Late-breaking results from the Phase IIa
COURSE trial provide insight into TEZSPIRE’s impact on COPD
exacerbations in patients with a broad range of eosinophil
levels
The Phase IIa COURSE trial was a proof-of-concept study in
people with moderate to very severe chronic obstructive pulmonary
disease (COPD) with a broad range of blood eosinophil counts (BEC)
and irrespective of emphysema, chronic bronchitis or smoking
status.1 The primary results showed that treatment with AstraZeneca
and Amgen’s TEZSPIRE® (tezepelumab) led to a 17% numerical
reduction in the annual rate of moderate or severe COPD
exacerbations compared to placebo at week 52, which was not
statistically significant (90% CI (Confidence Interval): -6, 36], p
[1-sided]=0.1042).1 The results are being presented at the American
Thoracic Society (ATS) International Conference.
Importantly, in patients with BEC ≥150 cells/µL, tezepelumab led
to a nominally significant reduction of 37% in the rate of moderate
or severe exacerbations compared to placebo.1 Studies suggest that
approximately 65% of bio-eligible patients with COPD have a BEC
greater than or equal to 150 cells/μL.2 In patients with BEC ≥300
cells/µL tezepelumab led to a numerical reduction of 46% in the
rate of moderate or severe exacerbations.1 (Table 1.)
Dr Dave Singh, Professor of Respiratory Pharmacology at the
University of Manchester and lead investigator on the trial, said:
“I believe that biologics will play a critical role in the future
care of COPD and trials such as the tezepelumab COURSE trial are
central to understanding and shaping the treatment landscape. The
tezepelumab COURSE results are particularly important as they show
activity in COPD across a broad patient population including those
with baseline blood eosinophil counts greater than 150
cells/μL.”
Sharon Barr, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: “These proof-of-concept results from
the COURSE trial are encouraging as they signal the potential
efficacy of tezepelumab in a broad range of people with COPD
irrespective of emphysema, chronic bronchitis and smoking status.
As a result of these promising data, we are actively in Phase III
planning for tezepelumab in COPD.”
A subgroup analysis of the COURSE trial also showed treatment
with tezepelumab resulted in numerical improvements in lung
function as measured by forced expiratory volume (FEV1)
(improvement of 63mL and 146mL in BEC ≥150 and ≥300 cells/μL
respectively, compared to placebo) and in quality of life as
measured by the St. George’s Respiratory Questionnaire (SGRQ) score
(reduction of 4.2 points and 9.5 points in BEC ≥150 and ≥300
cells/μL respectively).1 The safety and tolerability profile for
tezepelumab was consistent with its approved severe asthma
indication; the most frequently reported (>10%) adverse events
for tezepelumab were worsening of COPD (12.1%) and incidents of
COVID-19 infections (14.5%) (this trial commenced in July 2019).1
(Table 2.)
