On January 5, 2025, the official website of the National Medical Products Administration (NMPA) announced that sonrotoclax tablets, a B-cell lymphoma 2 (BCL-2) inhibitor independently developed by BeiGene, has been officially approved for marketing in China, with two indications obtained simultaneously: for the treatment of adult patients with previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and for the treatment of adult patients with mantle cell lymphoma (MCL) who have previously received anti-CD20 therapy and BTK inhibitor (BTKi) therapy.

This landmark approval makes sonrotoclax the third BCL-2 inhibitor worldwide and the second domestic one in China. It marks a major breakthrough in BeiGene's pipeline layout in the field of hematologic malignancies, providing a new-generation treatment option with the potential to be best-in-class for patients with relapsed and refractory B-cell malignancies.

PART.01
Next-Generation BCL-2 Inhibitor:
Mechanistic Optimization and Pharmacokinetic Breakthroughs

The BCL-2 protein family is a key regulator of cell apoptosis. In various B-cell malignancies, overexpression of BCL-2 protein can inhibit the programmed death of tumor cells, leading to their abnormal survival and drug resistance. Targeted inhibition of BCL-2 protein to restore the apoptotic pathway of tumor cells has become a core therapeutic strategy for hematologic malignancies such as CLL/SLL and MCL. As a next-generation selective BCL-2 inhibitor independently developed by BeiGene, sonrotoclax has achieved mechanistic optimization in multiple dimensions through its molecular design.

Compared with traditional BCL-2 inhibitors, sonrotoclax exhibits high potency and specificity. It can precisely bind to the BH3 domain of BCL-2 protein and block its interaction with pro-apoptotic proteins. Its most prominent pharmacokinetic characteristics are its short half-life and non-accumulating property, which hold significant clinical value in combination therapy and individualized dose adjustment. The short half-life allows for rapid drug clearance, enabling timely interruption or dose reduction in the event of adverse reactions and reducing the risk of severe toxicity. The non-accumulating property ensures the safety of long-term medication, avoiding potential organ damage caused by continuous drug accumulation in the body. These characteristics provide greater flexibility in clinical management and guarantee the safe use of the drug for high-risk or elderly patients.

PART.02
CLL/SLL Indication:
Unmet Medical Needs and New Hope

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease, accounting for approximately one-third of adult leukemias. The median overall survival (OS) of Chinese patients is shorter than that of Western patients, and they are more prone to disease progression and recurrence. For relapsed and refractory (R/R) patients who have received multiple lines of therapy such as BTK inhibitors, anti-CD20 monoclonal antibodies, or chemotherapy, subsequent treatment options are extremely limited, and there is an urgent clinical need for new regimens with high efficacy and low toxicity.

The approval of sonrotoclax for CLL/SLL is based on positive data from an open-label, multicenter Phase II registration study, BGB-11417-202 (NCT05479994). This study enrolled 100 heavily pretreated patients with R/R CLL/SLL. With a median follow-up of 14.4 months, results assessed by the Independent Review Committee (IRC) showed that the overall response rate (ORR) of sonrotoclax monotherapy reached 76%, among which the complete response (CR) or complete response with incomplete bone marrow recovery (CRi) rate was 19%. The median time to response (TTR) was 3.7 months, indicating the rapid onset of the drug.

Most crucially, the best rate of undetectable minimal residual disease (uMRD) in peripheral blood was as high as 49.0%, with a median time to achieve uMRD4 of 5.8 months. uMRD is a key indicator for evaluating deep remission in CLL treatment, predicting longer progression-free survival (PFS) and potential curative potential. In high-risk subgroups, including patients with unmutated IGHV, 17p deletion and/or TP53 mutation, and BTK mutation, the ORR and CR rates remained consistent, confirming its efficacy in patients with poor prognosis.

In terms of safety, sonrotoclax monotherapy was well-tolerated, with manageable toxicity and no clinical tumor lysis syndrome (TLS) reported. The overall risk-benefit ratio was excellent.

