Tezepelumab decreases exacerbation rate, improves lung function, quality of life in COPD
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Key takeaways:
- As baseline blood eosinophil count went up, so did the impact of tezepelumab for several outcomes.
- Tezepelumab appeared to be safe in patients with COPD.
SAN DIEGO — Among patients with moderate to very severe COPD receiving tezepelumab vs. placebo, the annualized rate of exacerbations dropped by 17%, according to research presented at the American Thoracic Society International Conference.
“Tezepelumab is a monoclonal antibody that specifically blocks [thymic stromal lymphopoietin] from interacting with its receptor,” Dave Singh, MD, professor of respiratory pharmacology at the University of Manchester, said during his presentation.
Back in 2021, the FDA approved tezepelumab (Tezspire; Amgen, AstraZeneca) for add-on maintenance treatment of adults and children aged 12 years and older with severe asthma.
In the multicenter, randomized, double-blind, placebo-controlled phase 2a COURSE study, Singh and colleagues evaluated 333 adults (mean age, 67.2 years; 43.5% women; mean BMI, 27.3 kg/m2; 68.2% former smokers) with moderate to very severe COPD receiving triple inhaled therapy and still experiencing a minimum of two exacerbations in the past 12 months to determine the impact of 420 mg tezepelumab every 4 weeks vs. placebo on the annualized rate of moderate or severe COPD exacerbations at 52 weeks.
Researchers also analyzed drug safety and compared changes in baseline pre-bronchodilator FEV1, St. George’s Respiratory Questionnaire total scores and COPD Assessment Test total scores at week 52 between the two groups.
“This study did not limit the population by blood eosinophil count at baseline, by the presence of chronic bronchitis or not, or to current smokers vs. former smokers,” Robert Fogel, MD, vice president of global medical affairs in respiratory and immunology at AstraZeneca, told Healio.
Within this study population, 55.6% had chronic bronchitis and 57.7% had emphysema, according to the presentation.
To capture the drug’s impact across different exacerbation severities, researchers made sure that the study included patients with at least three moderate or severe COPD exacerbations in the past 12 months (approximately 40%) and patients with at least one severe COPD exacerbation in the past 12 months (approximately 30%).
This study also included patients with varying blood eosinophil counts (BECs) at screening. Singh said 41.1% had a count less than 150 cells/μL, 42% had a count of at least 150 cells/μL to less than 300 cells/μL and 16.8% had a count of at least 300 cells/μL.
Of the total cohort, 165 patients (mean age, 67.4 years; 46.7% women; BMI, 27.3 kg/m2) received tezepelumab, and 168 patients (mean age, 67.1 years; 40.5% women; BMI, 27.4 kg/m2) received placebo.
Singh also highlighted that 20.7% of the total population had high nitric oxide (≥ 25 ppb), whereas the remaining 79.3% had nitric oxide less than 25 ppb.
Findings
Although the primary outcome did not reach statistical significance, a decrease in the annualized rate of moderate/severe COPD exacerbations was found among those receiving tezepelumab vs. placebo (rate ratio = 0.83; 95% CI, 0.61-1.11).
Dividing the cohort based on BECs revealed an even greater drop in exacerbation rate with tezepelumab, with decreases of 37% (rate ratio = 0.63; 95% CI, 0.43-0.93) in the 150 cells/μL or more count group, 34% (rate ratio = 0.66; 95% CI, 0.42-1.04) in the at least 150 cells/μL to less than 300 cells/μL count group and 46% (rate ratio = 0.54; 95% CI, 0.25-1.15) in the 300 cells/μL or more count group.
“This looks like to me that the above 150 [cells/μL] subgroup is a potential responder population,” Singh said during his presentation.
Notably, a higher number of exacerbations in the past 12 months also meant a greater decrease in exacerbation rate in the tezepelumab vs. placebo group (≥ 3 exacerbations, rate ratio = 0.7; 95% CI, 0.46-1.07; 2 exacerbations, rate ratio = 0.96; 95% CI, 0.64-1.45).
A similar trend was observed when researchers assessed the exacerbation rate based on nitric oxide levels, with a greater reduction in this rate with tezepelumab vs. placebo seen in the group with high levels (rate ratio = 0.46; 95% CI, 0.22-0.98) rather than low levels (rate ratio = 0.99; 95% CI, 0.69-1.43).
“That very much then goes with the greater effects when you put it with the eosinophil data, a greater effect in individuals who were biomarker positive for type 2 inflammation,” Singh said.