COURSE Phase IIa analysis:
Table 1: Tezepelumab impact on COPD exacerbations versus
placebo over 52 weeks1
Reduction in exacerbations compared to
placebo
Annualized rate of
exacerbations
Moderate or severe
exacerbations
Overall population (n=333)
17% (90% CI: -6, 36)
1.75 in tezepelumab group versus 2.11 in
placebo group
BEC less than 150 cells/μL
(n=137)
-19% (95% CI: -90, 25)
2.04 in tezepelumab group versus 1.71 in
placebo group
BEC greater than or equal to 150
cells/μL (n=196)
37% (95% CI: 7, 57)
1.52 in tezepelumab group versus 2.40 in
placebo group
BEC greater than or equal to 300
cells/μL (n=56)
46% (95% CI: -15, 75)
1.20 in tezepelumab group versus 2.24 in
placebo group
Severe exacerbations
Overall population (n=333)
48% (95% CI: -11, 76)
0.13 in tezepelumab group versus 0.25 in
placebo group
Table 2: Tezepelumab impact on quality of life and lung
function versus placebo over 52 weeks1
Lung function as measured by
pre-bronchodilator forced expiratory volume (FEV1, µL)
Quality of life improvement as measured
by St. George’s Respiratory Questionnaire (SGRQ) score
Tezepelumab
(n)/LS Mean
Placebo
(n)/LS
Mean
LS mean
difference
(95% CI)
Tezepelumab
(n)/LS Mean
Placebo
(n)/LS
Mean
LS mean
difference
(95% CI)
BEC less than 150
cells/μL
73/-0.002
63/-0.053
0.051 (-0.012,0.114)
69/-1.91
60/-0.30
-1.62 (-6.69, 3.45)
BEC greater than or equal to
150 cells/μL
90/0.049
103/-0.014
0.063 (0.009, 0.116)
88/-7.08
96/-2.85
-4.23 (-8.51, 0.06)
BEC counts greater than or
equal to 300 cells/μL
24/0.160
31/0.013
0.146 (0.044, 0.248)
22/-10.22
27/-0.68
-9.53 (-18.11, -0.96)
INDICATIONS AND LIMITATIONS OF USE / ISI
TEZSPIRE® (tezepelumab)
CONTRAINDICATIONS
Known hypersensitivity to tezepelumab-ekko or excipients.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions were observed in the clinical trials
(eg, rash and allergic conjunctivitis) following the administration
of TEZSPIRE. Postmarketing cases of anaphylaxis have been reported.
These reactions can occur within hours of administration, but in
some instances have a delayed onset (ie, days). In the event of a
hypersensitivity reaction, consider the benefits and risks for the
individual patient to determine whether to continue or discontinue
treatment with TEZSPIRE.
Acute Asthma Symptoms or Deteriorating Disease
TEZSPIRE should not be used to treat acute asthma symptoms,
acute exacerbations, acute bronchospasm, or status asthmaticus.
Abrupt Reduction of Corticosteroid Dosage
Do not discontinue systemic or inhaled corticosteroids abruptly
upon initiation of therapy with TEZSPIRE. Reductions in
corticosteroid dose, if appropriate, should be gradual and
performed under the direct supervision of a physician. Reduction in
corticosteroid dose may be associated with systemic withdrawal
symptoms and/or unmask conditions previously suppressed by systemic
corticosteroid therapy.
Parasitic (Helminth) Infection
It is unknown if TEZSPIRE will influence a patient’s response
against helminth infections. Treat patients with pre-existing
helminth infections before initiating therapy with TEZSPIRE. If
patients become infected while receiving TEZSPIRE and do not
respond to anti-helminth treatment, discontinue TEZSPIRE until
infection resolves.
Live Attenuated Vaccines
The concomitant use of TEZSPIRE and live attenuated vaccines has
not been evaluated. The use of live attenuated vaccines should be
avoided in patients receiving TEZSPIRE.
ADVERSE REACTIONS
The most common adverse reactions (incidence ≥3%) are
pharyngitis, arthralgia, and back pain.
USE IN SPECIFIC POPULATIONS
There are no available data on TEZSPIRE use in pregnant women to
evaluate for any drug-associated risk of major birth defects,
miscarriage, or other adverse maternal or fetal outcomes. Placental
transfer of monoclonal antibodies such as tezepelumab-ekko is
greater during the third trimester of pregnancy; therefore,
potential effects on a fetus are likely to be greater during the
third trimester of pregnancy.
INDICATION
TEZSPIRE is indicated for the add-on maintenance treatment of
adult and pediatric patients aged 12 years and older with severe
asthma.
TEZSPIRE is not indicated for the relief of acute bronchospasm
or status asthmaticus.
Please see full Prescribing Information,
including Patient Information and Instructions
for Use.
You may report side effects related to AstraZeneca products.
