December 20, 2021 (Shanghai, China) – Jiangsu Hengrui Pharmaceuticals Co., Ltd. and its portfolio company Reistone Biopharma Co. Ltd. announced that the first patient had been dosed in a proof-of-concept (PoC) Phase 2 study to evaluate SHR1459 as monotherapy in treatment-naive patients with primary membranous nephropathy (PMN).

About SHR1459

SHR1459 is an orally available, small-molecule, covalent Bruton's tyrosine kinase inhibitor discovered by Hengrui. SHR1459 is highly selective with low off-target effects and high occupancy rate, without QT prolongation observed in its completed Phase 1 studies and ongoing Phase 2 studies. Due to its good safety profile, SHR1459 is currently being studied in both hematology and autoimmune indications.

Regarding the autoimmune indications, two Phase 2 studies are being conducted by Reistone for the treatment of neuromyelitis optica spectrum disorders (NMOSD) and primary membranous nephropathy (PMN), respectively. Preliminary data from the ongoing Phase 2 PoC study of NMOSD showed a promising profile of SHR1459, which will be presented in the upcoming J.P. Morgan 40th Annual Healthcare Conference. In addition, SHR1459 demonstrated strong efficacy signals in the animal model of Multiple Sclerosis (MS).

In 2018, the hematology malignancy indications of SHR1459 in most countries outside China were licensed to TG Therapeutics. SHR1459 demonstrated a compelling efficacy and safety profile in B-cell malignancies.¹ Currently, a global Phase III study is under planning for the treatment of hematology malignancy indications by TG Therapeutics.

About the Study

This study (NCT05136456) is a multicenter, randomized, double-blind, placebo-controlled, PoC Phase 2 study to evaluate SHR1459 as monotherapy in treatment-naive patients with PMN compared with placebo. This study is planned to enroll approximately 60 PMN patients from 10 sites in China.

The primary endpoint is the proportion of patients achieving clinical remission, including complete remission (CR) and partial remission (PR), at Week 24. The secondary endpoints include the proportion of patients with: 1) improvement in anti-phospholipase A2 receptor (PLA2R) autoantibody titer, and 2) changes in urinary protein, serum creatinine, and serum albumin relative to baseline within 52 weeks.

About Primary Membranous Nephropathy

Primary membranous nephropathy (PMN) is a kidney-specific, autoimmune glomerular disease that presents with increased protein in the urine associated with a pathognomonic pattern of injury in glomeruli, which accounts for about 75%-80% of all cases of membranous nephropathy (MN).² PMN is a leading cause of idiopathic nephrotic syndrome in nondiabetic adults worldwide, representing between 20% and 37% in most series and rising to as high as 40% in adults over 60.^(3,4,8) Most PMN is mediated by antibodies against the M-type PLA2R (70%-85%), thrombospondin type 1 domain-containing 7A (THSD7A) (3%–5%), or by other as yet unidentified mechanisms (10%).^(3-9)

About Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Hengrui is a leading global pharmaceutical company headquartered in China with a focus on research, development, manufacturing, and commercialization of innovative and high-quality healthcare products. Innovation is the core development strategy. Hengrui ranked the 24th among the top 1,000 global pharma companies in 2021.¹⁰ Hengrui has been on the Pharma Exec’s annual listing of the top global pharmaceutical companies for the third consecutive year, rising from the 47th in 2019 to the 38th in 2021.

1. https://www.tgtherapeutics.com/wp-content/uploads/2021/06/TG1701-101_ASCO2021_Poster_Cheah_FINAL.pdf

2. Clin J Am Soc Nephrol 12, 2017. doi: https://doi.org/10.2215/CJN.11761116

3. Cattran DC, Brenchley PE: Membranous nephropathy: Integrating basic science into improved clinical management. Kidney Int 91: 566–574, 2017

4. Salant DJ, Cattran DC: Membranous nephropathy. Chapter 20. In: Comprehensive Clinical Nephrology, 5th Ed., edited by Floege J, Johnson RJ, Feehally J, St. Louis, MI, Saunders, an imprint of Elsevier Inc., 2015, pp 239–251

5. De Vriese AS, Glassock RJ, Nath KA, Sethi S, Fervenza FC: A proposal for a serology-based approach to membranous nephropathy. J Am Soc Nephrol 28: 421–430, 2016

6. Francis JM, Beck LH Jr., Salant DJ: Membranous nephropathy: A journey from bench to bedside. Am J Kidney Dis 68: 138–147, 2016

7. Debiec H, Ronco P: Immune response against autoantigen PLA2R is not gambling: Implications for pathophysiology, prognosis and therapy. J Am Soc Nephrol 27: 1275–1277, 2016

8. Ronco P, Debiec H: Pathophysiological advances in membranous nephropathy: Time for a shift in patient’s care. Lancet 385: 1983– 1992, 2015

9. Sinico RA, Mezzina N, Trezzi B, Ghiggeri GM, Radice A: Immunology of membranous nephropathy: From animal models to humans. Clin Exp Immunol 183: 157–165, 2016

10. https://torreya.com/publications/pharma-1000-report-torreya-2021-11-08.pdf.  

BD Contact

Email: bd@hengrui.com

Phone: +86-21-61053532