Amgen and AstraZeneca have highlighted the potential of Tezspire (tezepelumab) in chronic obstructive pulmonary disease (COPD) in a subgroup of patients in a Phase IIb study even though the trial missed the primary endpoint.

The therapy failed to show a significant reduction in the annual rate of moderate to severe exacerbations compared to the placebo, the trial’s primary endpoint. The data from the placebo-controlled Phase IIa COURSE trial (NCT04039113) was presented at the American Thoracic Society (ATS) International Conference taking place in San Diego, US, from 16 to 21 May.

However, a pre-determined subgroup analysis of COPD patients based on the levels of eosinophils, measured as baseline eosinophil count (BEC), showed significant reductions in COPD exacerbations. The therapy also demonstrated a 48% reduction in severe exacerbations compared to the placebo.

Patients who received Tezspire while having a BEC of 150 cells/μL or more, which is associated with increased COPD-related emergency room visits and a higher exacerbation rate, showed a 37% reduction in the rate of moderate or severe exacerbations compared to placebo. In patients with BEC of 300 cells/μL or more, the Tezspire group demonstrated a 46% reduction in the rate of moderate or severe exacerbations compared to placebo.

“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,” said Sharon Barr, AstraZeneca’s executive vice president of Bio-Pharmaceuticals R&D.

“As a result of these promising data, we are actively in Phase III planning for Tezspire in COPD.”

Tezspire is a thymic stromal lymphopoietin (TSLP)-inhibiting monoclonal antibody. TSLP is an interleukin (IL)-2-like cytokine, alarmin, and growth factor that plays a key role in the immune system. It was approved by the US Food and Drug Administration (FDA) as a treatment for severe asthma in 2021.

The therapy’s main competitor in the space is Sanofi and Regeneron’s Dupixent (dupilumab). The IL-4/IL-13 inhibitor has already been approved to treat multiple immune-mediated disorders including asthma, with the FDA expected to decide on its use in COPD by the end of June.

Dupixent showed a 34% reduction in moderate or severe acute COPD exacerbations over 52 weeks in patients with SEC of at least 300 cells/μL, as per the data from the Phase III NOTUS trial (NCT04456673). A cross-trial comparison suggests that Dupixent may be less effective in reducing exacerbations compared to Tezspire, however, data from a Phase III trial with Tezspire is needed before an effective comparison can be made between the two therapies.

As per Sanofi’s financials, Dupixent earned €10.7bn ($11.6bn) in global sales last year. GlobalData forecasts the therapy revenue to maintain its upward trajectory and generate $20.4bn in sales in 2030.

Amgen and AstraZeneca are also investigating Tezspire in other conditions such as chronic rhinosinusitis with nasal polyps, chronic spontaneous urticaria, and eosinophilic esophagitis. In 2021, Tezspire received an orphan drug designation from the FDA for the treatment of EoE.

https://www.pharmaceutical-technology.com/news/amgen-and-astrazeneca-ponder-label-expansion-for-tezspire-in-copd/