Merus Announces FDA Approval of BIZENGRI® (zenocutuzumab-zbco) for
NRG1+ Pancreatic Adenocarcinoma and NRG1+ Non–Small Cell Lung
Cancer (NSCLC) Based on Safety and Efficacy Data From the eNRGy
Study
- BIZENGRI® is the first and only therapy approved by
the FDA specifically for pancreatic adenocarcinoma and NSCLC that
harbor NRG1 gene fusions and are advanced unresectable or
metastatic1
- Merus and Partner Therapeutics announced a license agreement
for U.S. commercialization
UTRECHT, The Netherlands and CAMBRIDGE, Mass., Dec. 04, 2024
(GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq: MRUS) [Merus, the Company,
we, or our], a clinical-stage oncology company developing
innovative, full-length, multispecific antibodies
(Biclonics® and Triclonics®), announced
today that the U.S. Food and Drug Administration (FDA) approved
BIZENGRI® (zenocutuzumab-zbco), the first and only
treatment indicated for adults with pancreatic adenocarcinoma or
non–small cell lung cancer (NSCLC) that are advanced unresectable
or metastatic and harbor a neuregulin 1 (NRG1) gene fusion
who have disease progression on or after prior systemic therapy.
These indications are approved under accelerated approval based on
overall response rate (ORR) and duration of response (DOR).
Continued approval for these indications may be contingent upon
verification and description of clinical benefit in a confirmatory
trial(s). BIZENGRI® has a Boxed WARNING for Embryo-Fetal
Toxicity and warnings for infusion-related reactions (IRRs),
hypersensitivity and anaphylactic reactions, interstitial lung
disease (ILD)/pneumonitis, and left ventricular
dysfunction.1 See Important Safety Information
below.
We believe this approval fills an important need for patients
with NRG1+ cancer who have not previously had treatment
options approved to specifically target this driver.
BIZENGRI® (zenocutuzumab-zbco) 20 mg/mL Injection for
Intravenous Use is expected to be available to patients in the
coming weeks.
“The FDA approval of BIZENGRI® marks an important
milestone for patients with pancreatic adenocarcinoma or NSCLC that
is advanced unresectable or metastatic and harbors the
NRG1 gene fusion. I have seen firsthand how treatment with
BIZENGRI® can deliver clinically meaningful outcomes for
patients,” said Alison Schram, MD, an attending medical oncologist
in the Early Drug Development Service at Memorial Sloan Kettering
Cancer Center and a principal investigator for the ongoing eNRGy
trial. “I am extraordinarily grateful for the patients and families
who participated in the trial.”
“BIZENGRI® is Merus’s first approved medicine
based on our highly innovative and
proprietary Biclonics® technology platform and
offers significant promise for patients with NRG1+
pancreatic adenocarcinoma and NRG1+ NSCLC,” said
Shannon Campbell, Chief Commercial Officer of Merus. “This approval
is a testament to both our technology and strong execution as we
continue to develop our multispecific platforms and pipeline,
including our lead asset petosemtamab.”
The approval of BIZENGRI® is based on data from the
eNRGy trial, a multicenter, open-label clinical trial that enrolled
patients with NRG1+ pancreatic adenocarcinoma or
NRG1+ NSCLC that is advanced unresectable or metastatic
and had disease progression on or after prior systemic therapy. In
patients with NRG1+ pancreatic adenocarcinoma (n=30),
BIZENGRI® demonstrated an ORR of 40% (95% CI, 23%-59%).
DOR in NRG1+ pancreatic adenocarcinoma ranged from 3.7
months to 16.6 months. In the same trial, patients with
NRG1+ NSCLC (n=64) who were treated with
BIZENGRI® demonstrated an ORR of 33% (95% CI, 22%-46%).
The median DOR in NRG1+ NSCLC was 7.4 months (95% CI,
4.0-16.6). Response rates were measured using the Response
Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by
blinded independent central review (BICR). In the pooled safety
population (N=175), the most common (≥10%) adverse reactions were
diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related
reactions (IRR), dyspnea, rash, constipation, vomiting, abdominal
pain, and edema. The most common Grade 3 or 4 laboratory
abnormalities (≥2%) were increased gamma-glutamyltransferase,
decreased hemoglobin, decreased sodium, decreased platelets,
increased aspartate aminotransferase, increased alanine
aminotransferase, increased alkaline phosphatase, decreased
magnesium, decreased phosphate, increased activated partial
thromboplastin time, and increased bilirubin.
