FDA Grants Sonrotoclax Accelerated Approval as First BCL-2 Inhibitor for Relapsed/Refractory Mantle Cell Lymphoma

Overview

The U.S. Food and Drug Administration granted accelerated approval to sonrotoclax (Beqalzi) on May 13, 2026, clearing BeOne Medicines’ next-generation BCL-2 inhibitor for adults with relapsed or refractory mantle cell lymphoma (MCL) who have already received at least two lines of systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor, the Oncology Nursing Society reported. The decision makes Beqalzi the first BCL-2 inhibitor specifically approved for MCL in the United States, Pharmaceutical Technology noted — opening a direct challenge to AbbVie and Roche’s Venclexta (venetoclax), which until now has been used off-label in this setting, per MedCity News.

Trial and Efficacy

The approval rests on BGB-11417-201 (NCT05471843), a single-arm, multicenter Phase 1/2 trial in 103 adults with relapsed or refractory MCL who had previously received anti-CD20-based therapy and a BTK inhibitor, according to the ASCO Post. The overall response rate was 52% (95% CI 42, 62), with a median time to response of 1.9 months and a median duration of response of 15.8 months (95% CI 7.4, not estimable), after an estimated median follow-up of 11.9 months, the ASCO Post reported. The complete response rate was 16%, per Pharmaceutical Technology.

The FDA’s prescribing information includes warnings and precautions for tumor lysis syndrome (TLS), serious infections, and neutropenia, the Oncology Nursing Society reported. Across the 115-patient safety population, serious adverse reactions occurred in 37%, most frequently from pneumonia (10%), the ASCO Post reported. BeOne’s press release republished by BioSpace detailed additional safety figures: laboratory or clinical TLS occurred in 7% of patients who followed the recommended dose ramp-up, while serious infections occurred in 14% (Grade 3-4 in 17%, with 2.6% fatal) and Grade 3-4 neutropenia in 18% (Grade 4 in 6%).

Dosing and Mechanism

The recommended Beqalzi regimen begins with a four-week ramp-up phase to reduce TLS risk, followed by 320 mg taken orally once daily until disease progression or unacceptable toxicity, the Oncology Nursing Society reported. BeOne, headquartered in Basel, Switzerland, describes Beqalzi as a next-generation BCL-2 inhibitor designed for more selective and potent target inhibition than venetoclax, with a shorter half-life of four to six hours versus roughly 26 hours for Venclexta, MedCity News reported.

The regulatory designations stack reflected the unmet need: the FDA granted Beqalzi priority review, breakthrough therapy designation, and orphan drug designation, per the Oncology Nursing Society. BeOne’s press release on BioSpace added fast track designation to that list.

Confirmatory Trial

As is standard for accelerated approvals, BeOne must verify Beqalzi’s clinical benefit in a confirmatory study. That trial is CELESTIAL-RRMCL (NCT06742996), which is currently underway in 149 locations across 17 countries, Pharmaceutical Technology reported.

Reactions

Michael Wang, MD, of the MD Anderson Cancer Center, said the trial data “confirm its role as a foundational therapy for mantle cell lymphoma in the post-BTK inhibitor setting,” HealthTree reported.

What We Don’t Know

• Durability beyond the accelerated dataset. The pivotal trial reported a median follow-up of 11.9 months. Whether the median duration of response holds up — or extends — with longer follow-up will depend on CELESTIAL-RRMCL data over the coming years.
• Real-world competition with Venclexta. Although Beqalzi is the first BCL-2 inhibitor specifically labelled for MCL, venetoclax has been used off-label in the indication and is a familiar agent for hematologists. Leerink Partners’ analysts model approximately $100 million in Beqalzi MCL sales by 2030, per MedCity News — a modest figure relative to the broader BCL-2 market.
• Sequencing in practice. The label limits use to patients who have already failed at least two lines of therapy including a BTK inhibitor. How quickly community oncologists adopt Beqalzi at that line, versus continuing to reach for off-label venetoclax, will shape uptake in the first year.