THOUSAND OAKS, Calif.,
Nov. 9, 2020 /PRNewswire/ -- Amgen (NASDAQ:AMGN) and
AstraZeneca today announced positive topline results from the Phase
3 NAVIGATOR trial in which the investigational medicine tezepelumab
demonstrated a statistically significant reduction in exacerbations
compared to placebo in patients with severe asthma.
The NAVIGATOR trial met the primary endpoint with tezepelumab
added to standard of care (SoC) demonstrating a statistically
significant and clinically meaningful reduction compared to placebo
plus SoC in the annualized asthma exacerbation rate (AAER) over 52
weeks in the overall patient population. SoC was medium- or
high-dose inhaled corticosteroids (ICS) plus at least one
additional controller medication with or without oral
corticosteroids (OCS).
In the subgroup of patients with baseline eosinophil counts less
than 300 cells per microliter, the trial met the primary endpoint
with tezepelumab demonstrating a statistically significant and
clinically meaningful reduction in AAER. Similar reductions
in AAER were observed in the subgroup of patients with baseline
eosinophil counts less than 150 cells per microliter.
The significant exacerbation rate reductions demonstrated with
tezepelumab in patients with baseline eosinophil counts less than
300 cells per microliter support the U.S. Food and Drug
Administration Breakthrough Therapy Designation granted to
tezepelumab in Sept. 2018 for
patients with severe asthma, without an eosinophilic phenotype.
Tezepelumab was very well tolerated in patients with severe
asthma. Preliminary analyses show no clinically meaningful
differences in safety results between the tezepelumab and placebo
groups. Results from the NAVIGATOR trial will be presented at
an upcoming medical meeting.
Tezepelumab is a potential first-in-class medicine that blocks
the action of thymic stromal lymphopoietin (TSLP), an epithelial
cytokine that plays a key role across the spectrum of asthma
inflammation.1,2 NAVIGATOR is the first Phase 3
trial to show benefit in severe asthma by targeting TSLP.
"We are absolutely thrilled with the topline results of the
NAVIGATOR study in this broad population of patients with severe
asthma, regardless of eosinophil count," said David M. Reese, M.D., executive vice president
of Research and Development at Amgen. "Tezepelumab represents a
potential new class of biologics that could enable us to treat
severe asthma at the top of the inflammatory cascade, addressing a
high unmet need among the millions of patients living with severe
asthma throughout the world. Tezepelumab has the potential to
revolutionize care with efficacy demonstrated even in patients with
a low eosinophil count."
Professor Andrew Menzies-Gow,
director of the Lung Division, Royal Brompton Hospital,
London, UK, and principal
investigator of the NAVIGATOR trial said: "Due to the complex
nature of severe asthma, many patients continue to face
debilitating asthma despite receiving standard of care inhaled
medicines and currently approved biologics. Today's ground-breaking
results show that tezepelumab has the potential to transform care
for a broad population of severe asthma patients who are
underserved today, including those without an eosinophilic
phenotype."
Amgen and AstraZeneca Collaboration
Earlier 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.
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 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.1,2,3
TSLP is released in response to multiple triggers associated
with asthma exacerbations, including allergens, viruses and other
airborne particles.1,2 Expression of TSLP is increased
in the airways of patients with asthma and has been correlated with
disease severity.2,3 Blocking TSLP may prevent the
release of pro-inflammatory cytokines by immune cells, resulting in
the prevention of asthma exacerbations and improved asthma
control.2,3 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.2,3
NAVIGATOR and the PATHFINDER clinical trial
program
Building on the Phase 2b PATHWAY trial, the Phase 3 PATHFINDER program
included two trials, NAVIGATOR and SOURCE.4,5 The
program includes additional planned mechanistic and long-term
safety trials.
NAVIGATOR is a Phase 3, randomized, double-blinded,
placebo-controlled trial in 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. The
trial population included approximately equal proportions of
patients with high (≥ 300 cells/µL) and low (< 300 cells/µL)
blood eosinophil counts. The trial comprised a five to six week
screening period, a 52-week treatment period and a 12-week
post-treatment follow-up period. All patients received their
prescribed controller medications without change throughout the
trial.4
The primary efficacy endpoint was the annualized asthma
exacerbation rate during the 52-week treatment period. Key
secondary endpoints included the effect of tezepelumab on lung
function, asthma control and health-related quality of
life.4
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. The primary endpoint is the
categorized % reduction from baseline in the daily OCS dose while
not losing asthma control.5
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.5
About Severe Asthma
Asthma is a complex and
heterogeneous disease affecting an estimated 339 million people
worldwide.6,7 Approximately 10% of asthma patients
have severe asthma.6,7 Yet, many severe asthma patients
have an inadequate response to currently available biologics and
oral corticosteroids and thus fail to achieve asthma
control.6-8 Severe, uncontrolled asthma is debilitating
with patients experiencing frequent exacerbations, significant
limitations on lung function and a reduced quality of
life.6-8 Patients with severe asthma account for
twice as many asthma-related
hospitalizations.9,10 There is also a significant
socio-economic burden, with these patients accounting for 50% of
asthma-related costs.11
Multiple inflammatory pathways are involved in the pathogenesis
of asthma.12,13,14 Eosinophilic asthma, and more
broadly, T2 inflammation-driven asthma, accounts for about
two-thirds of patients with severe asthma.14 These
patients are typically characterized as having elevated levels of
inflammatory biomarkers, including blood eosinophils, serum IgE and
fractional exhaled nitric oxide
(FeNO).4,15 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
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.
Amgen Forward-Looking Statements
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contains forward-looking statements that are based on the current
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collaborations, with any other company, including BeiGene, Ltd. or
any collaboration or potential collaboration in pursuit of
therapeutic antibodies against COVID-19 (including statements
regarding such collaboration's, or Amgen's, ability to discover and
develop fully-human neutralizing antibodies targeting SARS-CoV-2 or
antibodies against targets other than the SARS-CoV-2 receptor
binding domain, and/or to produce any such antibodies to
potentially prevent or treat COVID-19), or the Otezla® (apremilast)
acquisition (including anticipated Otezla sales growth and the
timing of non-GAAP EPS accretion), as well as estimates of
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CONTACT: Amgen, Thousand Oaks
Megan Fox, 805-447-1423 (media)
Trish Rowland, 805-447-5631
(media)
Arvind Sood, 805-447-1060
(investors)
1 Varricchi G, Pecoraro A, Marone G, et
al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory
Disorders, and Cancer. Front Immunol. 2018; 9: 1595.
2 Corren J, Parnes JR, Wang L, et al.
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correction appears in N Engl J Med. 2019 May
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3 Roseti S, Corren J, Parnes JR, et al.
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Adults With Oral Corticosteroid Dependent Asthma (SOURCE)
[Online]. Available
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5 Clinicaltrials.gov. Extension Study to Evaluate the
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[Last accessed: September 2020].
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7 Wenzel S. Severe Asthma in Adults. Am J
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8 Chung KF, Wenzel SE, Brozek JL, et al.
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9 Price D, Fletcher M, van der Molen T. Asthma
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10 World Allergy Organization (WAO). The
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[Last accessed: September 2020]
11 Busse WW. Biological Treatments for Severe
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12 Godar M, Blanchetot C, de Haard H, et
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13 Rabe KF, Busse W, Pavord I, Castro M. Raising
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