Amgen and AstraZeneca's Tezspire (tezepelumab) may offer a therapeutic benefit in chronic obstructive pulmonary disease (COPD) patients with elevated eosinophil counts, despite failing to meet the primary endpoint in a Phase 2a clinical trial. The COURSE study, presented at the American Thoracic Society (ATS) congress, revealed that Tezspire, an anti-TSLP antibody, did not achieve a statistically significant reduction in the annual rate of moderate to severe COPD exacerbations compared to placebo in the overall study population.
COURSE Trial Details
The Phase 2a COURSE study involved a mixed population of COPD patients, including individuals with and without emphysema and chronic bronchitis, a broad range of blood eosinophil counts, and variable smoking status. After 52 weeks, a non-significant 17% reduction in exacerbations was observed compared to the control group.
Subgroup Analysis Reveals Potential
However, a subgroup analysis showed a more promising outcome. In patients with a baseline eosinophil count (BEC) of 150 cells/μL or more, Tezspire demonstrated a 37% reduction in exacerbations. Amgen and AstraZeneca estimate that this subgroup represents approximately two-thirds of COPD patients who could be eligible for biologic treatment. Furthermore, in patients with even higher BEC levels of 300 cells/μL or more, Tezspire achieved a 46% reduction in moderate or severe exacerbations. The drug also showed trends towards improved outcomes in lung function scores and patient-reported outcomes (PRO) data.
Comparison to Dupixent
The results invite comparison with Sanofi and Regeneron's Dupixent (dupilumab), an IL-4 and IL-13 inhibitor currently under review by the US FDA for COPD. In the BOREAS and NOTUS trials, Dupixent reduced exacerbation rates by 30% and 34%, respectively, in patients with BEC levels of 300 cells/μL or above. While a direct comparison is premature, the Tezspire data suggest the potential for higher efficacy in specific patient subgroups, pending larger Phase 3 trials.
Future Directions
Jay Bradner, Amgen’s head of R&D, emphasized the continued need for effective COPD therapies, especially for patients with eosinophil counts above 150 cells/µL. "We are now actively planning a phase 3 clinical programme evaluating tezepelumab in patients with COPD," he stated.
Market Opportunity
Analysts at Evercore ISI have projected substantial sales for Dupixent in COPD, potentially reaching $3.5 billion. Amgen and AstraZeneca aim to tap into this market by extending the range of COPD patients who could benefit from biologic treatment with Tezspire. Launched in 2021, Tezspire generated $653 million in sales for severe asthma last year, driven by the introduction of a new self-injector version.
Other TSLP-targeting drugs are also in development for COPD, including Uniquity Bio’s solrikitug, which has received FDA clearance to begin Phase 2 trials.
