BeiGene’s European commercial team is preparing
to launch BRUKINSA, the company’s first medicine submitted for
marketing authorization in the EU, upon approval
The CHMP recommendation is based on results
from the Phase 3 ASPEN trial, in which BRUKINSA demonstrated a
numerically higher very good partial response rate (VGPR) and a
favorable safety profile compared to ibrutinib
BeiGene (NASDAQ: BGNE; HKEX: 06160) today announced the
Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency (EMA) has adopted a positive opinion,
recommending approval of BRUKINSA (zanubrutinib) for the treatment
of adult patients with Waldenstr�m’s macroglobulinemia (WM) who
have received at least one prior therapy or first-line treatment
for patients unsuitable for chemo-immunotherapy.
“Bruton’s tyrosine kinase (BTK) inhibitors have emerged as a
promising treatment for WM, yet treatment discontinuation due to
lack of response or side effects remains a concern,” said Prof.
Christian Buske, Medical Director at the University Hospital Ulm,
Germany, and a trial investigator of the ASPEN study. “The ASPEN
trial demonstrated that BRUKINSA provided deep and durable
responses and offered substantial improvements in safety and
tolerability over standard therapy. Patients in Europe with WM may
soon have a new treatment option that can offer improved
outcomes.”
The positive CHMP opinion is based on results from the
randomized, Phase 3 ASPEN clinical trial, evaluating BRUKINSA
compared to ibrutinib in patients with relapsed or refractory (R/R)
or treatment-naïve (TN) WM who are unsuitable for
chemo-immunotherapy. Based on the modified Sixth International
Workshop on Waldenstr�m’s Macroglobulinemia (IWWM-6) response
criteria (Treon 2015), the combined complete response (CR) +VGPR
rate in the overall intention-to-treat (ITT) population was 28.4%
with BRUKINSA (95% CI: 20, 38), compared to 19.2% with ibrutinib
(95% CI: 12, 28). While this difference was not statistically
significant, BRUKINSA did achieve numerically higher VGPR rates and
trends towards increased response quality.1
BRUKINSA demonstrated a more favorable safety profile compared
to ibrutinib with lower frequency of certain adverse events,
including atrial fibrillation or flutter (2.0% vs. 15.3%) minor
bleeding (48.5% vs 59.2%) and major hemorrhage (5.9% vs 9.2%).1 Of
the 101 patients with WM treated with BRUKINSA, four percent of
patients discontinued due to adverse events, and adverse events
leading to dose reduction occurred in 14% of patients.
“The positive CHMP opinion reflects BRUKINSA’s potential role in
the WM therapeutic landscape as a selective inhibitor designed to
deliver sustained and continuous inhibition of BTK, offering
patients the potential for reduced frequency of certain
cardiovascular events like atrial fibrillation compared to
ibrutinib, and underscores our bold approach to R&D,” said Jane
Huang, M.D., Chief Medical Officer, Hematology, at BeiGene. “We are
committed to advancing the global registration of BRUKINSA and, if
approved, believe it will become the preferred BTK inhibitor for
patients with WM.”
“We have a strong team in Europe who are excited for the
opportunity to further work with the many investigators who have
participated in BRUKINSA trials conducted in Europe to-date.
Looking to the future, we have built a team in Europe and they are
poised to help patients access BRUKINSA following its expected
approval,” said Gerwin Winter, Senior Vice President, Head of
Commercial, Europe, at BeiGene. “We look forward to continuing our
work with the European health authorities to bring BRUKINSA to
patients living with this rare, incurable blood cancer.”
Following the CHMP positive opinion, the European Commission
will consider BeiGene’s marketing application, with a final
decision expected within 67 days of receipt of the CHMP opinion.
The decision will be applicable to all 27 member states of the EU
plus Iceland and Norway.
About Waldenstr�m’s Macroglobulinemia
WM is a rare lymphoma representing approximately one percent of
all non-Hodgkin’s lymphomas and typically progresses slowly after
diagnosis.2 The disease usually affects older adults and is
primarily found in the bone marrow, although lymph nodes and the
spleen may be involved.3 Throughout Europe, the estimated incidence
rate of WM is approximately seven for every one million men and
four for every one million women.4
About the ASPEN trial
The Phase 3 randomized, open-label, multicenter ASPEN clinical
trial (NCT03053440) evaluated zanubrutinib versus ibrutinib in
people with relapsed or refractory (R/R) or treatment-naïve (TN)
WM. The primary objective was to establish superiority of
zanubrutinib compared to ibrutinib as demonstrated by the
proportion of people achieving complete response (CR) or very good
partial response (VGPR). Secondary endpoints included major
response rate, duration of response and progression-free survival,
and safety, measured by incidence, timing and severity of
treatment-emergent adverse events. The pre-specified analysis
populations for the trial included the overall population (n=201)
and R/R patients (n=164). Exploratory endpoints included quality of
life measures.
The study includes two cohorts, a randomized cohort (cohort 1)
consisting of 201 patients with a MYD88 mutation (MYD88MUT) and a
non-randomized cohort (cohort 2) in which 28 patients with MYD88
wild-type (MYD88WT) received zanubrutinib because they have
historically responded poorly to ibrutinib therapy.
The randomized cohort 1 enrolled 102 patients (including 83
relapsed or refractory (R/R) patients and 19 TN (patients) in the
zanubrutinib arm and 99 patients (including 81 R/R patients and 18
TN patients) in the ibrutinib arm. Patients in the zanubrutinib arm
were assigned to receive zanubrutinib 160 mg twice daily (BID) and
patients in the ibrutinib arm received 420 mg of ibrutinib once
daily (QD).
Results of cohort 2 were previously presented at the 24th
Congress of European Hematology Association (EHA) and showed an
overall response rate (ORR) of 80.8%, a major response rate (MRR;
partial response or better) of 53.8% and a VGPR rate of 23.1%.
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
future development and potential commercialization of BRUKINSA in
the European Union and other markets, the potential for BRUKINSA to
be a best-in-class BTK inhibitor, the potential for zanubrutinib to
provide improved clinical benefit with advantages in safety, and
the potential commercial opportunity for BRUKINSA. 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
medicines and technology; 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.
References:
1. Tam, et al. A randomized phase 3 trial of zanubrutinib vs
ibrutinib in symptomatic Waldenstr�m macroglobulinemia: the ASPEN
study. Blood. October 2020. 136(18): 2038-2050.
2. Lymphoma Research Foundation. Getting the Facts: Waldenstr�m
Macroglobulinemia. Available at
https://lymphoma.org/wp-content/uploads/2020/09/LRF_Factsheet_Waldenstro%CC%88m-Macroglobulinemia_090920.pdf.
Accessed April 2021.
3. Lymphoma Research Foundation. Available at
https://lymphoma.org/aboutlymphoma/nhl/wm/. Accessed December
2020.
4. Buske, C, et al. Treatment and outcome patterns in European
patients with Waldenstr�m’s macroglobulinaemia: a large,
observational, retrospective chart review. The Lancet Haematology
2018; 5: e0299-309.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20210917005068/en/
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
BeiGene (NASDAQ:BGNE)
Historical Stock Chart
From Mar 2024 to Apr 2024
BeiGene (NASDAQ:BGNE)
Historical Stock Chart
From Apr 2023 to Apr 2024