“The Personalized Medicine Coalition applauds the approval of
BIZENGRI®, a new targeted therapy for NRG1+
pancreatic adenocarcinoma and NRG1+ NSCLC that are
advanced unresectable or metastatic,” said Edward Abrahams,
President of the Washington-based education and advocacy
organization. “In keeping with the growing number of personalized
medicines on the market today, BIZENGRI® offers the only
approved NRG1+ therapy for patients with these
difficult-to-treat cancers.”
The company plans to help appropriate patients gain access to
BIZENGRI® by providing resources and support based on
each patient's needs and situation. PTx Assist™ is available
to help guide patients through treatment, from providing
educational information to helping to understand insurance coverage
and identifying potential financial assistance options. For
more information, patients and providers can call 1-844-637-8777,
Monday through Friday, from 8:00 a.m. to 8:00 p.m. ET.
Please see full Prescribing Information, including Boxed
WARNING, at www.BIZENGRI.com/pi.
About BIZENGRI®
BIZENGRI® is a bispecific antibody that binds to the
extracellular domains of HER2 and HER3 expressed
on the surface of cells, including tumor cells, inhibiting
HER2:HER3 dimerization and preventing NRG1
binding to HER3. BIZENGRI® decreased cell
proliferation and signaling through the phosphoinositide
3-kinase-AKT-mammalian target of rapamycin pathway. In addition,
BIZENGRI® mediates antibody-dependent cellular
cytotoxicity. BIZENGRI® showed antitumor activity in
mouse models of NRG1+ lung and pancreatic
cancers.1
About the eNRGy Trial
The eNRGy trial (Clinicaltrials.gov NCT02912949) is a
multicenter, open-label clinical trial that includes patients with
advanced unresectable or metastatic NRG1+ pancreatic
adenocarcinoma or NRG1+ NSCLC who have disease progression
on or after prior systemic therapy. There were 30 patients in the
NRG1+ pancreatic adenocarcinoma group and 64 patients in
the NRG1+ NSCLC group. The main outcome measures were ORR
and DOR, as determined by BICR according to Response Evaluation
Criteria in Solid Tumors (RECIST) v1.1.1
In the NRG1+ pancreatic adenocarcinoma group, the
median age was 49 years (range, 21-72 years); 43% were female; 87%
were White, 7% were Asian, and 3.3% were Black or African American.
All patients had an Eastern Cooperative Oncology Group (ECOG)
performance status of 0 or 1, and all patients had metastatic
disease. Patients received a median of 2 prior systemic therapies
(range, 0-5); 97% had prior systemic therapy with prior
chemotherapy.1
In the NRG1+ NSCLC group, the median age was 64 years
(range, 32-86 years); 64% were female, 33% were White, 56% were
Asian, and 3.4% were Black or African American. ECOG performance
status was 0 or 1 in 97% of patients or 2 in 3% of patients, and
98% of patients had metastatic disease. Patients received a median
of 2 prior systemic therapies (range, 1-6).1
IMPORTANT SAFETY INFORMATION
BOXED WARNING: EMBRYO-FETAL TOXICITY
Embryo-Fetal Toxicity: Exposure to BIZENGRI®
during pregnancy can cause embryo-fetal harm. Advise patients of
this risk and the need for effective contraception.
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions/Hypersensitivity/Anaphylactic
Reactions
BIZENGRI® can cause serious and life-threatening
infusion-related reactions (IRRs), hypersensitivity and
anaphylactic reactions. Signs and symptoms of IRR may include
chills, nausea, fever, and cough.
In the eNRGy study, 13% of patients experienced IRRs, all were
Grade 1 or 2; 91% occurred during the first infusion.
Administer BIZENGRI® in a setting with emergency
resuscitation equipment and staff who are trained to monitor for
IRRs and to administer emergency medications. Monitor patients
closely for signs and symptoms of infusion reactions during
infusion and for at least 1 hour following completion of first
BIZENGRI® infusion and as clinically indicated.
Interrupt BIZENGRI® infusion in patients with ≤ Grade 3
IRRs and administer symptomatic treatment as needed. Resume
infusion at a reduced rate after resolution of symptoms.
Immediately stop the infusion and permanently discontinue
BIZENGRI® for Grade 4 or life-threatening IRR or
hypersensitivity/anaphylaxis reactions.
