- Submission seeks approval for BRUKINSA in
combination with obinutuzumab as a treatment for relapsed or
refractory follicular lymphoma
BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global
biotechnology company, today announced the U.S. Food and Drug
Administration (FDA) has accepted for review the Company’s
supplemental new drug application (sNDA) for BRUKINSA®
(zanubrutinib) in combination with obinutuzumab for the treatment
of adult patients with relapsed or refractory (R/R) follicular
lymphoma (FL) after at least two prior lines of therapy. BRUKINSA
was previously granted Fast Track and Orphan designation for this
indication. The FDA has assigned a target action date in the first
quarter of 2024, under the Prescription Drug User Fee Act.
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Mehrdad Mobasher, M.D., M.P.H., Chief
Medical Officer, Hematology at BeiGene commented that BRUKINSA is
the first Bruton's tyrosine kinase inhibitor to demonstrate
efficacy in follicular lymphoma and BeiGene plans to continue
worldwide regulatory submissions based on the ROSEWOOD results
(Photo: Business Wire)
“Follicular lymphoma is the most common slow-growing non-Hodgkin
lymphoma, but there are limited treatment options for patients
whose condition has progressed after two lines of therapy. We are
therefore pleased that BRUKINSA is the first Bruton's tyrosine
kinase inhibitor to demonstrate efficacy in follicular lymphoma and
plan to continue worldwide regulatory submissions based on the
ROSEWOOD results,” said Mehrdad Mobasher, M.D., M.P.H., Chief
Medical Officer, Hematology. “Importantly, we are grateful to the
people living with relapsed or refractory follicular lymphoma who
chose to participate in the ROSEWOOD study.”
The sNDA filing in FL is based on results from the Phase 2
ROSEWOOD study (NCT03332017) that included 217 patients with
pre-treated R/R non-Hodgkin FL (145 receiving BRUKINSA plus
obinutuzumab and 72 patients receiving obinutuzumab monotherapy).
In the primary ROSEWOOD analysis at a median follow-up of 12.5
months, BRUKINSA plus obinutuzumab demonstrated superior efficacy
to obinutuzumab monotherapy with a 68.3% overall response rate
(ORR) versus 45.8% respectively (p = 0.0017). Responses were
durable with 18-month landmark duration of response (DOR) of
69.3%.
Safety results from the ROSEWOOD study were consistent with
previous studies of both medicines. The most common treatment
emergent adverse events reported in the primary analysis for the
combination arm compared with the obinutuzumab alone arm were
diarrhea (18.2% vs 16.9%), fatigue (15.4% vs 14.1%), and pyrexia
(13.3% vs 19.7%).i
Longer-term data included in the sNDA demonstrated the efficacy
benefit for BRUKINSA plus obinutuzumab persisted at a median
follow-up of 20.2 months, with an ORR of 69.0% versus 45.8% for
obinutuzumab monotherapy (p = 0.0012). Additionally, the
combination of BRUKINSA and obinutuzumab reduced the risk of
disease progression or death by 50% compared with obinutuzumab
alone (HR 0.50; 95% CI 0.33-0.75).ii
BeiGene currently has submissions for BRUKINSA in R/R FL under
review by regulatory authorities in the European Union and China.
BeiGene’s submission for BRUKINSA in R/R FL is under review by
regulatory authorities in Canada, Switzerland, and the United
Kingdom as part of the Access Consortium New Active Substance
Work-sharing Initiative.
BRUKINSA is approved in more than 65 markets including the U.S.,
China, European Union, Great Britain, Canada, Australia, South
Korea, and Switzerland in selected indications and under
development for additional approvals globally. The product
information may differ from country to country. Prescribers should
consult the product information approved in their respective
country. The global BRUKINSA development program includes more than
4,900 subjects enrolled to-date in 29 countries and regions.
About ROSEWOOD
ROSEWOOD is a randomized, open-label, Phase 2 study comparing
BRUKINSA plus obinutuzumab to obinutuzumab alone in patients with
R/R FL who have received two or more lines of therapy. The primary
endpoint was ORR assessed by independent central review (ICR)
according to the Lugano classification. Select secondary endpoints
include investigator-assessed ORR, ICR-reviewed and
investigator-assessed DOR and progression-free survival, overall
survival, and analysis of safety.
About BRUKINSA® (zanubrutinib)
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.
IMPORTANT U.S. INDICATIONS AND SAFETY INFORMATION FOR
BRUKINSA (ZANUBRUTINIB)
Indications
BRUKINSA is a kinase inhibitor indicated for the treatment of
adult patients with:
- Chronic lymphocytic leukemia (CLL) or small lymphocytic
lymphoma (SLL)
- Waldenstr�m’s macroglobulinemia (WM)
- Mantle cell lymphoma (MCL) who have received at least one prior
therapy
- Relapsed or refractory marginal zone lymphoma (MZL) who have
received at least one anti-CD20-based regimen
The MCL and MZL indications are approved under accelerated
approval based on overall response rate. Continued approval for
these indications may be contingent upon verification and
description of clinical benefit in confirmatory trials.
