Matching adjusted indirect comparison addresses
key questions and limitations associated with previously presented
analysis and suggests efficacy advantage of BRUKINSA vs
acalabrutinib
BeiGene, Ltd. (Nasdaq: BGNE; HKEX: 06160; SSE: 688235), a global
oncology company, today announced a new matching adjusted indirect
comparison (MAIC) of the efficacy of BRUKINSA® (zanubrutinib)
versus acalabrutinib in relapsed or refractory (R/R) chronic
lymphocytic leukemia (CLL) based on data from the Phase 3 ALPINE
and Phase 3 ASCEND trials. The analysis suggests a progression-free
survival and complete response advantage for BRUKINSA versus
acalabrutinib, as well as potentially improved overall survival.
These data will be presented during the 28th Annual International
Congress on Hematologic Malignancies® in Miami from February 29 -
March 3.
“The CLL landscape is evolving rapidly, and this MAIC provides
timely comparative effectiveness data for physicians, and
reinforces zanubrutinib role as a foundational CLL treatment via a
robust evaluation of the efficacy in the ASCEND and ALPINE studies;
the presented analysis not only accounts for differences in key
patient characteristics, but also clarifies the impact COVID-19 may
have had on study outcomes,” said Mazyar Shadman, M.D. M.P.H, Study
Author and Innovators Network Endowed Chair, Associate Professor of
Hematology and Oncology, Lymphoid Malignancies and Immunotherapy,
Fred Hutch Cancer Center and University of Washington.
“Head-to-head randomized clinical trials are the gold standard when
it comes to evaluating the potential impact of individual
treatments for patients. MAICs are intended to be
hypothesis-generating, provided they are conducted with appropriate
rigor to minimize potential biases.”
In this MAIC, individual patient-level data from ALPINE was
matched against the aggregate data from ASCEND. An unanchored MAIC
was used due to the lack of a common comparator arm between the
ALPINE and ASCEND trials. Given the differences in the timing of
the studies, with respect to the onset of the COVID-19 pandemic,
the analysis adjusted for the impact of COVID-19 in the ALPINE
study.
In a previously published MAIC of BRUKINSA versus
acalabrutinib,1 there were significant limitations that precluded a
robust efficacy comparison, including the exclusion of data from
the final analysis of ALPINE, lack of adjustment for the impact of
COVID-19 on the outcomes, lack of adjustment for key differences in
patient characteristics, the effective sample size, and the
exclusion of complete response rate and overall survival from the
analysis.
“BeiGene is committed to continuing to further our understanding
of the efficacy and safety of our therapies and their potential to
help patients among other options,” said Mehrdad Mobasher, M.D.,
M.P.H., Chief Medical Officer, Hematology at BeiGene. “This MAIC
addresses key questions raised in a previously published analysis,
presenting a more holistic representation of the efficacy
associated with BRUKINSA versus acalabrutinib in relapsed or
refractory chronic lymphocytic leukemia setting.”
BRUKINSA is the only Bruton’s tyrosine kinase (BTK) inhibitor to
demonstrate progression-free survival superiority vs ibrutinib in
R/R CLL, as observed in the ALPINE trial.2 Acalabrutinib has
demonstrated improvement in progression-free survival vs rituximab
plus idelalisib/bendamustine in R/R CLL in the ASCEND trial and has
also demonstrated progression-free survival noninferiority vs
ibrutinib R/R CLL patients with chromosome 17p or 11q deletions in
the ELEVATE-RR trial.3,4
The MAIC suggests that investigator-assessed progression-free
survival was improved for BRUKINSA versus acalabrutinib in both the
unadjusted population (HR=0.77 [95%CI: 0.55-1.07]), as well as the
base case adjusted population (HR=0.68 [95%CI: 0.46-0.99]).