Interstitial Lung Disease/Pneumonitis
BIZENGRI® can cause serious and life-threatening
interstitial lung disease (ILD)/pneumonitis. In the eNRGy study,
ILD/pneumonitis occurred in 2 (1.1%) patients treated with
BIZENGRI®. Grade 2 ILD/pneumonitis (Grade 2) resulting
in permanent discontinuation of BIZENGRI® occurred in 1
(0.6%) patient. Monitor for new or worsening pulmonary symptoms
indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever).
Immediately withhold BIZENGRI® in patients with
suspected ILD/pneumonitis and administer corticosteroids as
clinically indicated. Permanently discontinue BIZENGRI®
if ILD/pneumonitis ≥ Grade 2 is confirmed.
Left Ventricular Dysfunction
BIZENGRI® can cause left ventricular dysfunction.
Left ventricular ejection fraction (LVEF) decrease has been
observed with anti-HER2 therapies, including BIZENGRI®.
Treatment with BIZENGRI® has not been studied in
patients with a history of clinically significant cardiac disease
or LVEF less than 50% prior to initiation of treatment.
In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10 - 19%
drop from baseline) occurred in 2% of evaluable patients. Cardiac
failure without LVEF decrease occurred in 1.7% of patients,
including 1 (0.6%) fatal event.
Before initiating BIZENGRI®, evaluate LVEF and
monitor at regular intervals during treatment as clinically
indicated. For LVEF of less than 45% or less than 50% with absolute
decrease from baseline of 10% or greater which is confirmed, or in
patients with symptomatic congestive heart failure (CHF),
permanently discontinue BIZENGRI®.
Embryo-Fetal Toxicity
Based on its mechanism of action, BIZENGRI® can cause
fetal harm when administered to a pregnant woman. No animal
reproduction studies were conducted with BIZENGRI®. In
postmarketing reports, use of a HER2-directed antibody during
pregnancy resulted in cases of oligohydramnios manifesting as fatal
pulmonary hypoplasia, skeletal abnormalities, and neonatal death.
In animal models, studies have demonstrated that inhibition of HER2
and/or HER3 results in impaired embryo-fetal development, including
effects on cardiac, vascular and neuronal development, and
embryolethality. Advise patients of the potential risk to a fetus.
Verify the pregnancy status of females of reproductive potential
prior to the initiation of BIZENGRI®. Advise females of
reproductive potential to use effective contraception during
treatment with BIZENGRI® and for 2 months after the last
dose.
ADVERSE REACTIONS
NRG1 Gene Fusion Positive
Unresectable or Metastatic Pancreatic Adenocarcinoma
Serious adverse reactions occurred in 23% of patients with NRG1
Gene Fusion Positive Pancreatic Adenocarcinoma who received
BIZENGRI®.
There were 2 fatal adverse reactions, one due to COVID-19 and
one due to respiratory failure.
In patients with NRG1 Gene Fusion Positive Pancreatic
Adenocarcinoma who received BIZENGRI® the most common
(≥20%) adverse reactions, including laboratory abnormalities, were
increased alanine aminotransferase (51%), diarrhea (36%), increased
aspartate aminotransferase (31%), increased bilirubin (31%),
decreased phosphate (31%), increased alkaline phosphatase (28%),
decreased sodium (28%) musculoskeletal pain (28%), decreased
albumin (26%), decreased potassium (26%), decreased platelets
(26%), decreased magnesium (24%), increased gamma-glutamyl
transpeptidase (23%), decreased hemoglobin (23%), vomiting (23%),
nausea (23%), decreased leukocytes (21%), and fatigue (21%).
NRG1 Gene Fusion Positive
Unresectable or Metastatic NSCLC
Serious adverse reactions occurred in 25% of patients with NRG1
Gene Fusion Positive NSCLC who received BIZENGRI®.
Serious adverse reactions in ≥ 2% of patients included pneumonia
(n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions
occurred in 3 (3%) patients and included respiratory failure (n=2),
and cardiac failure (n=1). Permanent discontinuation of
BIZENGRI® due to an adverse reaction occurred in 3% of
patients. Adverse reactions resulting in permanent discontinuation
of BIZENGRI® included dyspnea, pneumonitis and sepsis
(n=1 each).
In patients with NRG1 Gene Fusion Positive NSCLC who received
BIZENGRI®, the most common (>20%) Adverse Reactions,
including laboratory abnormalities, were decreased hemoglobin
(35%), increased alanine aminotransferase (30%), decreased
magnesium (28%), increased alkaline phosphatase (27%), decreased
phosphate (26%) diarrhea (25%), musculoskeletal pain (23%),
increased gamma-glutamyl transpeptidase (23%), increased aspartate
aminotransferase (22%), and decreased potassium (21%).
