Tezspire's Effect on COPD Exacerbations May Hinge on Blood Eosinophil Counts | 2024 ATS

Tezspire (tezepelumab) did not have a pronounced, statistically significant effect on chronic obstructive pulmonary disorder (COPD) exacerbation in a general group of people with condition, according to results from a phase 2a study presented today at the 2024 American Thoracic Society (ATS) International Conference in San Diego. But the results of a prespecified analysis suggest that the monoclonal antibody is safe and efficacious in people whose COPD mauy be fueled, in part, by type 2 inflammation.

The results for Tezspire dovetail with those from a phase 3 trial of Dupixent (dupilumab) that was also presented at the meeting today that showed Dupixent was efficacious and safe in people with COPD with type 2 inflammation. These and other results are likely to stoke interest, investment and drug development efforts aimed at the 20% to 40% of COPD that has type 2 inflammation as a causative ingredient.

In both trials, the biologics, which are administered subcutaneously, were added on to the standard inhaled therapy for COPD that consists of three types of drugs: a glucocorticoid agent, a long-acting muscarinic antagonist and a long-acting beta-agonist. During the question and answer period of the presentation, audience raised questions about the cost effectiveness of adding the expensive biologics to the standard, inhaled “triple therapy” and further burdening COPD patients with more therapy.

Dave Singh

The FDA approved Tezspire in 2021 as treatment for severe asthma. Dave Singh, a professor a professor of respiratory pharmacology at the University of Manchester in England, who presented the Tezspire findings, told the ATS audience that the hope was that Tezspire would cast a wide net over COPD pathophysiology because it blocks the action of thymic stromal lymphopoietin, which he said is one of the master regulators of inflammation. In keeping with that notion, the, the phase 2a COURSE trial was designed to enroll a range of COPD patients, he explained.

“We wanted a broad population,” Singh said. “We wanted to answer the question, if there is efficacy, does this monoclonal antibody work in the whole population? And if not, is it subgroup.

Approximately 330 participants were enrolled in the trial. To be included they had to have two more exacerbations in the 12 months before enrollment. People with asthma or history of it were excluded, even if they had childhood asthma that went away with age. “This study was very rigorous in ensuring there was no diagnostic doubt,” Singh said.

Patients were randomly assigned to treatment every four weeks for 52 weeks with either 420 milligrams of Tezspire, which is twice the suggested dose when Tezspire is used to treat severe asthma, or a placebo. Both groups continued with inhaled triple therapy. The primary end point was same as the one used in the phase 3 Dupixent trial, the annualized rate of moderate or severe COPD exacerbations.

The results after 52 weeks showed annualized exacerbation rate among the patients in the Tezspire was 17% lower than the rate in the placebo group but the difference didn’t met the threshold for statistical significance. But then Singh and his colleagues analyzed the data through the lens of blood eosinophil counts, a standard biomarker for type 2 inflammation. Among those with blood eosinophil counts of 150 cells per microliter or higher, the 92 patients randomly assigned to Tezspire had annualized exacerbation rates that were 37% lower than the 102 randomly assigned to placebo. In those with blood eosinophil counts of 300 cells per microliter or higher, Tezspire reduced exacerbations further, by 46% relative to the placebo group.

Singh shared other analyses that suggest a pattern of the beneficial effects of Tezspire for people with COPD kicking in among those with blood eosinophil counts of 150 cells per microliter and increasing as the counts go up.

The Dupixent study was design to limit enrollment to those with blood eosinophil counts of 300 or more. There may be a lot of discussion about where to the draw the line on blood eosinophil counts. Singh also noted that counts tend to fluctuate more among those whose counts fall into a middle range.