Additionally, the odds ratio (OR) for complete response favored
BRUKINSA over acalabrutinib in the unadjusted (OR=2.88 [95%CI:
1.18-7.02]) and base case adjusted populations (OR=2.90; [95%CI:
1.13-7.43]). Results for the sensitivity analysis were consistent
with the base case. The overall survival trend remained
consistently in favor of BRUKINSA. For additional details of the
analysis, please refer to the full poster presentation.
While MAIC analyses can be hypotheses-generating, in the absence
of head-to-head data, the safety of a drug may be best evaluated
using all available evidence across indications. A recent
independent Mayo Clinic meta-analysis of 61 trials involving 6,959
patients who received ibrutinib plus an anti-CD20 antibody,
acalabrutinib, and BRUKINSA extensively analyzed the adverse event
profiles of the two therapies across several indications and
reported key differences in the safety profiles of the two
treatments.5
BRUKINSA is approved in 70 markets, including the U.S., China,
EU, Great Britain, Canada, Australia, South Korea and Switzerland
in selected indications, and it is under development for additional
indications globally. The global BRUKINSA development program
includes more than 5,000 subjects enrolled to date in 29 countries
and regions.
About MAICs
Match adjusted indirect comparisons are intended to be
hypothesis generating, and do not establish superior efficacy or
safety of one drug over another. Results should be viewed in the
context of study limitations and available clinical data.
About ALPINE
ALPINE is a randomized, global, Phase 3 trial (NCT03734016)
comparing BRUKINSA with ibrutinib in previously treated patients
with R/R CLL or small lymphocytic lymphoma (SLL). In the trial, a
total of 652 patients across Europe (60%), the United States (17%),
China (14%), and New Zealand and Australia (9%) were randomized to
receive BRUKINSA (160 mg orally twice daily) or ibrutinib (420 mg
orally once daily) until disease progression, death, or
unacceptable toxicity.
The primary endpoint of overall response rate (ORR) was assessed
by both investigator and independent review committee (IRC) using
the modified 2008 iwCLL guidelines, with modification for
treatment-related lymphocytosis for patients with CLL, and as per
Lugano Classification for non-Hodgkin’s lymphoma for patients with
SLL. Key secondary endpoints included PFS and the rate of atrial
fibrillation or flutter; other secondary endpoints included
duration of response, overall survival, and incidence of adverse
events. There was a pre-specified hierarchical testing of
non-inferiority followed by superiority for ORR as assessed by
investigator and IRC. As ORR superiority was demonstrated,
progression-free survival was tested for noninferiority and
superiority under hierarchical testing.
In an extended follow-up of the ALPINE study at a median
follow-up of 39 months, BRUKINSA showed sustained PFS improvement
versus ibrutinib (HR: 0.68 [95% CI, 0.53-0.86] P=0.0011) among R/R
CLL/SLL patients, with durable PFS benefit observed across key
subgroups, including patients with 17p deletion or TP53 mutation
(HR: 0.52 [95% CI, 0.33-0.83] P=0.0047). PFS benefit was consistent
across multiple sensitivity analyses, demonstrating that PFS
advantage with BRUKINSA was primarily driven by efficacy, and not
better tolerability. The overall safety and tolerability profile
was consistent with previous ALPINE analyses, including
persistently lower rates of cardiovascular events reported with
BRUKINSA. The most commonly reported treatment emergent adverse
events (≥20%) with BRUKINSA were COVID-19-related infection,
neutropenia, hypertension, and upper respiratory tract
infection.6
About BRUKINSA® (zanubrutinib)
BRUKINSA is a small molecule inhibitor of BTK designed to
deliver complete and sustained inhibition of the BTK protein by
optimizing bioavailability, half-life, and selectivity. With
differentiated pharmacokinetics compared with other approved BTK
inhibitors, BRUKINSA has been demonstrated to inhibit the
proliferation of malignant B cells within a number of
disease-relevant tissues.