During the presentation, Singh highlighted a couple subgroups of interest, including age at study entry and chronic bronchitis.
Tezepelumab appeared to have a greater impact on exacerbation rate among individuals aged at least 40 years to less than 65 years (rate ratio = 0.55; 95% CI, 0.33-0.92) rather than those aged 65 years to 80 years (rate ratio = 1; 95% CI, 0.7-1.44), as well as those without chronic bronchitis (rate ratio = 0.66; 95% CI, 0.42-1.04) rather than those with this condition (rate ratio = 0.98; 95% CI, 0.66-1.47).
“My opinion here is that chronic bronchitis and emphysema have not been rigorously collected, so to me that page is unclear,” Singh said.
When taking a closer look at exacerbation rate according to BEC in a post hoc analysis, Singh pointed out how treatment response could be based on this count.
“At around 150 eosinophils, there seems to be a change in population characteristics,” he said during the presentation. “Above that level, we now enter a response population and below that level, these seem to be a population that did not respond to the intervention.”
To test this, researchers reevaluated exacerbation rates in four subgroups with the addition of a BEC of 150 cells/μL or more.
A BEC of 150 cells/μL or more plus nitric oxide level further reduced exacerbation rate with tezepelumab vs. placebo. Singh noted that in the lower level group plus this BEC, the rate dropped by 23% (rate ratio = 0.77; 95% CI, 0.49-1.23), and in the higher level group plus this BEC, the rate dropped by 83% (rate ratio = 0.17; 95% CI, 0.06-0.49).
In terms of age at entry, “these now move to a 62% reduction in younger individuals and a 23% reduction in individuals aged 65 to 80,” Singh said.
Researchers found similar decreases in exacerbation rate with tezepelumab when adding a BEC of 150 cells/μL or more to current vs. former smoking status and to two vs. at least three prior exacerbations.
Moving away from this post hoc analysis, Singh revealed a decrease in the annualized rate of severe COPD exacerbations among those receiving tezepelumab vs. placebo (rate ratio = 0.52; 95% CI, 0.24-1.11).
Compared with the placebo group, the tezepelumab group also showed better pre-bronchodilator FEV1 from baseline to week 52 (between group difference least-square mean change, 0.055 L; 95% CI, 0.014-0.096).
Health-related quality of life also improved more with tezepelumab vs. placebo at week 52, as seen through the between group difference in SGRQ total score (least square mean change, –2.93; 95% CI, –6.23 to 0.36) and CAT total score (least-square mean change, –1.86; 95% CI, –3.31 to –0.4).
Singh noted that changes in lung function and SGRQ score with tezepelumab vs. placebo were greater with higher BECs.
“The higher the eosinophil count, it seems to be the bigger the benefit,” he said during the presentation.
Safety, future research
In terms of safety, researchers found that patients in the tezepelumab group and patients in the placebo group experienced a comparable number of adverse events and serious adverse events.
Positive COVID-19 tests appeared more often in the tezepelumab vs. placebo group (n = 24 vs. n = 14), but Singh said that COVID-19 hospitalization did not differ between these two sets of patients.
“The safety and tolerability in this phase 2 study were consistent with what we know about the drug,” Singh said.
When asked about the impact of these findings for the everyday clinician, Singh told Healio he can only speculate at the moment.
“There might be a perception by the practicing clinician that biologics in COPD are for a minority of people who fit in a highly stringent eosinophil criteria,” Singh said. “I think that would be the big possible implication [of this study], that it would change the way you think about biologics in COPD, it’s not a niche population.”
Future research is expected to include more patients, Fogel and Singh told Healio.
“The next study or studies will be substantially larger as they are in phase 3, and the population may differ based on the learnings of what we’ve read out from COURSE,” Fogel said.
“I think we're changing perhaps the perception of what a biologic is,” Singh said. “A biologic has a broad anti-inflammatory rather than a selective treatment, and that really then informs your phase 3 design because you have to be careful not to be too selective to rule out people who can gain benefit.”
Reference:
- New data presented at ATS 2024 show the potential of TEZSPIRE to play a role in the future treatment of chronic obstructive pulmonary disease. https://www.astrazeneca-us.com/media/press-releases/2024/new-data-presented-at-ats-2024-show-the-potential-of-tezspire-to-play-a-role-in-the-future-treatment-of-chronic-obstructive-pulmonary-disease.html. Published May 19, 2024. Accessed May 22, 2024.