Otsuka Pharmaceutical Co., Ltd. (Otsuka); Otsuka Pharmaceutical Developmment & Commercialization, Inc., (OPDC); 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 nephropathy (IgAN; Berger's disease).

Sibeprenlimab is a humanized monoclonal antibody that blocks the action of B cell growth factor, cytokine APRIL(an acronym for a proliferation-inducing ligand), which plays a key role in the development and progression of IgAN.^1,4,5 The Breakthrough Therapy designation is based on the favorable results of the Phase 2 ENVISION clinical trial evaluating sibeprenlimab in IgAN patients. The trial results have also been published in The New England Journal of Medicine.¹

Breakthrough Therapy designation is granted by the FDA for a drug intended to treat a serious condition when preliminary clinical evidence indicates that the candidate may demonstrate substantial improvement over existing therapies on at least one clinically significant endpoint.

Otsuka Pharmaceutical and Visterra Inc. are committed to advancing the ongoing Phase 3 trial for sibeprenlimab to address the unmet needs of patients with IgAN.

About Immunoglobulin A Nephropathy

Immunoglobulin A nephropathy (IgAN; Berger's disease) is the most common form of primary glomerulonephritis worldwide and is the most common cause of kidney failure in young adults.^2,3 The disease is associated with a reduction in life expectancy of 10 years,³ with at least 30 percent of affected patients progressing to kidney failure within 20 to 30 years, despite optimized standard of care therapy.^6,7

Current standard of care management is based on renin-angiotensin aldosterone system (RAAS) blockers and adequate blood pressure control, but the risk of kidney failure remains high.⁸

About Sibeprenlimab

Sibeprenlimab (formerly VIS649) is an investigational humanized IgG2 monoclonal antibody that reduces the production of Gd-IgA1 by binding to a specific signaling molecule called APRIL (short for "a proliferation-inducing ligand"), which has been demonstrated to be a driver of IgA and Gd-IgA1 production. By binding and neutralizing APRIL, sibeprenlimab may reduce the amount of IgA and Gd-IgA1. Lower levels of Gd-IgA1 may then result in reduced auto-antibody production, which in turn may result in fewer immune complexes, decreased immune complex deposits in kidney, and reduced kidney inflammation. By reducing the production of Gd-IgA1, sibeprenlimab is believed to prevent further kidney damage and the progression to end stage kidney disease.^1,4,5

1. *1Mathur M, Barrat J, Chacko B, et al. A Phase 2 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy Patients. NEJM. 2023 https://www.nejm.org/doi/full/10.1056/NEJMoa2305635
2. *2Floege J, Amann K. Primary glomerulonephritides. Lancet. 2016;387(10032):2036-2048.
3. *3Hastings MC, Bursac Z, Julian BA, et al. Life Expectancy for Patients From the Southeastern United States With IgA Nephropathy. Kidney Int Rep. 2017;3(1):99-104.
4. *4Mathur M, Barratt J, Suzuki Y, et al. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VIS649 (Sibeprenlimab), an APRIL-Neutralizing IgG2 Monoclonal Antibody, in Healthy Volunteers. Kidney Int Rep. 2022;7(5):993-1003.
5. *5Chang S, Li XK. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy. Front Med (Lausanne). 2020;7:92.
6. *6Lai KN, Tang SC, Schena FP, et al. IgA nephropathy. Nat Rev Dis Primers. 2016;2:16001.
7. *7Gleeson PJ, O'Shaughnessy MM, Barratt J. IgA nephropathy in adults - Treatment Standard [published online ahead of print, 2023 Jul 7].
8. *8Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 Oct;100(4S):S1-S276. doi: 10.1016/j.kint.2021.05.021. PMID: 34556256.