PART.03
MCL Indication:
Breaking Through the Dilemma of BTK Inhibitor Resistance

Mantle cell lymphoma (MCL) combines the rapid progression of aggressive lymphoma with the incurable nature of indolent lymphoma. Its incidence in China is approximately 1 in 620,000, with a median age of onset around 60 years old, and it is showing an upward trend alongside population aging. Almost all MCL patients will eventually progress to a relapsed and refractory (R/R) state. Particularly, patients who develop resistance after BTK inhibitor treatment have an extremely poor prognosis, with a median overall survival of less than one year and extremely limited treatment options.

The approval of sonrotoclax for MCL is based on the complete data from a global, multicenter, single-arm, open-label Phase I/II study, BGB-11417-201 (NCT05471843). This study enrolled 103 patients with R/R MCL who had previously received anti-CD20 therapy and BTK inhibitor treatment, all of whom were administered 320 mg of sonrotoclax. The results showed that the IRC-assessed overall response rate (ORR) was 52.4%, the complete response (CR) rate was 15.5%, the median time to response (TTR) was only 1.9 months, the median progression-free survival (PFS) reached 6.5 months, and the median duration of response (DOR) was 15.8 months, with the data still immature.

Notably, in the high-risk subgroup of patients with TP53 mutations, the ORR still reached 59.1%, indicating that it maintains potent activity against the most aggressive MCL subtypes. Based on the excellent data from this study, the U.S. Food and Drug Administration (FDA) granted it priority review designation in November 2025, intending to accelerate the approval of its indication for R/R MCL previously treated with BTK inhibitors. Sonrotoclax is expected to become the first BCL-2 inhibitor approved in this field in the United States.

PART.04
Global Competitive Landscape

To date, only three BCL-2 inhibitors have been approved for marketing worldwide. As the first-in-class BCL-2 inhibitor, AbbVie’s Venetoclax has obtained approvals for indications such as CLL/SLL and acute myeloid leukemia (AML) in the United States, China and other regions, with global sales reaching $2.583 billion in 2024, demonstrating strong market performance. Ascentage Pharma’s Lisaftoclax was approved in China in 2024, becoming the second globally and the first domestically developed BCL-2 inhibitor in China, currently mainly targeting patients with R/R CLL/SLL.

As a next-generation product, sonrotoclax’s differentiated advantages are reflected in multiple dimensions. First, its pharmacokinetic profile of short half-life and no accumulation offers greater flexibility in combination therapy and safety management. Second, in the field of MCL, sonrotoclax is the world’s first BCL-2 inhibitor to demonstrate clear efficacy in patients previously treated with BTK inhibitors, filling the treatment gap in this field. Third, its clinical development strategy is more systematic, covering not only monotherapy but also in-depth layout of combination regimens. The synergistic effects with drugs such as zanubrutinib and obinutuzumab have been demonstrated in early studies. Finally, leveraging its global R&D and commercialization network, BeiGene has launched global development programs involving over 2,200 patients, covering multiple tumor types including CLL, MCL, Waldenström’s macroglobulinemia (WM), multiple myeloma (MM), acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Its indication expansion potential far exceeds that of existing competitors.

Conclusion

The approval of sonrotoclax for two indications by BeiGene marks another major victory for Chinese innovative drugs in the field of hematologic malignancies. As the third BCL-2 inhibitor approved worldwide, it demonstrates the potential to become a best-in-class drug with its unique pharmacokinetic advantages, clinical value in filling the gap in MCL treatment, and in-depth layout of combination therapy strategies.

From deep remission with monotherapy to rapid clearance with combination therapy, from salvage therapy in later lines to challenging standard care in frontline settings, sonrotoclax is redefining the treatment paradigm for B-cell malignancies. This achievement will not only improve the survival prognosis of tens of thousands of CLL/SLL and MCL patients in China, but also enhance BeiGene’s core competitiveness in the global hematologic malignancy field, laying a solid foundation for its mission of "enabling patients worldwide to access high-quality drugs".

With the advancement of subsequent research and the deepening of global layout, sonrotoclax is expected to become another blockbuster innovative therapy contributed by BeiGene to global patients following zanubrutinib. Its clinical value and market prospects are worthy of continued attention and anticipation.