FDA OKs Breakthrough Therapy Designation to Sonrotoclax for MCL

The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation (BTD) for sonrotoclax, a next-generation and potentially best-in-class investigational BCL2 inhibitor, for the treatment of adult patients with relapsed or refractory mantle cell lymphoma, according to a news release from BeOne Medicines Ltd.

“Breakthrough therapy designation is reserved for medicines with the potential to transform outcomes for patients with serious diseases. This recognition affirms the strength of the emerging data for sonrotoclax and its potential to become a new standard of care for people with relapsed or refractory mantle cell lymphoma,” Julie Lepin, senior vice president, chief regulatory affairs officer at BeOne, said in the release. “Additionally, by participating in Project Orbis, we may be able to accelerate access to sonrotoclax, potentially helping patients faster than previously imagined.”

The FDA granted sonrotoclax breakthrough therapy designation and included it in Project Orbis based on data from the phase 1/2 BGB-11417-201 study, which evaluated the drug in adults with relapsed or refractory mantle cell lymphoma after prior treatment with a Bruton’s tyrosine kinase inhibitor and anti-CD20 therapy.

Recently announced topline results showed that sonrotoclax may produce deep and lasting responses, positioning it to become the first BCL2 inhibitor approved in the U.S. for this patient population. BeOne plans to share the full results at an upcoming medical meeting, and the phase 3 CELESTIAL-RRMCL confirmatory study is ongoing.

The FDA grants breakthrough therapy designation to drugs showing early evidence of meaningful benefit for patients with serious diseases. Project Orbis, launched in 2019 by the FDA Oncology Center of Excellence, enables international collaboration to speed up access to promising cancer treatments.

This marks the first breakthrough designation for sonrotoclax and the second for BeOne’s hematology program. Sonrotoclax has also received fast track designation for mantle cell lymphoma and Waldenström macroglobulinemia, and orphan drug designation for adults with mantle cell lymphoma, Waldenström macroglobulinemia, multiple myeloma and acute myeloid leukemia — reinforcing its potential as an important step forward in BeOne’s efforts to advance care for B-cell cancers.

Fast track designation is a process designed to accelerate the development and review of drugs that treat serious conditions and address unmet medical needs. Orphan drug designation is granted to drugs intended to treat rare diseases that affect fewer than 200,000 people in the United States.

Study Details and Overview of Sonrotoclax’s Development

The global phase 1/2 BGB-11417-201 study is a multicenter, single-arm, open-label trial that enrolled 125 adults with relapsed or refractory mantle cell lymphoma who had previously received anti-CD20 therapy and a Bruton’s tyrosine kinase inhibitor. In part 1, 22 patients received daily doses of either 160 milligrams or 320 milligrams of sonrotoclax to evaluate its safety, tolerability and determine the recommended dose for part 2. In part 2, 103 patients received the selected daily dose of 320 mg, following a ramp-up period, to assess the drug’s efficacy. The primary endpoint is overall response rate, determined by an independent review committee, and secondary endpoints include complete response rate, duration of response and progression-free survival.

Sonrotoclax (BGB-11417) is a next-generation, investigational B-cell lymphoma 2 inhibitor designed to block one of the proteins that help cancer cells survive. It belongs to a class of drugs known as BH3 mimetics, which mimic natural signals that trigger cell death. Preclinical and early studies have shown sonrotoclax to be a highly potent and selective BCL2 inhibitor with a short half-life and no evidence of drug buildup. It has demonstrated encouraging clinical activity across multiple B-cell cancers, with nearly 2,000 patients enrolled in its global development program so far, as per the release.

Reference

1. “BeOne Medicines’ Sonrotoclax Granted Breakthrough Therapy Designation by U.S. FDA.” BeOne Medicine. Oct. 13th, 2025.

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