BeOne Medicines’ Sonrotoclax Granted Breakthrough Therapy Designation by U.S. FDA, Set to Participate in Project Orbis
BeOne Medicines Ltd. (Nasdaq: ONC; HKEX: 06160; SSE: 688235), a global oncology-focused biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for sonrotoclax, its next-generation investigational BCL2 inhibitor. The designation applies to the treatment of adult patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), a rare and aggressive subtype of B-cell non-Hodgkin lymphoma.
In addition to the BTD, the FDA has accepted BeOne’s request for participation in Project Orbis, a collaborative initiative designed to accelerate global access to promising oncology therapies by enabling concurrent submission and review of regulatory applications among participating international health authorities.
“Breakthrough Therapy Designation is reserved for medicines that have the potential to transform patient outcomes for serious diseases,” said Julie Lepin, Senior Vice President and Chief Regulatory Affairs Officer at BeOne. “This recognition underscores the strength of the emerging clinical data for sonrotoclax and highlights its potential to become a new standard of care for patients with relapsed or refractory mantle cell lymphoma. By participating in Project Orbis, we are hopeful that we can accelerate global access, potentially bringing this therapy to patients faster than previously anticipated.”
Basis for FDA Designation
The FDA’s decision to grant sonrotoclax BTD and Project Orbis participation was informed by data from the BGB-11417-201 study, a Phase 1/2 clinical trial evaluating sonrotoclax in adult patients with R/R MCL who had previously received a Bruton’s tyrosine kinase inhibitor (BTKi) and anti-CD20 therapy.
Recent topline results from this study demonstrated deep and durable responses, highlighting the potential for sonrotoclax to become the first and only BCL2 inhibitor approved for R/R MCL in the United States. BeOne plans to present the full dataset at an upcoming medical congress, providing the scientific community with detailed efficacy and safety findings.
Building on these results, the Phase 3 confirmatory CELESTIAL-RRMCL study (BGB-11417-302; NCT06742996) is currently underway, further evaluating sonrotoclax’s safety and efficacy in this patient population.
Breakthrough Therapy Designation and Project Orbis
The Breakthrough Therapy Designation is intended to expedite the development and review of medicines that may offer substantial improvements over existing treatments for serious or life-threatening conditions. Sonrotoclax’s designation represents a major milestone as the first BTD for this compound and the second for BeOne’s hematology program.
Project Orbis, established by the FDA Oncology Center of Excellence in 2019, enables simultaneous submission and collaborative review of oncology therapies across multiple regulatory agencies. By participating in this program, BeOne aims to accelerate the availability of sonrotoclax to patients worldwide, aligning with the company’s mission to improve outcomes in B-cell malignancies.
Additional Regulatory Designations
In addition to BTD, sonrotoclax has received several other FDA designations that reinforce its potential as a transformative therapy in hematologic cancers:
- Fast Track Designation for R/R MCL and Waldenström macroglobulinemia (WM)
- Orphan Drug Designation for adult patients with MCL, WM, multiple myeloma (MM), and acute myeloid leukemia (AML)
These regulatory pathways are intended to expedite development, facilitate early dialogue with the FDA, and support accelerated access to patients with high unmet needs.
About Mantle Cell Lymphoma
Mantle cell lymphoma is a rare and aggressive subtype of B-cell non-Hodgkin lymphoma, accounting for roughly 5% of all NHL cases worldwide. It is estimated to affect approximately 28,000 people globally. MCL is often diagnosed at advanced stages, and nearly all patients eventually experience relapsed or refractory disease. Despite current therapies, the five-year survival rate remains around 50%, underscoring the urgent need for new treatment options.
The BGB-11417-201 Study
The BGB-11417-201 study (NCT05471843) is a global, multicenter, open-label, single-arm Phase 1/2 trial evaluating sonrotoclax in adult patients with R/R MCL after prior anti-CD20 therapy and BTKi treatment.
- Part 1 enrolled 22 patients to assess safety, tolerability, and identify the recommended dose (160 mg or 320 mg daily).
- Part 2 included 103 patients receiving the recommended 320 mg daily dose following a ramp-up period to assess efficacy.
Primary endpoint: Overall Response Rate (ORR) as assessed by an independent review committee (IRC).
Secondary endpoints: Complete response (CR) rate, duration of response (DOR), and progression-free survival (PFS).
About Sonrotoclax
Sonrotoclax (BGB-11417) is a next-generation, potentially best-in-class BCL2 inhibitor designed to target a key protein that helps cancer cells evade apoptosis. Classified as a BH3 mimetic, sonrotoclax mimics natural cell death signals to induce cancer cell death.
Preclinical and early clinical studies have demonstrated:
- High potency and specificity for BCL2
- Short half-life with no drug accumulation
- Promising activity across a range of B-cell malignancies
To date, nearly 2,000 patients have participated in BeOne’s global clinical development program for sonrotoclax, supporting its potential as a transformative therapy for patients with B-cell cancers.