Please see full Prescribing Information, including Boxed
WARNING, at BIZENGRI.com/pi.
About Merus N.V.
Merus is a clinical stage oncology company developing innovative
full-length human bispecific and trispecific antibody therapeutics,
referred to as Multiclonics®. Multiclonics®
are manufactured using industry standard processes and have been
observed in preclinical and clinical studies to have several of the
same features of conventional human monoclonal antibodies, such as
long half-life and low immunogenicity. For additional information,
please visit Merus’ website https://merus.nl and LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. All statements contained in this press release that do not
relate to matters of historical fact should be considered
forward-looking statements, including without limitation,
statements regarding product development and the potential benefits
and treatment impact of BIZENGRI® (zenocutuzumab-zbco);
our belief that this approval fills an important need for patients
with NRG1+ cancer who have not previously had treatment
options approved to specifically target this driver; the
expectation of BIZENGRI® to be available to patients in
the coming weeks; the promise BIZENGRI® holds for patients with
NRG1+ pancreatic adenocarcinoma and NSCLC; its implication
to our technology and execution as we continue to develop our
multispecific platforms and pipeline, including our lead asset
petosemtamab; and our expectation to provide patients with access
to BIZENGRI®, as well as offering helpful resources and
support based on each patient's needs and situation. The reader is
cautioned not to rely on these forward-looking statements. These
statements are based on current expectations of future events. If
underlying assumptions prove inaccurate or known or unknown risks
or uncertainties materialize, actual results could vary materially
from the expectations and projections of Merus. Risks and
uncertainties include, but are not limited to: challenges and
uncertainties inherent in product research and development,
including the uncertainty of clinical success and of obtaining
regulatory approvals; uncertainty of commercial success;
manufacturing difficulties and delays; competition, including
technological advances, new products and patents attained by
competitors; challenges to patents; product efficacy or safety
concerns resulting in product recalls or regulatory action; changes
in behavior and spending patterns of purchasers of health care
products and services; changes to applicable laws and regulations,
including global health care reforms; and trends toward health care
cost containment. These statements are neither promises nor
guarantees, but involve known and unknown risks, uncertainties, and
other important factors that may cause our actual results,
performance, or achievements to be materially different from any
future results, performance, or achievements expressed or implied
by the forward-looking statements, including, but not limited to,
the following: our need for additional funding, which may not be
available and which may require us to restrict our operations or
require us to relinquish rights to our technologies or antibody
candidates; potential issues associated with regulatory approval,
which would impact our ability to commercialize our product
candidates and affect our ability to generate revenue; the lengthy
and expensive process of clinical drug development, which has an
uncertain outcome; our reliance on third parties to conduct our
clinical trials, and the potential for those third parties to not
perform satisfactorily; impacts of the volatility in the global
economy, including global instability, including the ongoing
conflicts in Europe and the Middle East; we may not identify
suitable Biclonics® or bispecific antibody candidates
under our collaborations, or our collaborators may fail to perform
adequately under our collaborations; our reliance on third parties
to manufacture our product candidates, which may delay, prevent, or
impair our development and commercialization efforts; protection of
our proprietary technology; our patents may be found invalid,
unenforceable, circumvented by competitors, and our patent
applications may be found not to comply with the rules and
regulations of patentability; we may fail to prevail in potential
lawsuits for infringement of third-party intellectual property; and
our registered or unregistered trademarks or trade names may be
challenged, infringed, circumvented, or declared generic or
determined to be infringing on other marks. These and other
important factors discussed under the caption “Risk Factors” in our
Quarterly Report on Form 10-Q for the period ended September 30,
2024, filed with the Securities and Exchange Commission, or SEC, on
October 31, 2024, and our other reports filed with the SEC, could
cause actual results to differ materially from those indicated by
the forward-looking statements made in this press release. Any such
forward-looking statements represent management’s estimates as of
the date of this press release. While we may elect to update such
forward-looking statements at some point in the future, we disclaim
any obligation to do so, even if subsequent events cause our views
to change, except as required under applicable law. These
forward-looking statements should not be relied upon as
representing our views as of any date subsequent to the date of
this press release.
Multiclonics®, Biclonics®,
Triclonics®, and BIZENGRI® are registered
trademarks of Merus N.V.
Reference: 1. BIZENGRI. Prescribing
information. Merus N.V.; 2024.
©2024 Merus N.V. All rights reserved.
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