BeiGene Announces the Approval of BRUKINSA™ (Zanubrutinib) in China for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma and Relapsed/Refractory Mantle Cell Lymphoma
BRUKINSA received accelerated approval from the
“The concurrent approvals of BRUKINSA in R/R CLL/SLL and R/R MCL are a tribute to the collective expertise and hard work of the
“Following in the footsteps of tislelizumab, BRUKINSA is the second
The NMPA Approval in R/R CLL/SLL
The NMPA approval of BRUKINSA in patients with R/R CLL/SLL is based on results from a single-arm pivotal Phase 2 trial conducted in 91 patients (82 with R/R CLL; nine with R/R SLL) in
The most common adverse reactions reported in the label in
“The approval of BRUKINSA will provide an important treatment option for Chinese patients with relapsed/refractory CLL/SLL. In addition to BRUKINSA’s significant anti-tumor activity evidenced by an ORR of more than 60%, the drug demonstrated a favorable safety and tolerability profile,” commented
The NMPA Approval in R/R MCL
The NMPA approval of BRUKINSA in patients with R/R MCL is based on results from a single-arm pivotal Phase 2 trial conducted in 86 patients in
The most common adverse reactions (≥10%) reported in the label in
“BRUKINSA has shown promise in hematologic malignancies including in patients with relapsed/refractory MCL. With robust results including a 68.6% CR rate in the MCL trial, we are optimistic and excited about the clinical benefits BRUKINSA can bring to these patients,” said
The recommended dose of BRUKINSA in Chinese Package Insert is 160 mg twice daily taken orally with or without food. The dose may be adjusted for adverse reactions, and reduced for patients with severe hepatic impairment and certain drug interactions.
About Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are forms of non-Hodgkin lymphoma, a type of blood cancer, that arise from B lymphocytes. CLL and SLL are essentially the same disease, with the only difference being the location where the cancer primarily occurs.i When most of the cancer cells are located in the peripheral blood and the bone marrow, the disease is referred to as CLL, although the lymph nodes and spleen are often involved. When the cancer cells are located mostly in the lymph nodes, the disease is called SLL.ii According to epidemiological statistics, 88,200 patients are newly diagnosed with lymphoma each year in
About Mantle Cell Lymphoma
Lymphoma is a diverse group of cancers that originate from B-, T- or NK-cells. MCL is typically an aggressive form of non-Hodgkin’s lymphoma (NHL) that arises from B-cells originating in the “mantle zone.”iv According to epidemiological statistics, 88,200 patients are newly diagnosed with lymphoma each year in
About BRUKINSA™ (zanubrutinib)
BRUKINSA (zanubrutinib) is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by
BRUKINSA was granted accelerated approval by the
BRUKINSA is not approved for use outside of
Warnings and Precautions
Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher bleeding events including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 2% of patients treated with BRUKINSA monotherapy. Bleeding events of any grade, including purpura and petechiae, occurred in 50% of patients treated with BRUKINSA monotherapy.
Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.
Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.
Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 23% of patients treated with BRUKINSA monotherapy. The most common Grade 3 or higher infection was pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.
Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.
Grade 3 or 4 cytopenias, including neutropenia (27%), thrombocytopenia (10%) and anemia (8%) based on laboratory measurements, were reported in patients treated with BRUKINSA monotherapy.
Monitor complete blood counts during treatment and treat using growth factor or transfusions, as needed.
Second Primary Malignancies
Second primary malignancies, including non-skin carcinoma, have occurred in 9% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was skin cancer (basal cell carcinoma and squamous cell carcinoma of skin), reported in 6% of patients. Advise patients to use sun protection.
Atrial fibrillation and atrial flutter have occurred in 2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 0.6% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.
Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for at least 1 week after the last dose. Advise men to avoid fathering a child during treatment and for at least 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
The most common adverse reactions in > 10% of patients who received BRUKINSA were neutrophil count decreased (53%), platelet count decreased (39%), upper respiratory tract infection (38%), white blood cell count decreased (30%), hemoglobin decreased (29%), rash (25%), bruising (23%), diarrhea (20%), cough (20%), musculoskeletal pain (19%), pneumonia (18%), urinary tract infection (13%), hematuria (12%), fatigue (11%), constipation (11%), and hemorrhage (10%). The most frequent serious adverse reactions were pneumonia (11%) and hemorrhage (5%).
Of the 118 patients with MCL treated with BRUKINSA, 8 (7%) patients discontinued treatment due to adverse reactions in the trials. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (3.4%). One (0.8%) patient experienced an adverse reaction leading to dose reduction (hepatitis B).
CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.
CYP3A Inducers: Avoid coadministration with moderate or strong CYP3A inducers.
Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.
BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
About the Zanubrutinib Clinical Trial Program
Clinical trials of zanubrutinib include:
- Fully-enrolled Phase 3 ASPEN clinical trial in patients with Waldenström’s macroglobulinemia (WM) comparing zanubrutinib to ibrutinib (NCT03053440), currently the only approved BTK inhibitor for WM;
- Phase 3 SEQUOIA trial comparing zanubrutinib with bendamustine plus rituximab in patients with treatment-naive (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (NCT03336333);
- Phase 3 ALPINE trial comparing zanubrutinib to ibrutinib in patients with relapsed/refractory (R/R) CLL/SLL (NCT03734016);
- Phase 2 trial in combination with GAZYVA® (obinutuzumab) in patients with R/R follicular lymphoma (FL) (NCT03332017);
- Phase 3 trial comparing zanubrutinib and rituximab to bendamustine and rituximab in patients with untreated MCL (NCT04002297);
- Phase 2 MAGNOLIA trial in patients with R/R marginal zone lymphoma (MZL) (NCT03846427);
- Phase 2 ROSEWOOD trial (NCT03332017) in
Chinacomparing obinutuzumab and zanubrutinib vs obinutuzumab alone in treating patients with R/R FL;
- Phase 2 trial (NCT04382586) in the
U.S.comparing zanubrutinib plus supportive care, to placebo plus supportive care for the treatment of patients with COVID-19 disease and pulmonary distress
- Phase 2 trial (NCT03332173) in
Chinain patients with WM; and
- Completed Phase 2 trials in
Chinain patients with R/R MCL (NCT03206970) and R/R CLL/SLL (NCT03206918).
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding BeiGene’s plans and expectations for the commercialization of BRUKINSA, the potential implications of clinical data for patients, and BeiGene’s further advancement of, and anticipated clinical development, regulatory milestones and commercialization of BRUKINSA and its other products and product candidates. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including
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i “Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma” Fact Sheet, Lymphoma Research Foundation. Accessed at: https://www.lymphoma.org/wp-content/uploads/2018/04/LRF_FACTSHEET_CLL_SLL.pdf
ii Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma,” Lymphoma Research Foundation. Accessed at: https://www.lymphoma.org/aboutlymphoma/cll/
iii Chen W, Zheng R , Baade P D , et al. Cancer statistics in
v Li, et al.
vi Philip J. Bierman, James
Source: BeiGene, LTD.