Warnings and Precautions
Hemorrhage
Fatal and serious hemorrhage has 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 3.6% of
patients treated with BRUKINSA monotherapy in clinical trials, with
fatalities occurring in 0.3% of patients. Bleeding of any grade,
excluding purpura and petechiae, occurred in 30% of patients.
Bleeding has occurred in patients with and without concomitant
antiplatelet or anticoagulation therapy. Coadministration 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 infections) and opportunistic infections have occurred in
patients with hematological malignancies treated with BRUKINSA
monotherapy. Grade 3 or higher infections occurred in 24% of
patients, most commonly pneumonia (11%), with fatal infections
occurring in 2.9% of patients. Infections due to hepatitis B virus
(HBV) reactivation have occurred.
Consider prophylaxis for herpes simplex virus, pneumocystis
jirovecii 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 (22%),
thrombocytopenia (8%) and anemia (7%) based on laboratory
measurements, developed in patients treated with BRUKINSA
monotherapy. Grade 4 neutropenia occurred in 11% of patients, and
Grade 4 thrombocytopenia occurred in 2.8% 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 13% of patients treated with BRUKINSA monotherapy. The
most frequent second primary malignancy was non-melanoma skin
cancer reported in 7% of patients. Other second primary
malignancies included malignant solid tumors (5%), melanoma (1.2%),
and hematologic malignancies (0.5%). Advise patients to use sun
protection and monitor patients for the development of second
primary malignancies.
Cardiac Arrhythmias
Serious cardiac arrhythmias have occurred in patients treated
with BRUKINSA. Atrial fibrillation and atrial flutter were reported
in 3.7% of 1550 patients treated with BRUKINSA monotherapy,
including Grade 3 or higher cases in 1.7% of patients. Patients
with cardiac risk factors, hypertension, and acute infections may
be at increased risk. Grade 3 or higher ventricular arrhythmias
were reported in 0.2% of patients.
Monitor for signs and symptoms of cardiac arrhythmias (e.g.,
palpitations, dizziness, syncope, dyspnea, chest discomfort),
manage appropriately, and consider the risks and benefits of
continued BRUKINSA treatment.
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
In this pooled safety population, the most common adverse
reactions, including laboratory abnormalities, in ≥30% of patients
who received BRUKINSA (N=1550) included decreased neutrophil count
(42%), upper respiratory tract infection (39%), decreased platelet
count (34%), hemorrhage (30%), 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 strong or
moderate CYP3A inducers. Dose adjustment may be recommended with
moderate 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
About BeiGene
BeiGene is a global biotechnology company that is discovering
and developing innovative oncology treatments that are more
affordable and accessible to cancer patients worldwide. With a
broad portfolio, we are expediting development of our diverse
pipeline of novel therapeutics through our internal capabilities
and collaborations. We are committed to radically improving access
to medicines for far more patients who need them. Our growing
global team of more than 9,400 colleagues spans five continents,
with administrative offices in Beijing, China; Cambridge, U.S.; and
Basel, Switzerland. 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 advancement, anticipated clinical development, regulatory
submissions and commercialization of zanubrutinib, particularly as
a treatment for R/R FL; and BeiGene’s plans, commitments,
aspirations, and goals under the heading “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; and the impact of the COVID-19
pandemic on BeiGene’s clinical development, regulatory, commercial,
manufacturing, 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.
i Zinzani, P. L., Mayer, J., Auer, R., Bijou, F., De Oliveira,
A. C., Flowers, C., ... & Trotman, J. (2022). Zanubrutinib plus
obinutuzumab (ZO) versus obinutuzumab (O) monotherapy in patients
(pts) with relapsed or refractory (R/R) follicular lymphoma (FL):
Primary analysis of the phase 2 randomized ROSEWOOD trial. DOI:
10.1200/JCO.2022.40.16_suppl.7510 Journal of Clinical Oncology 40,
no. 16_suppl (June 01, 2022) 7510-7510.
ii Nastoupil, L. J., Song, Y., Sehn, L. H., Sarkozy, C.,
Zinzani, P. L., Salar, A., ... & Trotman, J. (2023). MAHOGANY:
A Phase 3 Trial of Zanubrutinib Plus Anti-CD20 Antibodies vs
Lenalidomide Plus Rituximab in Patients With Relapsed or Refractory
Follicular or Marginal Zone Lymphoma. DOI:
10.1200/JCO.2023.41.16_suppl.TPS7590 Journal of Clinical Oncology
41, no. 16_suppl (June 01, 2023) TPS7590-TPS7590.
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Investor: Liza Heapes +1 857-302-5663 ir@beigene.com
Media: Kyle Blankenship +1 667-351-5176
media@beigene.com
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