U.S. Indications and Important Safety Information for
BRUKINSA (zanubrutinib)
INDICATIONS
BRUKINSA is a kinase inhibitor indicated for the treatment of
adult patients with:
- Chronic lymphocytic leukemia or small lymphocytic lymphoma
- Waldenstr�m’s macroglobulinemia
- 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.
IMPORTANT SAFETY INFORMATION
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
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 (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 and U.S. Patient
Information.
About BeiGene
BeiGene is a global oncology company that is discovering and
developing innovative 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
10,000 colleagues spans five continents, with administrative
offices in Basel, Beijing, and Cambridge, U.S. To learn more about
BeiGene, please visit www.beigene.com and follow us on LinkedIn and
X (formerly known as Twitter).
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
the potential of BeiGene’s therapies to help patients; the efficacy
and safety of BRUKINSA versus acalabrutinib in patients with R/R
CLL; 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,
commercialization, and other services; BeiGene’s limited experience
in obtaining regulatory approvals and commercializing
pharmaceutical products; BeiGene’s ability to obtain additional
funding for operations and to complete the development of its drug
candidates and achieve and maintain profitability; and those risks
more fully discussed in the section entitled “Risk Factors” in
BeiGene’s most recent annual report on Form 10-K, 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.
To access BeiGene media resources, please visit our News &
Media site.
1 Kittai AS, et al. A matching-adjusted indirect comparison of
acalabrutinib versus zanubrutinib in relapsed or refractory chronic
lymphocytic leukemia. Am J Hematol. 2023 Dec;98(12):E387-E390. doi:
10.1002/ajh.27110. Epub 2023 Oct 9. PMID: 37811799.
2 Brown JR, et al. Zanubrutinib or Ibrutinib in Relapsed or
Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2023 Jan
26;388(4):319-332. doi: 10.1056/NEJMoa2211582. Epub 2022 Dec 13.
PMID: 36511784.
3 Ghia P, et al. ASCEND: Phase III, Randomized Trial of
Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus
Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. J
Clin Oncol. 2020 Sep 1;38(25):2849-2861. doi: 10.1200/JCO.19.03355.
Epub 2020 May 27. PMID: 32459600.
4 Sharman JP, et al. Acalabrutinib with or without obinutuzumab
versus chlorambucil and obinutuzmab for treatment-naive chronic
lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase
3 trial. Lancet. 2020 Apr 18;395(10232):1278-1291. doi:
10.1016/S0140-6736(20)30262-2. Erratum in: Lancet. 2020 May
30;395(10238):1694. PMID: 32305093; PMCID: PMC8151619.
5 Hwang S, et al. P632: COMPARISON OF TREATMENT-EMERGENT ADVERSE
EVENTS OF ACALABRUTINIB AND ZANUBRUTINIB IN CLINICAL TRIALS IN
B-CELL MALIGNANCIES: A SYSTEMATIC REVIEW AND META-ANALYSIS.
Hemasphere. 2023 Aug 8;7(Suppl ):e47546cf. doi:
10.1097/01.HS9.0000969432.47546.cf. PMCID: PMC10428881.
6 J. R. Brown, et. Al. Extended Follow-up of ALPINE Randomized
Phase 3 Study Confirms Sustained Superior Progression-Free Survival
of Zanubrutinib Versus Ibrutinib for Treatment of
Relapsed/Refractory Chronic Lymphocytic Leukemia and Small
Lymphocytic Lymphoma (R/R CLL/SLL). Blood 2023; 142 (Supplement 1):
202. doi: https://doi.org/10.1182/blood-2023-174289.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240229874068/en/
Investor: Liza Heapes +1 857-302-5663 ir@beigene.com
Media: Kyle Blankenship +1 667-351-5176
BeiGene (NASDAQ:BGNE)
Gráfica de Acción Histórica
De Abr 2024 a May 2024
BeiGene (NASDAQ:BGNE)
Gráfica de Acción Histórica
De May 2023 a May 2024