Notes
COURSE Phase IIa trial
COURSE was a Phase IIa multicentre, randomized, double-blind,
placebo-controlled, parallel group trial designed to evaluate the
safety and efficacy of tezepelumab in adults with moderate to very
severe chronic obstructive pulmonary disease (COPD) receiving
triple inhaled maintenance therapy, and having had two or more
documented COPD exacerbations in the 12 months prior to Visit 1. A
total of 337 patients were randomized globally, with patients
stratified by region and prior number of exacerbations (two vs.
three or more). Patients received tezepelumab 420 mg, or placebo,
administered via subcutaneous injection at the trial site every
four weeks over a 52-week treatment period. The trial included a
post-treatment follow-up period of 12 weeks.1,3
Chronic Obstructive Pulmonary Disease (COPD)
COPD refers to a group of lung diseases, including chronic
bronchitis and emphysema, that cause airflow blockage and
breathing-related problems.4 COPD is the third leading cause of
death due to chronic disease and the sixth leading cause of
mortality in the United States. COPD accounts for the majority of
chronic lower respiratory mortality in the US at 150,000 deaths per
year, and data suggests patients with COPD are, on average, 50
times more likely to die from their condition compared to those
with asthma.5,6
The lungs and heart are fundamentally linked and work together.7
COPD mechanisms elevate the risk of both lung and heart events,
including severe or even fatal COPD exacerbations and cardiac
events, known as cardiopulmonary risk.8-11 Approximately 1 in 5
patients with COPD will die within a year of their first
hospitalization for an exacerbation, and pulmonary and cardiac
events are a key driver of mortality and the most common reasons
for death in patients with COPD.8,12-14
TEZSPIRE
TEZSPIRE (tezepelumab) is being developed by AstraZeneca in
collaboration with Amgen as a first-in-class human monoclonal
antibody that inhibits the action of TSLP, a key epithelial
cytokine that sits at the top of multiple inflammatory cascades and
is critical in the initiation and persistence of allergic,
eosinophilic and other types of airway inflammation associated with
severe asthma, including airway hyperresponsiveness.15,16 TEZSPIRE
is approved in the US, EU, Japan and other countries for the
treatment of severe asthma.17-19
Amgen collaboration
In 2020, Amgen and AstraZeneca updated a 2012 collaboration
agreement for TEZSPIRE. Both companies will continue to share costs
and profits equally after payment by AstraZeneca of a mid
single-digit inventor 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, Amgen and
AstraZeneca will jointly commercialize TEZSPIRE in North America.
Amgen will record product sales in the US, with AZ recording its
share of US profits as Collaboration Revenue. Outside of the US,
AstraZeneca will record product sales, with Amgen recording profit
share as Other/Collaboration revenue.
In addition, we are also collaborating with AstraZeneca on
AMG104/AZD8630, an inhaled anti-TSLP compound currently in
development for asthma. In November 2021, Amgen and AstraZeneca
agreed to include AMG 104 / AZD8630 in the existing collaboration
agreement. The companies share both costs and income, with no
inventor royalty. AstraZeneca will be the development,
manufacturing and commercial lead. AstraZeneca and Amgen will
jointly commercialize AMG 104 / AZD8630 in North America, and
AstraZeneca will distribute the product and book sales globally,
including for the US.
Respiratory & Immunology
Respiratory & Immunology, part of BioPharmaceuticals, is one
of AstraZeneca’s main disease areas and is a key growth driver for
the Company.
AstraZeneca is an established leader in respiratory care with a
50-year heritage. The Company aims to transform the treatment of
asthma and COPD by focusing on earlier biology-led treatment,
eliminating preventable asthma attacks, and removing COPD as a
top-three leading cause of death. The Company’s early respiratory
research is focused on emerging science involving immune
mechanisms, lung damage and abnormal cell-repair processes in
disease and neuronal dysfunction.
