Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 1426 |
| INN | Sibeprenlimab |
| Status | Clinical |
| Drug code(s) | VIS649 |
| Brand name | None |
| mAb sequence source | mAb humanized |
| General Molecular Category | Naked monospecific |
| Format, general category | Full length Ab |
| Format details | None |
| Isotype (Fc) | IgG2 |
| Light chain isotype | kappa |
| Linker | None |
| Ave. DAR | None |
| Conjugated/fused moiety | None |
| Discovery method/technology | None |
| Target(s) | APRIL |
| Indications of clinical studies | IgA Nephropathy, Phase 1 in healthy subjects |
| Primary therapeutic area | Immune-mediated / inflammatory disorders |
| Most advanced stage of development (global) | Phase 3 |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | October 23, 2018 |
| Start of Phase 2 | July 20, 2020 |
| Start of Phase 3 | March 11, 2022 |
| Date BLA/NDA submitted to FDA | |
| Year of first approval (global) | None |
| Date of first US approval | |
| INN, US product name | None |
| US or EU approved indications | None |
| Company | Otsuka Pharmaceutical Development & Commercialization Inc. |
| Licensee/Partner | None |
| Comments about company or candidate | Oct 2024: Phase 3 VISIONARY study met its primary endpoint at prespecified interim analysis; sibeprenlimab demonstrated a statistically significant and clinically meaningful reduction in 24-hour uPCR after nine months of treatment; Otsuka plans to review interim results with the FDA to enable a potential regulatory submission for accelerated approval; study continues with final results expected in early 2026. Feb 2024: Otsuka Pharmaceutical Development & Commercialization, Inc. and Visterra, Inc., an Otsuka group company announce that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for the investigational drug sibeprenlimab for the treatment of immunoglobulin A nephropathy NCT05248646 Phase 3 study in IgA nephropathy started in March 2022. NCT05248659 Phase IgA nephropathy 2/3 started in April 2022. NCT04287985 Phase 2 in IgA nephropathy not yet recruiting when posted on Feb 27, 2020. NCT03719443 Phase 1 started in Oct 2018 recruiting as of last record update in Feb 2019. Otsuka Pharmaceutical Development & Commercialization, Inc. acquired Visterra |
| Full address of company | 2440 Research Blvd,, Rockville, MD 20850, United States, Phone, 301-424-9055 North America United States of America https://www.otsuka-us.com/who-we-are |
VIS649 is a monoclonal immunoglobulin G2 (IgG2) antibody targeting the B-cell growth factor APRIL. VIS649 was derived from parental mouse antibody 2419 following immunization with recombinant APRIL. Parental mAb 2419 was humanized with conversion to an IgG2κ with full retention of in vitro activity. VIS649 binds to human APRIL with low picomolar affinity and possesses subnanomolar blocking potency of APRIL binding and signaling through both its receptors, BCMA and TACI. VIS649 also exhibits potent inhibition of relevant APRIL-mediated B-cell activities including B cell proliferation, IgA production, and terminal B-cell survival. VIS649 targets a critical quaternary epitope within APRIL that overlaps with the high affinity (CRD2) receptor binding site and spanning the interface between two monomers to effectively neutralize oligomeric APRIL, the biologically relevant form of APRIL. VIS649 engages with Fc receptors reflecting the expected canonical binding characteristics of a human IgG2 isotype and binds only minimally to complement (C1q).
| Anticipated events | Possible BLA in 2025 |
| Factor(s) contributing to discontinuation | None |