Submission based on data from Phase
2b HERIZON-BTC-01 trial, which met
its primary endpoint in patients receiving zanidatamab for
previously treated HER2-positive biliary tract cancer
(BTC)
Confirmatory Phase 3 trial in first-line (1L)
BTC open for enrollment at multiple global sites
DUBLIN, April 2,
2024 /PRNewswire/ -- Jazz Pharmaceuticals
plc (Nasdaq: JAZZ) today announced that the company has
completed the rolling submission of a Biologics License Application
(BLA) to the U.S. Food and Drug Administration (FDA) seeking
accelerated approval for the HER2-targeted bispecific antibody
zanidatamab as a treatment for previously-treated, unresectable,
locally advanced, or metastatic HER2-positive biliary tract
cancer (BTC). If approved, zanidatamab would be the first
HER2-targeted treatment specifically approved for BTC in the
U.S.
"This important milestone brings us one step closer to
delivering zanidatamab, a targeted treatment option, to patients
living with HER2-positive BTC, a type of cancer that is associated
with a five-year overall survival rate of less than 5%," said
Rob Iannone, M.D., M.S.C.E.,
executive vice president, global head of research and development
of Jazz Pharmaceuticals. "Zanidatamab is a biparatopic
HER2-targeted bispecific antibody that simultaneously binds two
non-overlapping epitopes of HER2 resulting in multiple mechanisms
of action. Second-line (2L) BTC represents the first of multiple
indications we are evaluating and we are excited about
zanidatamab's potential as a new option for multiple
HER2-expressing cancers, with ongoing Phase 3 trials in 1L BTC, 1L
gastroesophageal adenocarcinoma (GEA), and previously treated
breast cancer."
The BLA includes data from the Phase 2b HERIZON-BTC-01 trial of zanidatamab in
previously treated HER2-positive BTC. The primary endpoint was
confirmed objective response rate (cORR) by independent central
review (ICR) in Cohort 1. Data as of Oct.
10, 2022, from the 80 HER2-positive BTC patients enrolled in
Cohort 1 of the trial demonstrated a cORR of 41.3% [95% confidence
interval (CI): 30.4, 52.8] with a Kaplan
Meier (KM) estimated median duration of response (DOR) of
12.9 months [95% CI: 6.0-not estimable] by ICR. Historical response
rates for 2L standard-of-care chemotherapy in patients with BTC are
reported to be 5 to 15%1,2. The KM estimated median
progression-free survival (PFS) was 5.5 months [95% CI: 3.7,
7.2] with a range of 0.3 to 18.5 months.
Zanidatamab demonstrated a manageable and tolerable safety
profile, with only two patients (2.3%) in HERIZON-BTC-01
experiencing adverse events (AEs) leading to treatment
discontinuation. There were no Grade 4 AEs, and no deaths were
considered treatment-related. The most common AEs were diarrhea and
infusion-related reactions, which were predominately low-grade,
reversible and manageable prophylactically with routine supportive
care.
These data were featured as an oral presentation at the
American Society of Clinical Oncology (ASCO) Annual Meeting
2023, published in The Lancet Oncology, and
included in the 2023 Best of ASCO® program.
Quality-of-life data from this trial were also presented at the
European Society for Medical Oncology (ESMO) Congress 2023 and at
the 2024 ASCO Gastrointestinal Cancers Symposium.
The HERIZON-BTC-302 Phase 3 trial (NCT06282575)
of zanidatamab in 1L advanced or metastatic HER2-positive BTC
was recently initiated and is open for enrollment. The global,
open-label, randomized trial will evaluate the efficacy and safety
of zanidatamab in combination with standard-of-care therapy against
standard-of-care therapy alone. The primary objective of the study
is to compare the efficacy of zanidatamab and chemotherapy
(cisplatin plus gemcitabine) with or without the addition of a
programmed death protein 1/ligand 1 (PD-1/L-1) inhibitor versus
chemotherapy with or without a PD-1/L1 inhibitor in patients.
HERIZON-BTC-302 is proposed as the confirmatory trial for
zanidatamab in BTC.
About Zanidatamab
Zanidatamab is an investigational bispecific antibody that can
simultaneously bind two non-overlapping epitopes of HER2, known as
biparatopic binding. This unique design and increased binding
results in multiple mechanisms of action, including dual HER2
signal blockade, removal of HER2 protein from the cell surface, and
immune-mediated cytotoxicity leading to encouraging antitumor
activity in patients. Zanidatamab is being developed in
multiple clinical trials as a targeted treatment option for
patients with solid tumors that express HER2. Zanidatamab is
being developed by Jazz and BeiGene, Ltd. (BeiGene) under
license agreements from Zymeworks, which first developed the
molecule.
The U.S. Food and Drug Administration (FDA) has
granted Breakthrough Therapy designation for zanidatamab
development in patients with previously treated HER2 gene-amplified
biliary tract cancers (BTC), and two Fast Track designations for
zanidatamab: one as a single agent for refractory BTC and one in
combination with standard of care chemotherapy for 1L
gastroesophageal adenocarcinoma (GEA). Additionally,
zanidatamab has received Orphan Drug designations from FDA for the
treatment of BTC and GEA, as well as Orphan Drug designation from
the European Medicines Agency for the treatment of BTC
and gastric cancer. Zanidatamab was also granted Breakthrough
Therapy designation from the Center for Drug
Evaluation (CDE) in China.
