First Half 2026 Recap - Pulmonology

H1 2026 was a defining period for pulmonology, bookended by a landmark COPD biologic program, a first-in-class antifibrotic context from late 2025 entering routine practice, and the most consequential IPF trial readout in years. The 2026 American Thoracic Society (ATS) International Conference served as the half-year's clinical centerpiece in May, while the American Academy of Allergy, Asthma & Immunology meeting in February and CHEST's first severe asthma biologic guideline in January set the tone for a field actively translating emerging evidence into prescribing frameworks.

Tozorakimab's triple phase 3 win across the OBERON, TITANIA, and MIRANDA trials positioned the IL-33 inhibitor as the first COPD biologic with a biomarker-agnostic efficacy signal, while nebulized treprostinil's TETON-1 data — including the first significant DLCO improvement in any phase 3 IPF trial — arrived at ATS with a supplemental NDA planned for summer 2026. Across asthma, real-world PASSAGE data extended tezepelumab's reach into populations long excluded from pivotal trials, ralinepag demonstrated a 55% PAH worsening reduction in ADVANCE OUTCOMES, and the BGF triple inhaler gained approval for patients as young as 12.

Here's a concise overview of the key pulmonology stories from H1 2026.

New CHEST Recommendations Guide Biologic Use for Severe Asthma

CHEST published its first guideline dedicated to choosing and sequencing biologics in severe asthma in January 2026, offering 7 evidence-based recommendations that give clinicians long-needed structure for managing patients who fail initial therapy. The guideline conditionally favors dupilumab for patients with frequent exacerbations or steroid dependence, while recommending anti–IL-5/5Rα agents in steroid-dependent patients with very high eosinophil counts; tezepelumab is positioned as a preferred switch option for patients failing dupilumab with low eosinophils or low FeNO. It also uses post-treatment FeNO ≥25 ppb as a signal to guide switching from anti–IL-5/5Rα to dupilumab — the first guideline to operationalize this marker in the step-therapy decision.

Related coverage: Eosinophils, Exacerbations, and Endpoints: Biologic Therapy Selection in COPD and Asthma

Phase 2 VALIANT: Verekitug Reduces Annual Asthma Flare-Ups

Upstream Bio announced in February 2026 that verekitug met its primary endpoint in the phase 2 VALIANT trial, demonstrating statistically significant reductions in annualized asthma exacerbation rate compared with placebo in adults with severe asthma. The TSLP receptor antagonist — which blocks TSLP signaling at the receptor level rather than targeting the cytokine directly — achieved a 56% exacerbation reduction at the 100 mg every-12-weeks dose, a less frequent administration schedule than any currently approved biologic in the class. Upstream Bio has announced plans to advance verekitug into phase 3 trials in severe asthma and chronic rhinosinusitis with nasal polyps.

IL-33 Inhibitor Tozorakimab Cuts COPD Exacerbations in Phase 3 OBERON and TITANIA

AstraZeneca announced in March 2026 that tozorakimab met its primary endpoint in both the phase 3 OBERON and TITANIA trials, becoming the first IL-33–targeting biologic to demonstrate statistically significant reductions in COPD exacerbations across 2 replicate confirmatory trials. Efficacy extended across all blood eosinophil levels and lung function severity stages, positioning tozorakimab as a potential biomarker-agnostic option for the large proportion of COPD patients who remain ineligible for or inadequately served by current eosinophil-gated biologics. Full efficacy and safety data had not yet been published in peer-reviewed form at the time of the announcement.

Related coverage: Reducing COPD Exacerbations With Tozorakimab, With Frank Sciurba, MD

Phase 3 MIRANDA Trial Links Tozorakimab to Fewer COPD Exacerbations

AstraZeneca announced in April 2026 that tozorakimab met its primary endpoint in the phase 3 MIRANDA trial — a third consecutive positive COPD exacerbation readout within the LUNA program — reducing annualized moderate-to-severe exacerbation rates vs placebo in former smokers and in the overall population, including current smokers across all eosinophil levels and lung function severity stages, with 300 mg subcutaneously every 2 weeks on top of inhaled standard of care. MIRANDA evaluated a more frequent dosing regimen than OBERON and TITANIA and further consolidates the evidence base ahead of anticipated regulatory submissions. Two additional LUNA trials — PROSPERO, a long-term extension, and UMBRIEL, a dose-ranging asthma study — remain ongoing.

