THOUSAND OAKS, Calif.,
May 10, 2021 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today
announced its partner AstraZeneca (NASDAQ:AZN) submitted a
Biologics License Application (BLA) to the U.S. Food and Drug
Administration (FDA) for tezepelumab, a potential
first-in-class medicine in severe asthma. The submission is
supported by positive clinical trial results from the PATHFINDER
clinical program including the pivotal NAVIGATOR Phase 3 trial,
which demonstrated a statistically significant and clinically
meaningful reduction in the annualized asthma exacerbation rate
(AAER) in patients with severe, uncontrolled asthma compared to
placebo.1 Tezepelumab is the only biologic to
consistently and significantly reduce AAER in a broad population of
severe asthma patients irrespective of the baseline eosinophil
counts across Phase 2 and Phase 3 clinical trials.
"Severe asthma remains uncontrolled for many patients despite
current therapies for this complex and often debilitating
condition," said David M. Reese, M.D., executive vice
president of Research and Development at Amgen. "This
submission brings us one step closer to providing this potentially
transformative treatment option to a broad population of severe
asthma patients, across phenotypes and irrespective of
biomarkers."
Tezepelumab targets and blocks the action of an epithelial
cytokine called thymic stromal lymphopoietin (TSLP) which plays a
key role across the spectrum of asthma inflammation.2,3
In NAVIGATOR, tezepelumab demonstrated exacerbation rate reduction
irrespective of baseline eosinophil count and improvements in
lung function measurements, asthma control and health-related
quality of life compared to placebo.4 The most
frequently reported adverse events for tezepelumab were
nasopharyngitis, upper respiratory tract infection and headache.
These results support the FDA Breakthrough Therapy Designation
granted to tezepelumab in September
2018 for patients with severe asthma, without an
eosinophilic phenotype.
Data from the tezepelumab development program will be presented
at upcoming scientific meetings including the American Thoracic
Society 2021 International Conference later this month.
About Severe Asthma
Globally, there are approximately
2.5 million severe asthma patients who are uncontrolled or biologic
eligible, with approximately 1 million in the U.S. Many severe
asthma patients have an inadequate response to currently available
biologics and oral corticosteroids and thus fail to achieve asthma
control.5-7 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.5-7 Patients with severe uncontrolled
asthma have twice the risk of asthma-related
hospitalizations.8,9 There is also a significant
socio-economic burden, with these severe uncontrolled asthma
patients accounting for 50% of asthma-related
costs.10
Multiple inflammatory pathways are involved in the pathogenesis
of asthma.11,12,13 Eosinophilic asthma, and more
broadly, T2 inflammation-driven asthma, accounts for about
two-thirds of patients with severe asthma.13 These
patients are typically characterized as having elevated levels of
inflammatory biomarkers, including blood eosinophils, serum IgE and
fractional exhaled nitric oxide (FeNO).14,15 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.15
NAVIGATOR and the PATHFINDER Clinical Trial
Program
Building on the positive Phase 2b PATHWAY trial, the Phase 3 PATHFINDER program
included two trials, NAVIGATOR and SOURCE.16-19 The
program includes additional planned mechanistic and long-term
safety trials.
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 ICS plus at
least one additional controller medication with or without OCS.
NAVIGATOR met the primary endpoint with tezepelumab added to SoC
demonstrating a statistically significant and clinically meaningful
reduction in the 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 per
microliter.19
NAVIGATOR PRIMARY
ENDPOINTS4
|
Endpoint
|
Timepoint
|
Results
Tezepelumab added to
SoC vs placebo
added to SoC
|
AAER – overall
patient
population
|
Over 52
weeks
|
56% reduction* (95%
CI: 47, 63; p<0.001)
|
AAER –
overall
eosinophil counts
< 300
cells/µL
|
Over 52
weeks
|
41% reduction* (95%
CI: 25, 54; p<0.001)
|
CI: confidence
interval
|
|
|
NAVIGATOR is the first Phase 3 trial to show benefit in severe
asthma irrespective of eosinophils by targeting 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. 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. Tezepelumab is being developed
by AstraZeneca in collaboration with Amgen (see AstraZeneca and
Amgen collaboration below).
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.17 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.17
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.20
About Tezepelumab
Tezepelumab is 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.2,16,21
TSLP is released in response to multiple triggers associated
with asthma exacerbations, including allergens, viruses and other
airborne particles. 2,21 Expression of TSLP is
increased in the airways of patients with asthma and has been
correlated with disease severity.2,16 Blocking TSLP
may prevent the release of pro-inflammatory cytokines by immune
cells, resulting in the prevention of asthma exacerbations and
improved asthma control. 2,16 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.2,16
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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the outcome, benefits and synergies of collaborations, or potential
collaborations, with any other company (including BeiGene, Ltd. or
any collaboration to manufacture therapeutic antibodies against
COVID-19), the performance of Otezla® (apremilast)
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non-GAAP EPS accretion), or the Five Prime Therapeutics, Inc.
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