About Biliary Tract Cancer
Biliary tract cancer (BTC), including gallbladder cancer and
intrahepatic and extrahepatic cholangiocarcinoma, account for
<1% of all adult cancers and are often associated with a poor
prognosis3,4. The human epidermal growth factor receptor
2 (HER2) is a well-validated target for antitumor therapy in other
cancers. Across the U.S., Europe, and Japan, approximately 12,000 people are
diagnosed with BTC annually5,6,7,8 and most
patients (> 65%) are diagnosed with tumors that cannot be
removed surgically.
About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc
(Nasdaq: JAZZ) is a global biopharma company whose purpose is to
innovate to transform the lives of patients and their families. We
are dedicated to developing life-changing medicines for people with
serious diseases—often with limited or no therapeutic options. We
have a diverse portfolio of marketed medicines, including leading
therapies for sleep disorders and epilepsy, and a growing portfolio
of cancer treatments. Our patient-focused and science-driven
approach powers pioneering research and development advancements
across our robust pipeline of innovative therapeutics in oncology
and neuroscience. Jazz is headquartered in Dublin, Ireland with research and development
laboratories, manufacturing facilities and employees in multiple
countries committed to serving patients worldwide. Please visit
www.jazzpharmaceuticals.com for more information.
Jazz Pharmaceuticals plc Caution Concerning
Forward-Looking Statements
This press release contains
forward-looking statements, including, but not limited to,
statements related to our goal of bringing to market the first
HER2-targeted treatment specifically approved for BTC, leading the
development of a HER2-targeted therapy with a unique bispecific
antibody with potential to treat multiple HER2-expressing cancers
and other statements that are not historical facts. These
forward-looking statements are based on Jazz Pharmaceuticals'
current plans, objectives, estimates, expectations and intentions
and inherently involve significant risks and uncertainties. Actual
results and the timing of events could differ materially from those
anticipated in such forward-looking statements as a result of these
risks and uncertainties, which include, without limitation, risks
and uncertainties associated with pharmaceutical product
development, and other risks and uncertainties affecting Jazz
Pharmaceuticals and its development programs, including those
described from time to time under the caption "Risk Factors" and
elsewhere in Jazz Pharmaceuticals plc's Securities and Exchange
Commission filings and reports (Commission File No. 001-33500),
including Jazz Pharmaceuticals' Annual Report on Form 10-K for the
year ended December 31, 2023, and
future filings and reports by Jazz Pharmaceuticals. Other risks and
uncertainties of which Jazz Pharmaceuticals is not currently aware
may also affect Jazz Pharmaceuticals' forward-looking statements
and may cause actual results and the timing of events to differ
materially from those anticipated. The forward-looking statements
herein are made only as of the date hereof or as of the dates
indicated in the forward-looking statements, even if they are
subsequently made available by Jazz Pharmaceuticals on its website
or otherwise. Jazz Pharmaceuticals undertakes no obligation to
update or supplement any forward-looking statements to reflect
actual results, new information, future events, changes in its
expectations or other circumstances that exist after the date as of
which the forward-looking statements were made.
Contacts:
Jazz Media Contact:
Kristin
Bhavnani
Head of Global Strategic Brand Engagement
Jazz Pharmaceuticals plc
CorporateAffairsMediaInfo@jazzpharma.com
Ireland +353 1 637 2141
U.S. +1 215 867 4948
Jazz Investor Contact:
Andrea
N. Flynn, Ph.D.
Vice President, Head, Investor Relations
Jazz Pharmaceuticals plc
investorinfo@jazzpharma.com
Ireland +353 1 634
3211
U.S. +1 650 496 2717
References:
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|
1
Lamarca A, et al. Second-line FOLFOX chemotherapy versus active
symptom control for advanced biliary tract cancer ABC-06): a phase
3, open-label, randomised, controlled trial. Lancet Oncol
2021;22:690–701
|
2 Yoo
C, et al. Liposomal irinotecan plus fluorouracil and leucovorin
versus fluorouracil and leucovorin for metastatic biliary tract
cancer after progression on gemcitabine plus cisplatin (NIFTY): a
multicentre, open-label, randomised, phase 2b study. Lancet Oncol
2021;22:1560–72
|
3
Valle JW, et al. Lancet 2021; 397:428-44
|
4
Siegel RL, et al. CA Cancer J Clin 2022; 72;7-33
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5 BTC
overall diagnosed patients as per SEER 22;
|
6
Assumes anatomic subsites intrahepatic CCA, extrahepatic CCA,
gallbladder cancer, and BTC unspecified;
|
7
Assumes HER2 positivity rates per anatomical subsite from: Galdy,
S., Lamarca, A., McNamara, M.G. et al. Cancer Metastasis Rev 36,
141–157 (2017), Nobuyoshi Hiraoka, et al. Human Pathology, Volume
105, 2020, Pages 9-19
|
8
Major markets: U.K, France, Germany, Spain, Italy. Note: HER2+ BTC
patients in Jazz-controlled commercial territories, which includes
Japan, and excludes other certain Asia Pacific countries licensed
to BeiGene, Ltd
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SOURCE Jazz Pharmaceuticals plc