Related coverage: OBERON and TITANIA Showcase Tozorakimab's Emerging Benefit for COPD, With Frank Sciurba, MD

FDA Approves BGF Triple Inhaler for Patients Aged 12 and Older

The FDA approved budesonide/glycopyrrolate/formoterol fumarate (BREZTRI Aerosphere; AstraZeneca) as the first single-inhaler ICS/LABA/LAMA triple combination for patients aged 12 and older in April 2026, extending a treatment paradigm previously limited to adults into adolescent patients with asthma or COPD. The approval was grounded in phase 3 KALOS and LOGOS data, published in The Lancet Respiratory Medicine, which showed a pooled 76 mL improvement in trough FEV₁ and a reduction in severe exacerbations compared to dual therapy. The pediatric and adolescent label expansion addresses a population previously managed with separate controller agents, reducing inhaler complexity.

Related coverage: BGF Triple Therapy FDA Approval Expands Asthma Options for Underserved Patients, With Juanita Mora, MD

Inhaled Treprostinil Improves IPF Outcomes in Phase 3 TETON-1 Trial

Nebulized treprostinil (Tyvaso; United Therapeutics) reduced FVC decline by 130.1 mL vs placebo (95% CI, 82.2 to 178.1; P <.001) and cut the risk of composite clinical worsening by 33% (HR, 0.67; P =.003) in the phase 3 TETON-1 trial, presented at ATS 2026 in May. In a combined analysis with TETON-2 enrolling more than 1000 patients, the program met 5 of 6 secondary endpoints — including a 48% reduction in acute exacerbations (P =.0223) and the first statistically significant DLCO improvement demonstrated by any IPF therapy in a phase 3 trial. United Therapeutics plans to submit a supplemental NDA by summer 2026 seeking priority review for the IPF indication, which would make nebulized treprostinil the first inhaled therapy approved for the condition.

Tezepelumab Reduces Severe Asthma Across Phenotypes in Phase 4 PASSAGE

Phase 4 PASSAGE data presented at ATS 2026 showed tezepelumab, an anti-TSLP monoclonal antibody, reduced annualized asthma exacerbation rates by 70% (95% CI, 63 to 75) over 52 weeks in a 286-patient real-world US cohort that included active smokers, patients with mild-to-moderate comorbid COPD, and Black or African American patients — populations historically excluded from biologic trials. Exacerbation reductions ranged from 54% to 77% across subgroups regardless of eosinophil count or allergic status, with clinically meaningful gains also seen in lung function and validated asthma control and quality-of-life measures. The findings may inform biologic eligibility decisions for patients previously excluded from pivotal programs on the basis of smoking history or airflow obstruction.

Ralinepag Achieves 55% Risk Reduction in PAH in Phase 3 ADVANCE OUTCOMES

Ralinepag, an investigational once-daily oral prostacyclin receptor agonist, reduced the risk of clinical worsening in pulmonary arterial hypertension by 55% vs placebo (HR, 0.45; P <.0001) in the phase 3 ADVANCE OUTCOMES trial, presented at ATS 2026 by Vallerie McLaughlin, MD, director of the pulmonary hypertension program at the University of Michigan. Secondary endpoints demonstrated significant NT-proBNP reductions, improved 6-minute walk distance, and 47% greater odds of clinical improvement; United Therapeutics has announced plans for an FDA new drug application submission in the second half of 2026. The agent's higher potency relative to existing prostacyclin pathway agents may offer more complete pathway activation, though head-to-head comparative data are not yet available.

FDA Clears LEADOPTIK's LIA System for Higher-Accuracy Lung Biopsy

The FDA granted 510(k) clearance in January 2026 to LEADOPTIK's Last Inch Assessment (LIA) system, a first-of-its-kind device that embeds high-resolution depth imaging directly into biopsy needles to provide real-time confirmation of tissue sampling at the target site. Preclinical data showed biopsy accuracy exceeding 95%, with the system offering approximately 50-fold better imaging resolution than existing technologies — addressing a persistent limitation in bronchoscopic biopsy procedures where off-target sampling contributes to diagnostic delays in lung cancer. The clearance arrives as expanded screening programs continue to identify more patients with early pulmonary lesions requiring tissue characterization, making procedural accuracy an increasingly consequential variable in the diagnostic workflow.

Mepolizumab COPD Pooled Analysis Supports Use Across Broader Eosinophil Range

A pooled analysis of the phase 3 METREX, METREO, and MATINEE trials presented at AAAAI 2026 in February found that mepolizumab reduced the annualized rate of COPD exacerbations requiring emergency department visits or hospitalization by 23% vs placebo (rate ratio, 0.77; 95% CI, 0.60 to 0.99; P =.044) in a combined population of 1713 patients with blood eosinophil counts ≥150 cells/µL at screening and/or ≥300 cells/µL in the prior year. The 19% reduction across the broader moderate-to-severe exacerbation endpoint supports mepolizumab's clinical utility at eosinophil thresholds below those most commonly discussed in prescribing practice;