New data presented at ATS 2024 show the potential of TEZSPIRE to play a role in the future treatment of chronic obstructive pulmonary disease

Rhea-AI Summary

New data from the Phase IIa COURSE trial suggests TEZSPIRE (tezepelumab) may reduce COPD exacerbations. The trial, involving 337 patients, showed a 17% reduction in annual COPD exacerbation rates compared to placebo, which was not statistically significant. However, in patients with blood eosinophil counts (BEC) ≥150 cells/µL, a significant 37% reduction was noted. For BEC ≥300 cells/µL, the reduction was 46%. Improvements in lung function and quality of life were also reported. Safety profiles were consistent with TEZSPIRE’s use in severe asthma. AstraZeneca and Amgen are planning Phase III trials based on these promising results.

Positive

• 37% reduction in COPD exacerbations in patients with BEC ≥150 cells/µL.
• 46% reduction in COPD exacerbations in patients with BEC ≥300 cells/µL.
• Improvement in lung function (FEV1): 63mL for BEC ≥150 cells/µL and 146mL for BEC ≥300 cells/µL.
• Improvement in quality of life (SGRQ score): 4.2 points for BEC ≥150 cells/µL and 9.5 points for BEC ≥300 cells/µL.
• Safety profile consistent with TEZSPIRE’s severe asthma indication.

Negative

• 17% reduction in annual COPD exacerbation rate was not statistically significant.
• Adverse events: 12.1% worsening of COPD and 14.5% incidents of COVID-19 infections.
• Phase IIa results show impact on patients with BEC <150 cells/µL.

Insights

Medical Research Analyst

TEZSPIRE's Phase IIa results for COPD present a mix of signals for investors. While the 17% reduction in exacerbations isn't statistically significant, the results among specific subgroups—like those with higher blood eosinophil counts (BEC)—show promise. For example, patients with BEC ≥150 cells/µL saw a 37% reduction in exacerbations and those with BEC ≥300 cells/µL saw a 46% reduction. These figures are more encouraging, suggesting that TEZSPIRE could have a targeted efficacy in certain patient populations.

However, the small sample sizes in these subgroups and the broad confidence intervals indicate a need for further investigation. The nominal significance and numerical improvements in lung function (FEV1) and quality of life (SGRQ scores) also support this. Investors should note that while these Phase IIa results are promising, they are not conclusive. AstraZeneca and Amgen moving to Phase III trials will be important in determining TEZSPIRE’s future in COPD treatment.

In short-term, the results might not greatly affect stock prices due to the non-significant overall findings. Long-term, the drug’s potential in targeted subgroups could influence market dynamics positively if Phase III results validate these findings.

Financial Analyst

From a financial standpoint, TEZSPIRE's Phase IIa results provide a double-edged sword. The non-significant overall reduction in exacerbations (17%) at week 52 could temper immediate investor excitement. However, the potential efficacy in subgroups with higher eosinophil counts could signal a lucrative market opportunity if further trials demonstrate significant results. The initiation of Phase III planning is a positive indicator of AstraZeneca and Amgen's confidence in overcoming these initial hurdles.

It's also noteworthy that TEZSPIRE is already approved for severe asthma, which could expedite its market penetration for COPD if subsequent trials are successful. Investors should keep an eye on the cost implications of these extensive trials and the competitive landscape, particularly considering the costs and profits sharing agreement between AstraZeneca and Amgen. The success in Phase III could lead to substantial revenue growth, but risks remain high until conclusive results are achieved.

In terms of short-term financial impact, the market may respond cautiously to this news, reflecting the mixed results. Long-term prospects will hinge on the outcomes of the upcoming Phase III trials and the broader respiratory market dynamics.

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

WILMINGTON, Del.--(BUSINESS WIRE)-- 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

1. 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.
2. Data on File REF-228444 – Blood Eosinophil Count in 65% COPD patients.
3. Clinicaltrials.gov. Tezepelumab COPD Exacerbation Study (COURSE) [Online]. Available at: https://clinicaltrials.gov/ct2/show/NCT04039113. [Last accessed: May 2024].
4. 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].
5. Centers for Disease Control and Prevention (CDC). Leading Causes of Death. United States: CDC; January 17, 2024, https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. [Last accessed: May 2024].
6. National Heart, Lung, and Blood Institute (NIH). Learn More Breathe Better: United States: NIH. https://www.nhlbi.nih.gov/BreatheBetter. [Last accessed: May 2024].
7. American Lung Association. Your Heart and Lungs: The Ultimate Relationship (2023) Available at: https://www.lung.org/blog/heart-lung-relationship. [Last accessed: May 2024].
8. Ho TW, Tsai YJ, Ruan SY, et al. In-Hospital and One-Year Mortality and Their Predictors in Patients Hospitalized for First-Ever Chronic Obstructive Pulmonary Disease Exacerbations: A Nationwide Population-Based Study. PLOS ONE. 2014; 9 (12): e114866.
9. Donaldson GC et al. Increased risk of myocardial infarction and stroke following exacerbation of COPD. Chest. 2010;137:1091-1097;9-2029.
10. Watz H et al. Spirometric changes during exacerbations of COPD: A post hoc analysis of the WISDOM trial. Respir Res. 2018;19(1):251.
11. Suissa S et al. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012;67(11):957-963.
12. 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.
13. 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.
14. 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.
15. Corren J, et al. Tezepelumab in adults with uncontrolled asthma [supplementary appendix; updated April 18, 2019]. N Engl J Med. 2017;377:936-946.
16. Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018;9:1595.
17. 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].
18. 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].
19. AstraZeneca plc. Tezspire approved in Japan for the treatment of severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2022/tezspire-approved-in-japan-for-severe-asthma.html. [Last accessed: May 2024].

 

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FAQ

What are the latest results of the TEZSPIRE Phase IIa COURSE trial for COPD?

The trial showed a 17% reduction in annual COPD exacerbation rates, which was not statistically significant. However, significant reductions were seen in patients with BEC ≥150 cells/µL and ≥300 cells/µL.

How did TEZSPIRE perform in patients with different eosinophil levels in the COURSE trial?

TEZSPIRE led to a 37% reduction in exacerbations for BEC ≥150 cells/µL and a 46% reduction for BEC ≥300 cells/µL.

What was the impact of TEZSPIRE on lung function in the COURSE trial?

TEZSPIRE improved lung function by 63mL in patients with BEC ≥150 cells/µL and by 146mL in patients with BEC ≥300 cells/µL.

What adverse events were reported in the TEZSPIRE COURSE trial?

The most common adverse events were worsening of COPD (12.1%) and COVID-19 infections (14.5%).

What are the future plans for TEZSPIRE in COPD treatment?

Based on the promising Phase IIa results, AstraZeneca and Amgen are planning Phase III trials for TEZSPIRE in COPD.