently available. Management of infection involves reduction of immunosuppression (IS), which increases the risk of acute graft rejection. MAU868 is a novel, human monoclonal antibody directed against the major BK viral capsid protein, VP1. In vitro, MAU868 potently neutralizes the 4 major BKV genotypes, has a high barrier-to-resistance, and in healthy volunteers, exhibits a long half-life (range 23-30 days). Data are presented from the first patient with BKVAN treated with MAU868, under an expanded access program.
*Methods: A 31 YO female (60 kg, 157.5 cm) with ESRD due to SLE and on HD for 3 yrs, underwent A2→B pediatric en-bloc DDKT 8/2017. IS involved induction with thymoglobulin and maintenance with MMF, tacrolimus + prednisone. BK viremia developed 2M post-transplant (PT) and persisted despite IS reduction and switching (MMF to leflunomide) and treatment with IVIg.
*Results: By 8M PT, sCr increased from 0.9 to 2.4 mg/dL with BK viremia >104 DNA copies/mL and biopsy confirmed Grade 3 BKVN. Subsequently, the patient received three IV doses of MAU868 monthly during which time sCr and BK viremia were reduced from 2.4 to 1.6 mg/dl and by approximately 1.0 log10 copies/mL, respectively. A biopsy showed significant improvement in BKVN. No resistant-associated BKV variants were identified. A further 8 doses biweekly were received however no further reductions in BKV DNA occurred. MAU868 was considered safe and well-tolerated. The patient was subsequently re-treated for 3M with IVIg. Greater than 2 yrs PT, BK viremia remained <104 DNA copies/mL, sCr was 3.0 mg/dL and patient has not required dialysis.
*Conclusions: The medical need for a safe and effective anti-BKV therapy for prevention and/or treatment of clinically significant BK viral infection remains very high. Treatment with MAU868 was associated with viral load reductions and improvements in renal function. The efficacy of MAU868 in the prevention and/or treatment of BKV disease warrants further clinical investigation.
To cite this abstract in AMA style:
Jordan SC, Kovacs SJ, Abend JR, Ammerman N, Toyoda M, Nast CC, Huang E, Najjar R, Sethi S, Peng A, Lim K, Hodges MR, Vo A. Experience with a BKV-Specific, Neutralizing Monoclonal Antibody (MAU868) for Treatment of Severe BK Virus Nephropathy (BKVN) after Kidney Transplant (FDA EIND #139112) [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/experience-with-a-bkv-specific-neutralizing-monoclonal-antibody-mau868-for-treatment-of-severe-bk-virus-nephropathy-bkvn-after-kidney-transplant-fda-eind-139112/. Accessed November 22, 2024.« Back to 2020 American Transplant Congress