This marks the third FDA approval for BRUKINSA
and first approval in marginal zone lymphoma
Twenty percent of patients achieved complete
remission with single-agent BRUKINSA
BRUKINSA was generally well-tolerated,
consistent with its known safety profile
BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a global
biotechnology company focused on developing and commercializing
innovative medicines worldwide, today announced that BRUKINSA®
(zanubrutinib) has received accelerated approval from the U.S. Food
and Drug Administration (FDA) for the treatment of adult patients
with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who
have received at least one anti-CD20-based regimen.
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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.
“We are excited about the FDA’s approval for BRUKINSA in
patients with previously treated marginal zone lymphoma, a
significant milestone that was made possible by the diligent
BeiGene team, the dedicated investigators, and the participating
patients and their families. The MAGNOLIA trial results provided
additional evidence that the selective design of BRUKINSA can be
translated to improved treatment outcomes for these patients,” said
Jane Huang, M.D., Chief Medical Officer, Hematology at BeiGene.
“The ongoing evaluation of BRUKINSA in its broad global clinical
program will enable us to further understand this potentially
best-in-class BTK inhibitor and its impact on patients. Since the
initial FDA approval in November 2019, BRUKINSA has been granted 12
approvals in four indications globally. We will continue to execute
on our mission to improve access to innovative and quality
treatments for cancer patients worldwide.”
“BTK plays a critical role in B-cell receptor signaling, a
driver in the development of marginal zone lymphoma. In the
MAGNOLIA trial, BRUKINSA demonstrated impressive overall response
and complete remission rates, with responses observed in all MZL
subtypes. In addition, this next-generation BTK inhibitor was
well-tolerated in these patients, with low rate of discontinuation
due to adverse reactions. We are optimistic that BRUKINSA will
bring clinically meaningful benefit to patients with relapsed or
refractory marginal zone lymphoma,” said Stephen Opat, FRACP,
FRCPA, MBBS, Director of Clinical Hematology at Monash Health, Head
of Department of Hematology at Monash University, and lead
principal investigator of the MAGNOLIA trial.
“The approval of BRUKINSA offers patients with relapsed and
refractory marginal zone lymphoma a new treatment option and new
hope for improving patient outcomes,” commented Meghan Gutierrez,
Chief Executive Officer of the Lymphoma Research Foundation.
The FDA approval of BRUKINSA is based on efficacy results from
two single-arm clinical trials, with ORR as assessed by independent
review committee (IRC) per 2014 Lugano Classification as the
primary endpoint.
In the multicenter, pivotal Phase 2 MAGNOLIA trial (NCT03846427)
in patients with R/R MZL who received at least one anti-CD20-based
regimen, a total of 66 patients were evaluated, including 26 with
extranodal subtype, 26 with nodal subtype, 12 with splenic subtype,
and four with unknown subtype. Based on assessment using CT scan,
the ORR was 56% (95% CI: 43, 68) with a complete response (CR) rate
of 20%; based on assessment prioritizing PET-CT scan, the ORR was
67% (95% CI: 54, 78) with a CR rate of 26%. The median duration of
response (DoR) was not reached at the median follow-up time of 8.3
months, with 85% of responders still in remission at 12 months (95%
CI: 67, 93). Responses were observed in all MZL subtypes.
In the global Phase 1/2 trial of BGB-3111-AU-003 (NCT02343120),
a total of 20 patients were evaluated, including nine with
extranodal subtype, five with nodal subtype, and six with splenic
subtype. Based on assessment using CT scan, the ORR was 80% (95%
CI: 56, 94) with a CR rate of 20%. The median DoR was not reached
at the median follow-up time of 31.4 months, with 72% of responders
still in remission at 12 months (95% CI: 40, 88).
The most common (≥30%) adverse reactions, including laboratory
abnormalities, in the pooled safety population of 847 patients were
decreased neutrophil count, upper respiratory tract infection,
decreased platelet count, hemorrhage, decreased lymphocyte count,
rash, and musculoskeletal pain.
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 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 Waldenstr�m’s macroglobulinemia (WM) in
adult patients (Canada, March 2021);
- Registered and reimbursed for the treatment of MCL in patients
who have received at least one prior therapy (Israel, April
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); and
- 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)*.
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 best and first-in-class
clinical candidates internally or with like-minded partners to
develop impactful and affordable medicines for 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 volunteers. Our
expansive portfolio is directed by a predominantly internalized
clinical development team supporting trials in more than 40
countries. Hematology-oncology and solid tumor targeted therapies
and immuno-oncology are key focus areas for the Company, with both
mono- and combination therapies prioritized in our research and
development. We currently market three medicines discovered and
developed in our labs: BTK inhibitor BRUKINSA in the United States,
China, Canada, and additional international markets; and
non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab and
PARP inhibitor pamiparib in China.
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.
About BeiGene
BeiGene is a global, science-driven biotechnology company
focused on developing innovative and affordable medicines to
improve treatment outcomes and access for patients worldwide. With
a broad portfolio of more than 40 clinical candidates, we are
expediting development of our diverse pipeline of novel
therapeutics through our own capabilities and collaborations. We
are committed to radically improving access to medicines for two
billion more people by 2030. BeiGene has a growing global team of
over 7,000 colleagues across five continents. To learn more about
BeiGene, please visit www.beigene.com and follow us on Twitter at
@BeiGeneGlobal.
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 plan for the advancement, and anticipated clinical
development, regulatory milestones and commercialization of
BRUKINSA, the potential for BRUKINSA to provide improved clinical
benefit to patients, and BeiGene’s plans, commitments, aspirations,
and goals under the headings “BeiGene Oncology” and “About
BeiGene”. 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 medicines and drug candidates, if approved;
BeiGene's ability to obtain and maintain protection of intellectual
property for its medicines and technology; BeiGene's reliance on
third parties to conduct drug development, manufacturing and other
services; BeiGene’s limited experience in obtaining regulatory
approvals and commercializing pharmaceutical products and its
ability to obtain additional funding for operations and to complete
the development and commercialization of its drug candidates and
achieve and maintain profitability; the impact of the COVID-19
pandemic on the BeiGene’s clinical development, regulatory,
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.
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BeiGene Contacts Investor Contact Gabrielle Zhou
+86 10-5895-8058 or +1 857-302-5189 ir@beigene.com
Media Contact Liza Heapes or Vivian Ni +1 857-302-5663 or
+1 857-302-7596 media@beigene.com
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