Sonrotoclax Granted Accelerated Approval for R/R Mantle Cell Lymphoma

The FDA today granted accelerated approval for BeOne Medicines’ sonrotoclax, a next-generation BCL2 inhibitor, for adults with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 2 lines of systemic treatment, including a Bruton tyrosine kinase (BTK) inhibitor.¹

The therapy, to be sold as Beqalzi, is designed with both greater potency and selectivity, offering patients improved efficacy, tolerability, and ease of administration over venetoclax (Venclexta), which until now has occupied the BCL2 inhibitor market by itself. This is the only drug in the class specifically approved for MCL, BeOne Medicines noted in its statement.²

Efficacy for sonrotoclax was evaluated in BGB-11417-201 (NCT05471843), a single-arm, multicenter trial involving 103 adults with relapsed or refractory MCL who previously received anti-CD20–based therapy and a BTK inhibitor. According to today’s statement from the FDA, the overall response rate (ORR) and duration of response (DOR) were assessed by an independent review committee using Lugano criteria. ORR was 52%, with a median time to response of 1.9 months, and the median DOR was 15.8 months, following an estimated median follow-up of 11.9 months.¹

More Potency, Less Toxicity in Second-Generation Therapy

Michael Wang, MD, global principal investigator and the Puddin Clarke Endowed Professor, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, previously told The American Journal of Managed Care^® that sonrotoclax is 14 times more potent and 6 times more selective than venetoclax. The drug’s much shorter half-life means it does not accumulate in the body, limiting toxicity.³

“The data supporting the approval of sonrotoclax in the US confirm its role as a foundational therapy for mantle cell lymphoma in the post-BTK inhibitor setting, and demonstrate that it can deliver robust disease control when treatment choices are limited and outcomes are poor,” Wang said in BeOne’s release. “From a clinical perspective, this provides physicians with an important new option grounded in both efficacy and tolerability, fundamentally changing how we think about sequencing therapy in this disease.”²

The label will include warnings and precautions for tumor lysis syndrome (TLS), a known risk with BCL2 inhibitors, serious infections, and neutropenia. Of 115 patients with MCL evaluated for safety, serious adverse reactions occurred in 37%, most frequently from pneumonia (10%).¹

Dosing with sonrotoclax begins with a 4-week ramp-up phase to reduce the risk of TLS, followed by 320 mg taken orally once daily until disease progression or unacceptable toxicity. The review of sonrotoclax occurred under Project Orbis, an initiative of the FDA Oncology Center of Excellence.¹

Less Work for Community Physicians to Administer

BeOne officials have previously described how sonrotoclax was developed to address community physicians’ fears of TLS and the extensive laboratory requirements needed to administer venetoclax, with the hope that this therapy can be given at any practice to any patient.⁴

Amit Agarwal, MD, PhD, chief medical officer, Hematology, BeOne Medicines, said of the landmark approval, “BeOne is leading the advancement and enhancement of BCL2 inhibition to revolutionize how we treat patients living with B-cell malignancies. Today’s approval of Beqalzi represents critical progress for patients with mantle cell lymphoma and reinforces our strategy of building foundational medicines designed to raise the standard of care in B-cell malignancies.”²

MCL is a rare and often aggressive subtype of non-Hodgkin lymphoma. In the United States, approximately 3300 new cases of MCL are diagnosed each year. While many patients respond to initial therapy, relapse is common, and outcomes after progression can be poor, particularly after prior treatment with a BTK inhibitor.²

In addition, the FDA granted sonrotoclax fast track designation for Waldenström macroglobulinemia (WM), as well as orphan drug designation for the treatment of adult patients with WM, multiple myeloma, acute myeloid leukemia, and myelodysplastic syndrome.²

Sonrotoclax is currently being studied in combination with other therapeutics, including BeOne’s zanubrutinib (Brukinsa), as a potential treatment for CLL, with updated data expected to be presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. The combination is seen as a potential future treatment for MCL as well and is mentioned in the just-published ASCO Educational Book.⁵

References

1. FDA grants accelerated approval to sonrotoclax in relapsed or refractory mantle cell lymphoma. News release. FDA. May 13, 2026. Accessed May 13, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sonrotoclax-relapsed-or-refractory-mantle-cell-lymphoma
2. BeOne Medicines’ BEQALZI (sonrotoclax) approved by US FDA as first and only BCL2 inhibitor for R/R mantle cell lymphoma. News release. Business Wire. May 13, 2026. Accessed May 13, 2026. https://www.businesswire.com/news/home/20260513542161/en/BeOne-Medicines-BEQALZI-sonrotoclax-Approved-by-U.S.-FDA-as-First-and-Only-BCL2-Inhibitor-for-RR-Mantle-Cell-Lymphoma
3. Wang M. Sonrotoclax shows promising efficacy, improved tolerability in heavily pretreated MCL. AJMC^®. December 23, 2025. Accessed May 13, 2026. https://www.ajmc.com/view/sonrotoclax-shows-promising-efficacy-improved-tolerability-in-heavily-pretreated-mcl
4. Caffrey M. BeiGene’s Mehrdad Mobasher, MD, MPH, discusses CLL data, pipeline following ASH 2024. Am J Manag Care. 2025;31(Spec No 1):SP12.
5. Tix T, Kumar A, Eyre TA, Dreyling M. Modern management of mantle cell lymphoma. Am Soc Clin Oncol Educ Book. 2026;46(3):e517468. doi:10.1200/EDBK-26-517468