THOUSAND OAKS, Calif.,
July 7, 2021 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that the U.S. Food and Drug
Administration (FDA) has accepted a Biologics License Application
(BLA) and granted Priority Review for tezepelumab in the treatment
of asthma. Tezepelumab is being developed by Amgen in collaboration
with AstraZeneca.
The FDA grants Priority Review to applications for medicines
that offer significant advantages over available options by
demonstrating safety or efficacy improvements, preventing serious
conditions or enhancing patient compliance.1 The
Prescription Drug User Fee Act goal date for a decision by the FDA
is during the first quarter of 2022.
Despite recent advances in severe asthma, many patients may not
qualify for or respond well to current biologic
medicines.2-5 Patients with severe, uncontrolled asthma
experience frequent exacerbations, significant limitations on lung
function and a reduced quality of life.2,6,7
"Severe asthma is a challenging, complex disease for physicians
and millions of patients and has a high unmet medical need," said
David M. Reese, M.D., executive vice
president of Research and Development at Amgen. "We are proud to
advance an innovative, first-in-class monoclonal antibody that
targets the top of the inflammatory cascade and represents a
potentially transformative treatment option for a broad population
of patients with severe asthma. We look forward to bringing
tezepelumab to patients as quickly as possible."
The BLA was based on results from the PATHFINDER clinical trial
program, including results from the pivotal NAVIGATOR Phase 3 trial
in which tezepelumab demonstrated superiority across every primary
and key secondary endpoint compared to placebo in a broad
population of patients with uncontrolled asthma while receiving
treatment with medium- or high-dose inhaled corticosteroids (ICS)
plus at least one additional controller medication with or without
oral corticosteroids (OCS).8 There were no clinically
meaningful differences in safety results between the tezepelumab
and placebo groups in the NAVIGATOR trial.8 The most
frequently reported adverse events with tezepelumab were
nasopharyngitis, upper respiratory tract infection and
headache.8
Results from the NAVIGATOR Phase 3 trial were published in
the New England Journal of Medicine in
May 2021.
Tezepelumab was granted an FDA Breakthrough Therapy
Designation for patients with severe asthma without an
eosinophilic phenotype in September
2018.
About Severe Asthma
Globally, there are approximately 2.5 million patients with
severe asthma who are uncontrolled or biologic eligible, with
approximately 1 million in the U.S. Many patients with
severe asthma have an inadequate response to currently available
biologics and oral corticosteroids and thus fail to achieve asthma
control.2,6,9 Uncontrolled asthma occurs when
symptoms persist despite treatment. Severe, uncontrolled asthma is
debilitating with patients experiencing frequent exacerbations,
significant limitations on lung function and a reduced quality of
life.2,6,9 Patients with severe uncontrolled asthma
have twice the risk of asthma-related
hospitalizations.10,11 There is also a significant
socio-economic burden, with these severe, uncontrolled asthma
patients accounting for 50% of asthma-related
costs.12
Multiple inflammatory pathways are involved in the pathogenesis
of asthma.13-15 Eosinophilic asthma, and more
broadly, T2 inflammation-driven asthma, accounts for about
two-thirds of patients with severe asthma.15 These
patients are typically characterized as having elevated levels of
inflammatory biomarkers, including blood eosinophils, serum IgE and
fractional exhaled nitric oxide
(FeNO).16,17 However, many patients do not fit the
criteria for eosinophilic or allergic asthma, may have unclear or
multiple drivers of inflammation and may not qualify for or respond
well to a current biologic medicine.17
About the NAVIGATOR and the PATHFINDER Clinical Trial
Program
Building on the Phase 2b PATHWAY trial, the Phase 3 PATHFINDER program
included two trials, NAVIGATOR8,18 and
SOURCE.19,20 The program includes additional
planned mechanistic and long-term safety trials.21
NAVIGATOR is a Phase 3, randomized, double-blinded,
placebo-controlled trial in 1,061 adults (18–80 years old) and
adolescents (12–17 years old) with severe, uncontrolled asthma, who
were receiving treatment with medium- or high-dose inhaled
corticosteroids (ICS) plus at least one additional controller
medication with or without OCS. NAVIGATOR met the primary endpoint
with tezepelumab added to standard of care (SoC) demonstrating a
statistically significant and clinically meaningful reduction in
the annualized asthma exacerbation rate (AAER) over 52 weeks in the
overall patient population, compared to placebo added to SoC. The
trial also met the primary endpoint in the subgroup of patients
with baseline eosinophil counts less than 300 cells per microliter,
with tezepelumab demonstrating a statistically significant and
clinically meaningful reduction in AAER in that patient population.
Similar reductions in AAER were observed in the subgroup of
patients with baseline eosinophil counts less than 150 cells
pstoper microliter.21,22
NAVIGATOR primary
endpoints8
|
Endpoint
|
Timepoint
|
Annual
Exacerbation Rate
|
Results
Tezepelumab added
to SoC vs placebo added to SoC
|
Tezepelumab
|
Placebo
|
AAER – overall
patient population
|
Over 52
weeks
|
0.93 (95% CI: 0.80,
1.07)
|
2.10 (95% CI: 1.84,
2.39)
|
56% reduction (95%
CI: 47, 63; p<0.001)
|
AAER – baseline
eosinophil counts < 300 cells/µL
|
Over 52
weeks
|
1.02 (95% CI: 0.84,
1.23)
|
1.73 (95% CI: 1.46,
2.05)
|
41% reduction (95%
CI: 25, 54; p<0.001)
|
NAVIGATOR is the first Phase 3 trial to show benefit in severe
asthma irrespective of eosinophils by targeting the thymic stromal
lymphopoietin (TSLP). The U.S. Food and Drug
Administration Breakthrough Therapy Designation was granted to
tezepelumab in September 2018 for patients with severe
asthma, without an eosinophilic phenotype.
