On October 20, 2021 BeiGene (NASDAQ: BGNE; HKEX: 06160), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, and Nanolek, a biopharmaceutical company specializing in the production of import-substituting and innovative drugs in Russia, reported that BRUKINSA (zanubrutinib) has received approval from the Russia Ministry of Health for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy (Press release, BeiGene, OCT 20, 2021, View Source [SID1234591604]). BeiGene and Nanolek entered into an exclusive distribution agreement for Nanolek to commercialize BRUKINSA in the Russian Federation.
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"The registration of BRUKINSA (zanubrutinib), a next-generation BTK inhibitor that demonstrated improved clinical benefit while reducing the frequency of certain off-target side effects in MCL, will give physicians and patients another treatment option. BRUKINSA has the potential to give those impacted by MCL in Russia an improved prognosis and a more tolerable therapeutic option," commented Irina Vladimirovna Poddubnaya, Professor, Academician of Russian Academy of Sciences (RAS), and Head of Oncology Department at the Russian Medical Academy of Postgraduate Education.
"This approval reinforces BRUKINSA’s potential as a best-in-class BTK inhibitor for the treatment of hematological malignancies, and we are pleased to make it available to MCL patients in Russia," said Jane Huang, M.D., Chief Medical Officer, Hematology, BeiGene. "We are working to improve outcomes for patients living with cancer, wherever they live, and this year have secured 12 regulatory approvals for BRUKINSA in the United States, Canada, Latin America, and the APAC and EMEA regions."
"We look forward to collaborating with Nanolek to bring a much needed new treatment option to MCL patients in Russia," said Vitaly Sokolinsky, Senior Director, New Market Development, Russia, at BeiGene. "Today’s approval in MCL highlights our continued expansion into Russia, greater Europe and beyond as we bring our expertise to new markets around the world."
"We’re proud of this significant achievement for patients and look forward to contributing to BRUKINSA’s growing global footprint through our strong collaboration with BeiGene," added Vladimir Khristenko, President of Nanolek. "Together, we are committed to delivering innovative therapies for the benefit of people impacted by cancer in Russia."
Marketing approval for BRUKINSA for the treatment of MCL in Russia is based on results from two single-arm clinical trials. Across both trials, as assessed by independent review committee (IRC) per 2014 Lugano Classification, BRUKINSA achieved an overall response rate (ORR) of 83.7%, defined as the combined rate of complete responses (CRs) and partial responses (PRs).
Of the 118 patients with MCL who received at least one prior therapy and received BRUKINSA treatment, serious adverse reactions occurred in 36 patients (31%), with the most frequent being pneumonia (11%) and bleeding (5%). Eight patients (7%) discontinued treatment due to adverse reactions in the trials, with the most frequent being pneumonia (3.4%), and one patient (0.8%) experienced an adverse reaction that led to dose reduction.
The recommended dose of BRUKINSA is either 160 mg twice daily or 320 mg once 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 Mantle Cell Lymphoma (MCL)
MCL is rare form of non-Hodgkin lymphoma (NHL), representing about 5% of all NHL cases.1 It develops in the outer edge of a lymph node called the mantle zone.1 Mantle cell lymphoma occurs more often in men than in women.1 It is usually diagnosed in people in their early 60s.1 MCL has a poor prognosis, with a median survival of three to four years, and is often diagnosed at a later stage of disease.2 In Russia, there are more than 1,000 new cases of MCL diagnosed each year.3
About BRUKINSA
BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.
BRUKINSA is approved in the following indications and regions:
For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (United States, November 2019)*;
For the treatment of MCL in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of relapsed or refractory MCL (United Arab Emirates, February 2021);
For the treatment of Waldenström’s macroglobulinemia (WM) in adult patients (Canada, March 2021);
For the treatment of adult patients with WM who have received at least one prior therapy (China, June 2021)**;
For the treatment of MCL in adult patients who have received at least one prior therapy (Canada, July 2021);
For the treatment of MCL in adult patients who have received at least one prior therapy (Chile, July 2021);
For the treatment of adult patients with MCL who have received at least one previous therapy (Brazil, August 2021);
For the treatment of adult patients with WM (United States, August 2021);
For the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen (United States, September 2021)*;
For the treatment of adult patients with MCL who have received at least one previous therapy (Singapore, October 2021);
For the treatment of MCL in patients who have received at least one prior therapy (Israel, October 2021);
For the treatment of adult patients with WM who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy (Australia, October 2021);
For the treatment of adult patients with MCL who have received at least one prior therapy (Australia, October 2021); and
For the treatment of adult patients with MCL who have received at least one previous therapy (Russia, October 2021).
To date, more than 30 marketing authorization applications in multiple indications have been submitted in the United States, China, the European Union, and more than 20 other countries or regions.
* This indication was 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.
** This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.
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 hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.4% of patients treated with BRUKINSA monotherapy. Hemorrhage events of any grade occurred in 35% 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.
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 27% of patients, most commonly 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.
Cytopenias
Grade 3 or 4 cytopenias, including neutropenia (26%), thrombocytopenia (11%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 13% of patients, and Grade 4 thrombocytopenia occurred in 3.6% of patients.
Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.
Second Primary Malignancies
Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 8% of patients. Other second primary malignancies included malignant solid tumors (4.0%), melanoma (1.7%) and hematologic malignancies (1.2%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.
Cardiac Arrhythmias
Atrial fibrillation and atrial flutter were reported in 3.2% 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 1.1% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.
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 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 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, including laboratory abnormalities, in ≥ 30% of patients who received BRUKINSA (N = 847) included decreased neutrophil count (54%), upper respiratory tract infection (47%), decreased platelet count (41%), hemorrhage (35%), decreased lymphocyte count (31%), rash (31%) and musculoskeletal pain (30%).
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.
Please see full U.S. Prescribing Information at www.beigene.com/PDF/BRUKINSAUSPI.pdf and Patient Information at www.beigene.com/PDF/BRUKINSAUSPPI.pdf.
BeiGene Oncology
BeiGene is committed to advancing hematology, immuno-oncology and targeted therapies in order to bring impactful and affordable medicines to patients across the globe. We have a growing R&D team of approximately 2,300 colleagues dedicated to advancing more than 90 clinical trials involving more than 13,000 patients and healthy subjects. Our expansive portfolio is directed by a predominantly internalized clinical development team supporting trials in more than 40 countries or regions. We currently market three medicines discovered and developed in our labs: BTK inhibitor BRUKINSA in the United States, China, Canada, Australia and additional international markets; and non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab and PARP inhibitor pamiparib in China. BeiGene has a high quality, innovative science and medicine organization and is a leader in China with a large oncology focused commercial team.
BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen and Bristol Myers Squibb. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, EUSA Pharma, Mirati Therapeutics, Seagen, and Zymeworks. BeiGene has also entered into a collaboration with Novartis granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.