With common pathways and underlying disease drivers across
respiratory and immunology, AstraZeneca is following the science
from chronic lung diseases to immunology-driven disease areas. The
Company’s growing presence in immunology is focused on five mid- to
late-stage franchises with multi-disease potential, in areas
including rheumatology (including systemic lupus erythematosus),
dermatology, gastroenterology, and systemic eosinophilic-driven
diseases. AstraZeneca’s ambition in Respiratory & Immunology is
to achieve disease modification and durable remission for millions
of patients worldwide.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines in Oncology, Rare Diseases and
BioPharmaceuticals, including Cardiovascular, Renal &
Metabolism, and Respiratory & Immunology. Based in Cambridge,
UK, AstraZeneca operates in over 100 countries, and its innovative
medicines are used by millions of patients worldwide. For more
information, please visit www.astrazeneca-us.com and follow us on
social media @AstraZeneca.
References
- Singh D, et al. Tezepelumab in adults with moderate to very
severe chronic obstructive pulmonary disease (COPD): efficacy and
safety from the phase 2a COURSE study. American Thoracic Society
(ATS) 2024. May 2024.
- Data on File REF-228444 – Blood Eosinophil Count in 65% COPD
patients.
- Clinicaltrials.gov. Tezepelumab COPD Exacerbation Study
(COURSE) [Online]. Available at:
https://clinicaltrials.gov/ct2/show/NCT04039113. [Last accessed:
May 2024].
- GOLD. Global Strategy for the Diagnosis, Management and
Prevention of COPD, Global Initiative for Chronic Obstructive Lung
Disease (GOLD), 2023. [Online]. Available at: http://goldcopd.org.
[Last accessed: May 2024].
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https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. [Last
accessed: May 2024].
- National Heart, Lung, and Blood Institute (NIH). Learn More
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2024].
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Relationship (2023) Available at:
https://www.lung.org/blog/heart-lung-relationship. [Last accessed:
May 2024].
- Ho TW, Tsai YJ, Ruan SY, et al. In-Hospital and One-Year
Mortality and Their Predictors in Patients Hospitalized for
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Nationwide Population-Based Study. PLOS ONE. 2014; 9 (12):
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- Donaldson GC et al. Increased risk of myocardial infarction and
stroke following exacerbation of COPD. Chest.
2010;137:1091-1097;9-2029.
- Watz H et al. Spirometric changes during exacerbations of COPD:
A post hoc analysis of the WISDOM trial. Respir Res.
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- Suissa S et al. Long-term natural history of chronic
obstructive pulmonary disease: severe exacerbations and mortality.
Thorax. 2012;67(11):957-963.
- Lindenauer PK, Dharmarajan K, Qin L, et al. Risk Trajectories
of Readmission and Death in the First Year After Hospitalization
for Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care
Med. 2018 Apr 15;197(8):1009-1017.
- García-Sanz MT, Cánive-Gómez JC, Senín-Rial L, et al. One-year
and long-term mortality in patients hospitalized for chronic
obstructive pulmonary disease. J Thorac Dis. 2017; 9 (3): 636‐645.
doi:10.21037/jtd.2017.03.34.
- Mannino DM et al. Global Initiative on Obstructive Lung Disease
(GOLD) classification of lung disease and mortality: findings from
the Atherosclerosis Risk in Communities (ARIC) study. Respir Med.
2006;100: pp.115-122.
- Corren J, et al. Tezepelumab in adults with uncontrolled asthma
[supplementary appendix; updated April 18, 2019]. N Engl J Med.
2017;377:936-946.
- Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms,
Inflammatory Disorders, and Cancer. Front Immunol.
2018;9:1595.
- AstraZeneca plc. Tezspire (tezepelumab) approved in the US for
severe asthma. Available at:
https://www.astrazeneca.com/media-centre/press-releases/2021/tezspire-tezepelumab-approved-in-the-us-for-severe-asthma.html.
[Last accessed: May 2024].
- AstraZeneca plc. Tezspire approved in the EU for the treatment
of severe asthma. 2022. Available at:
https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/tezspire-approved-in-the-eu-for-the-treatment-of-severe-asthma.html.
[Last accessed: May 2024].
- AstraZeneca plc. Tezspire approved in Japan for the treatment
of severe asthma. Available at:
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[Last accessed: May 2024].
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