BeOne Medicines Ltd. (NASDAQ:ONC) announced that the US Food and Drug Administration (FDA) has accepted and granted Priority Review to its supplemental New Drug Application (sNDA) for BRUKINSA (zanubrutinib) in combination with rituximab for adults with previously untreated mantle cell lymphoma (MCL).
If approved, the combination would become the first chemotherapy-free regimen based on a Bruton tyrosine kinase (BTK) inhibitor authorised in the United States for first-line treatment of MCL.
The application is supported by results from the Phase 3 MANGROVE trial, which demonstrated a 43% reduction in the risk of disease progression or death compared with bendamustine plus rituximab, a standard chemoimmunotherapy regimen.
Phase 3 MANGROVE Trial Meets Primary Endpoint
The global, randomised Phase 3 MANGROVE study enrolled 510 patients across 157 active clinical sites worldwide.
The trial compared BRUKINSA plus rituximab against bendamustine plus rituximab in adults with previously untreated mantle cell lymphoma.
Treatment with BRUKINSA reduced the risk of disease progression or death by 43%, with a hazard ratio of 0.57 (95% confidence interval: 0.43–0.76; p<0.0001).
The study met its primary endpoint of progression-free survival, as assessed by an independent review committee.
BeOne reported that the combination’s safety profile was consistent with the established safety characteristics of both medicines, with no new safety signals identified.
Full MANGROVE results are scheduled for presentation during the Plenary Scientific Session at the 68th American Society of Hematology Annual Meeting on December 13, 2026.
BeOne Advances Chemotherapy-Free Treatment Strategy
Amit Agarwal, Chief Medical Officer, Hematology, at BeOne Medicines, said the regulatory development could provide an alternative to chemotherapy-based treatment for newly diagnosed patients.
“In newly diagnosed mantle cell lymphoma, chemoimmunotherapy remains a mainstay of frontline treatment despite the toxicity burden it carries,” Agarwal said.
“The FDA’s acceptance of our application brings us closer to a chemotherapy-free, BRUKINSA-based option that significantly reduces the risk of disease progression or death.”
The company is also pursuing regulatory expansion outside the United States.
A supplemental application for BRUKINSA in mantle cell lymphoma has been submitted to the European Medicines Agency, while China’s National Medical Products Administration has accepted a corresponding application.
Existing Approvals and Safety Profile
BRUKINSA is already approved in the United States for adults with relapsed or refractory mantle cell lymphoma, as well as several other B-cell malignancies, including chronic lymphocytic leukemia and Waldenström’s macroglobulinemia.
The drug is approved in more than 80 markets and has been used to treat over 310,000 patients worldwide, according to BeOne.
Its clinical development programme includes more than 8,000 patients across over 45 studies.
BRUKINSA carries risks of serious adverse reactions, including bleeding, infections, reduced blood cell counts, secondary malignancies, cardiac arrhythmias and liver toxicity.
Outlook for BeOne Medicines
The FDA’s Priority Review designation represents a regulatory milestone for BeOne’s efforts to expand BRUKINSA into first-line mantle cell lymphoma treatment.
The MANGROVE results provide evidence of improved progression-free survival compared with standard chemoimmunotherapy, although regulatory approval for the new indication remains pending.
Investors will be monitoring the FDA’s review process, the full clinical data presentation in December and the progress of applications in Europe and China.