Phase 2 findings presented at ATS 2026 by Gerald Criner, MD, show pegtarazimod cut supplemental oxygen needs in hospitalized AE-COPD patients for up to 60 days.
A phase 2 proof-of-concept trial presented at the
Gerard J. Criner, MD, ATSF, FCCP, FACP, from Lewis Katz School of Medicine at Temple University, presented the findings and spoke with HCPLive at ATS 2026 about what the data mean for pulmonologists managing hospitalized COPD patients.
Hospitalized AE-COPD events carry significant clinical consequences: accelerated lung function decline, reduced quality of life, and increased mortality. Despite this burden, Criner noted that no therapies specifically targeting the acute exacerbation event have materially advanced in more than 50 years.
Neutrophilic inflammation drives the biology of acute exacerbations, and no existing therapy has proven capable of shifting outcomes for hospitalized patients. Criner said an effective therapy for neutrophilic inflammation could “change the tide” in patients admitted to the hospital.
“Pegtarazimod…which is a drug that's been used for [the] treatment of refractory chronic graft versus host disease, might uniquely fill the void to decrease neutrophilic inflammation in patients admitted to the hospital with COPD,” Criner said.
The agent inhibits the classical pathway of complement along with 2 key neutrophil inflammatory effectors—myeloperoxidase (MPO) and neutrophil elastase (NE)—positioning it as a targeted approach to the neutrophil-driven pathophysiology underlying many hospitalized AECOPD events.
The trial was a randomized, double-blind, placebo-controlled study enrolling hospitalized adults with AE-COPD. A total of 21 patients were enrolled, with 11 randomized to placebo and 10 to pegtarazimod as add-on therapy to usual care. The dosing regimen was 10 mg/kg IV 3 times daily for ≥ 3 days and up to 5 days. Participants were followed for efficacy and safety at 30 and 60 days after the final dose.
Primary oxygenation outcomes included change in fraction of inspired oxygen (FiO₂), oxygen saturation (O₂ sat), respiratory rate, and the ROX index, a validated calculation of SpO₂/FiO₂/respiratory rate used to predict intubation risk in acute hypoxic respiratory failure, where higher values indicate improved oxygenation and reduced work of breathing.
Compared to placebo, patients receiving pegtarazimod required less supplemental oxygen during hospitalization, as measured by decreased FiO₂, with that benefit sustained through the 60-day follow-up window. The treatment group also demonstrated increased blood oxygen saturation and improved ROX index scores relative to controls.
"Patients treated with pegtarazimod had a sooner improvement in oxygen saturation, a decrease in oxygen requirements, a slight improvement in lung function, and also an improvement in quality of life," Criner said.
No safety concerns were identified over the study period.
When patients were stratified by neutrophil-to-lymphocyte ratio (NLR), those with a high NLR—defined as > 9, consistent with strongly neutrophil-driven disease—showed the greatest respiratory benefit. This subgroup demonstrated less supplemental oxygen need, larger decreases in respiratory rate, and greater increases in the ROX index compared to patients with NLR below 9, aligning with pegtarazimod's mechanism of action.
Criner noted that while the NLR findings are based on a small sample, they are consistent with data from larger studies examining NLR as a marker of neutrophil-driven inflammation. The accessibility of NLR as a standard clinical lab value, rather than a specialized assay, could make it a practical patient selection tool if findings hold in larger trials.
Criner outlined what a definitive trial would require. A phase 2b study would need expanded enrollment, longer follow-up (a minimum of 6 months), and predefined efficacy endpoints targeting both mechanistic and clinical outcomes.
If replicated at scale, pegtarazimod could represent the first targeted anti-inflammatory strategy specifically designed for the acute hospitalized COPD setting, addressing a therapeutic gap that has persisted for half a century.
At ATS 2026, Criner also presented on pooled phase 3 data showing mepolizumab reduced COPD exacerbations and hospitalizations in patients with blood eosinophil counts starting at 150 cells/µL. Watch the interview here:
Editor’s note: Relevant disclosures for Criner include Pulmonx Corporation, GENZYME CORPORATION, GlaxoSmithKline, Olympus Corporation of the Americas, F. Hoffmann-La Roche AG, and AstraZeneca Pharmaceuticals.
References