SOURCE is a Phase 3 multicenter, randomized, double-blinded,
parallel-group, placebo-controlled trial for 48 weeks in adult
patients with severe asthma who require continuous treatment with
ICS plus long-acting beta2-agonists (LABA), and chronic treatment
with maintenance OCS therapy. In the trial, patients were
randomized to receive tezepelumab 210 mg every four weeks or
placebo as add-on therapy, with patients maintained on their
currently prescribed ICS plus LABA, with or without other asthma
controller therapy.
Patients who participated in the NAVIGATOR and SOURCE trials
were eligible to continue in DESTINATION, a Phase 3 extension trial
assessing long-term safety and efficacy.23
About Tezepelumab
Tezepelumab is being developed by
AstraZeneca in collaboration with Amgen (see AstraZeneca and Amgen
collaboration below) as an investigational, potential
first-in-class human monoclonal antibody that works on the primary
source of inflammation: the airway epithelium, which is the first
point of contact for viruses, allergens, pollutants and other
environmental insults. Specifically, tezepelumab targets and blocks
thymic stromal lymphopoietin (TSLP), a key epithelial cytokine that
sits at the top of multiple inflammatory cascades and initiates an
overreactive immune response to allergic, eosinophilic and other
types of airway inflammation associated with severe
asthma.24,25
TSLP is released in response to multiple triggers associated
with asthma exacerbations, including allergens, viruses and other
airborne particles.24,25 Expression of TSLP is increased
in the airways of patients with asthma and has been correlated with
disease severity.24,26 Blocking TSLP may prevent the
release of pro-inflammatory cytokines by immune cells, resulting in
the prevention of asthma exacerbations and improved asthma
control.24,26 By working at the top of the cascade,
tezepelumab helps stop inflammation at the source and has the
potential to treat a broad population of severe asthma
patients.24,26
About the Amgen and AstraZeneca Collaboration
In
2020, Amgen and AstraZeneca updated the 2012 collaboration
agreement for tezepelumab. Both companies will continue to share
costs and profits equally after payment by AstraZeneca of a
mid-single-digit royalty to Amgen. AstraZeneca continues to lead
development and Amgen continues to lead manufacturing. All aspects
of the collaboration are under the oversight of joint governing
bodies. Under the amended agreement in North America, Amgen and AstraZeneca will
jointly commercialize tezepelumab; Amgen will record sales in the
U.S. and AstraZeneca will record sales in Canada. Outside the U.S., Amgen will
record sales as collaboration revenue.
Amgen Inflammation
Amgen brings therapies to millions
of people with inflammatory diseases, with a focus on serving unmet
patient needs. For those with debilitating moderate to severe
rheumatoid arthritis, psoriatic arthritis, moderate to severe
plaque psoriasis, ankylosing spondylitis, asthma, and other chronic
conditions, the suffering and needs are severe. Complex diseases of
inflammation have defied simple solutions, and the breadth of
inflammatory disease and the burden patients bear is not well
understood.
For more than two decades, Amgen has been committed to
advancing the science and the understanding around inflammation to
address the unmet patient needs that exist and expanding our
portfolio. We lead with science through discovery research that is
disease-agnostic and biology-first, modality-second. In doing so,
we have introduced and evolved novel therapies that have changed
the lives of patients.
Our commitment to patients is reflected not only in where we
have succeeded, but in where we have failed and opened new doors.
Throughout, we have remained dedicated to the principle of leading
with science, pursuing where pathways and promising discoveries in
inflammation take us, and not relenting until innovative solutions
for patients are found. It's a commitment that extends beyond
introducing novel therapies. We are focused on improving the entire
patient journey.
About Amgen
Amgen is committed to
unlocking the potential of biology for patients suffering from
serious illnesses by discovering, developing, manufacturing and
delivering innovative human therapeutics. This approach begins by
using tools like advanced human genetics to unravel the
complexities of disease and understand the fundamentals of human
biology.
Amgen focuses on areas of high unmet medical need and leverages
its expertise to strive for solutions that improve health outcomes
and dramatically improve people's lives. A biotechnology pioneer
since 1980, Amgen has grown to be one of the
world's leading independent biotechnology companies, has
reached millions of patients around the world and is developing a
pipeline of medicines with breakaway potential.
For more information, visit www.amgen.com and follow
us on www.twitter.com/amgen.
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collaborations, with any other company (including BeiGene, Ltd. or
any collaboration to manufacture therapeutic antibodies against
COVID-19), the performance of Otezla® (apremilast) (including
anticipated Otezla sales growth and the timing of non-GAAP EPS
accretion), or the Five Prime Therapeutics, Inc. acquisition, as
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