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
Rhea-AI Summary
BeiGene, Ltd. (BGNE) announced that its BTK inhibitor, BRUKINSA™ (zanubrutinib), received approval from the China NMPA for chronic lymphocytic leukemia and mantle cell lymphoma, following priority review. This follows the U.S. accelerated approval in November 2019 for MCL. The approval is based on clinical trials showing significant efficacy, with an overall response rate of 62.6% for CLL/SLL and 83.7% for MCL. The drug's safety profile includes notable adverse reactions, primarily neutropenia and pneumonia. The company aims to launch BRUKINSA as a leading treatment option for these conditions in China.
Positive
- Approval of BRUKINSA for two indications in China enhances BeiGene's product portfolio.
- Significant overall response rates: 62.6% for CLL/SLL and 83.7% for MCL.
- The approval aligns with BeiGene's commitment to advancing treatments for cancer.
Negative
- High incidence of adverse reactions, including a 69.2% rate of Grade ≥3 reactions and 19.8% serious reactions.
- Risks associated with pneumonia as the most common serious adverse event, affecting patient treatment compliance.
News Market Reaction – BGNE
On the day this news was published, BGNE gained 0.42%, reflecting a mild positive market reaction.
Data tracked by StockTitan Argus on the day of publication.
BEIJING, China and CAMBRIDGE, Mass., June 03, 2020 (GLOBE NEWSWIRE) -- BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biotechnology company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, today announced that its BTK inhibitor BRUKINSA™ (zanubrutinib) has received approval from the China National Medical Products Administration (NMPA) in two indications – the treatment of adult patients with chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) who have received at least one prior therapy, and the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Both new drug applications (NDAs) were previously granted priority review by the Center for Drug Evaluation (CDE) of the NMPA.
BRUKINSA received accelerated approval from the U.S. Food and Drug Administration (FDA) as a treatment for MCL in adult patients who have received at least one prior therapy in November 2019.
“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 BeiGene team. With two product approvals covering four indications in China and one in the United States in merely seven months, we continue to focus on execution in advancing our broad portfolio,” commented John V. Oyler, Co-Founder, Chief Executive Officer, and Chairman of BeiGene.
“Following in the footsteps of tislelizumab, BRUKINSA is the second BeiGene internally-developed drug approved in China, another significant expansion in our growing commercial portfolio. These approvals would not have been possible without the many clinicians and patients who participated in our trials and the support of the health authorities,” commented Xiaobin Wu, Ph.D., General Manager of China and President of BeiGene. “We look forward to launching BRUKINSA in China, a potentially best-in-class BTK inhibitor with extensive global data from nine Phase 3 or potentially registration-enabling studies including a head-to-head comparison trial that was recently presented at the American Society of Clinical Oncology Annual Meeting.”
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 China (NCT03206918; BGB-3111-205). Clinical efficacy data in the BRUKINSA label in China, as assessed by independent review committee (IRC) per iwCLL 2008 criteria for CLL and Lugano Classification 2014 for SLL, include an overall response rate (ORR) of
The most common adverse reactions reported in the label in China (≥
“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
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 China (NCT03206970; BGB-3111-206). Clinical efficacy data in the BRUKINSA label in China, as assessed by IRC per Lugano Classification 2014, include the ORR of
The most common adverse reactions (≥
“BRUKINSA has shown promise in hematologic malignancies including in patients with relapsed/refractory MCL. With robust results including a
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 China, with NHL accounting for approximately
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 China, with NHL accounting for approximately
About BRUKINSA™ (zanubrutinib)
BRUKINSA (zanubrutinib) is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad pivotal clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies.
BRUKINSA was granted accelerated approval by the U.S. FDA to treat adult patients with MCL who have received at least one prior therapy in November 2019. This accelerated approval is based on overall response rate (ORR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. BRUKINSA was granted approval in China for the treatment of MCL in adult patients who have received at least one prior therapy and CLL or SLL in adult patients who have received at least one prior therapy in May 2020.
BRUKINSA is not approved for use outside of the United States and China.
IMPORTANT U.S. SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)
Warnings and Precautions
Hemorrhage
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
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.
Infections
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
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.
Cytopenias
Grade 3 or 4 cytopenias, including neutropenia (
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
Cardiac Arrhythmias
Atrial fibrillation and atrial flutter have occurred in
Embryo-Fetal Toxicity
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.
Adverse Reactions
The most common adverse reactions in >
Of the 118 patients with MCL treated with BRUKINSA, 8 (
Drug Interactions
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.
Specific Populations
Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.
INDICATION
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.
Please see full U.S. Prescribing Information at beigene.com/PDF/BRUKINSAUSPI.pdf and Patient Information at beigene.com/PDF/BRUKINSAUSPPI.pdf
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 China comparing 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 China in patients with WM; and
- Completed Phase 2 trials in China in patients with R/R MCL (NCT03206970) and R/R CLL/SLL (NCT03206918).
About BeiGene
BeiGene is a global, commercial-stage biotechnology company focused on discovering, developing, manufacturing, and commercializing innovative medicines to improve treatment outcomes and access for patients worldwide. Our 3,800+ employees in China, the United States, Australia, and Europe are committed to expediting the development of a diverse pipeline of novel therapeutics for cancer. We currently market two internally-discovered oncology products: BTK inhibitor BRUKINSA™ (zanubrutinib) in the United States, and anti-PD-1 antibody tislelizumab in China. We also market or plan to market in China additional oncology products licensed from Amgen Inc., Celgene Logistics Sàrl, a Bristol Myers Squibb (BMS) company, and EUSA Pharma. To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneUSA.
Forward-Looking Statements
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 BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed products and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its technology and drugs; BeiGene's reliance on third parties to conduct drug development, manufacturing and other services; BeiGene’s limited operating history and BeiGene's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates; the impact of the COVID-19 pandemic on the Company’s clinical development, commercial and other operations, as well as those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law.
Investor Contact Media Contact
Craig West Liza Heapes or Vivian Ni
+1 857-302-5189 + 1 857-302-7596
ir@beigene.com media@beigene.com
__________________________
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 China, 2015[J]. CA: A Cancer Journal for Clinicians, 2016, 66(2):115-132.
iv https://www.lls.org/sites/default/files/file_assets/mantlecelllymphoma.pdf
v Li, et al. Journal of Diagnostics Concepts & Practice, 2012,11(2): 111-115
vi Philip J. Bierman, James O. Armitage, in Goldman's Cecil Medicine (Twenty Fourth Edition), 2012.
FAQ
What recent approvals has BeiGene received for BRUKINSA?
What are the clinical efficacy results for BRUKINSA in CLL/SLL?
What is the overall response rate for BRUKINSA in mantle cell lymphoma?
What are the common adverse reactions associated with BRUKINSA?
