Njira Lugogo, MD, from University of Michigan.

Njira Lugogo, MD

New subgroup data from the phase 2b AIRCULES trial show that lunsekimig, Sanofi's bispecific Nanobody targeting both thymic stromal lymphopoietin (TSLP) and interleukin-13 (IL-13), produced larger exacerbation reductions in patients with more severe or biomarker-high 

, according to Njira Lugogo, MD, MS, clinical professor of medicine and director of the Michigan Medicine Asthma Program at the University of Michigan. Lugogo discussed the data, presented at the 

European Respiratory Society (ERS) Congress 2026

 in Barcelona, Spain, held September 5 to 9, in an interview with 

AIRCULES Subgroup Data Show Lunsekimig Benefit Scales With Severity

“I'm really excited about lunsekimig specifically because this is the first bispecific biologic that we have in asthma,” she said, noting that most existing biologics target a single pathway despite evidence of redundant, overlapping inflammatory mechanisms in severe disease.

AIRCULES previously met its primary and key secondary endpoints compared with placebo, with lunsekimig added to standard of care in adults with moderate-to-severe asthma across the full range of fractional exhaled nitric oxide (FeNO) and eosinophil values.

 Lugogo said the annualized exacerbation reduction was about 39% in the overall population, rising to 55% at the highest dose tested (300 mg every 4 weeks). The effect was more pronounced in prespecified subgroups: patients with a history of more than 3 exacerbations had nearly an 80% reduction, those with high baseline FeNO had a significant exacerbation reduction alongside a lung function improvement and met the minimal clinically important difference on the Asthma Control Questionnaire, and patients with eosinophil counts above 300 cells/µL also showed a more robust response than the overall population, including improved forced expiratory volume in 1 second.

Lugogo said the dual-target mechanism has a specific rationale beyond simply combining 2 pathways: blocking TSLP upstream may help offset the eosinophil increase sometimes seen with IL-13 blockade alone, while both pathways have independently been linked to mucus reduction and lung function improvement. She also pointed to lunsekimig's potential to address comorbid type 2 conditions, such as sinonasal disease and atopic dermatitis, beyond asthma itself, based in part on her own clinical experience using dual-biologic combinations in patients with overlapping disease. On safety, she said the novel Nanobody platform showed a low rate of anti-drug antibodies and treatment-emergent adverse events similar between placebo and treatment arms, with no signals prompting concern heading into phase 3.

Lugogo said the subgroup data are meant to inform which patients should be prioritized in the phase 3 program and to help settle on a single dose going forward. She framed the results within a broader unmet need: only about 35% of patients with severe asthma currently achieve remission, and she said dual-pathway blockade could help expand that proportion. An early-intervention study of lunsekimig in high-risk patients, AIRLYMPUS, is expected to read out results next year.

Lugogo’s disclosures include AbbVie, Amgen, Apogee Therapeutics, AstraZeneca, Foresee Pharmaceuticals, Genentech, GSK, Incyte, Niox, Regeneron, Sanofi and Teva Pharmaceuticals.

Sanofi. Sanofi's lunsekimig met primary and key secondary endpoints in phase 2 respiratory studies in asthma and CRSwNP. Published April 7, 2026.

ClinicalTrials.gov. A study of lunsekimig (SAR443765) in adult participants with moderate to severe asthma (AIRCULES). Identifier: NCT06102005.

Articles

Lunsekimig, a bispecific Nanobody targeting TSLP and IL-13, showed enhanced exacerbation reduction in moderate-to-severe asthma, with larger effects in severe and biomarker-high subgroups. Overall annualized exacerbations fell ~39%, increasing to ~55% at 300 mg every 4 weeks. Patients with >3 prior exacerbations approached ~80% reduction, while high FeNO and eosinophils >300 cells/µL correlated with greater clinical benefit, including improved FEV1 and ACQ minimal clinically important difference attainment. Safety appeared comparable to placebo with low immunogenicity.

Phase 2b subgroup data showed lunsekimig's exacerbation benefit scaled with asthma severity and biomarker levels.

AIRCULES: Lunsekimig Benefit Scales With Severity, With Njira Lugogo, MD

Emerging data on STAT6 pathway inhibition was among the most interesting themes at this year's 

 in Barcelona, Spain, held September 5 to 9, according to Njira Lugogo, MD, MS, clinical professor of medicine and director of the Michigan Medicine 

 Program at the University of Michigan. Lugogo discussed the mechanism in an interview with 

, pointing to new data on KT-621, Kymera Therapeutics' investigational oral STAT6 degrader, presented as a poster at the congress.

STAT6 Degraders: Accessible Biologic-Like Asthma Care? With Njira Lugogo, MD

STAT6 sits downstream of both interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling, meaning it functions as a shared pathway before either cytokine's inflammatory effects are produced. Lugogo noted that dupilumab is currently the only approved therapy that blocks both IL-4 and IL-13 simultaneously, and it does so indirectly, by targeting the IL-4 receptor alpha subunit. 

“We could imagine a time where we have an oral drug that has the ability to replicate what we're doing with biologics, and that really opens the space entirely,” she said. 

In the phase 1b BroADen trial of KT-621 in patients with atopic dermatitis and comorbid respiratory disease, the subgroup with asthma had a median 56% reduction in fractional exhaled nitric oxide and a 100% Asthma Control Questionnaire-5 responder rate by day 29.

 Kymera is now running BREADTH, a placebo-controlled, dose-ranging phase 2b trial of KT-621 in moderate to severe eosinophilic asthma, with topline data on forced expiratory volume in 1 second expected in late 2027.

Lugogo outlined several ways an oral STAT6 degrader could fit into practice beyond simply mirroring existing biologics. One is as an add-on for patients already on a biologic who are only partial responders, particularly those with discordant upper and lower airway disease not addressed by their current mechanism. A second is as a pre-biologic option for patients who have maximized inhaled therapy but are not clear candidates for a biologic, or who live where biologic access is limited by logistical barriers such as cold-chain delivery. A third is in early intervention trials for high-risk populations, an area she said is drawing growing interest across several biologic classes and could benefit from a more accessible oral option. She also raised the possibility of using a STAT6 degrader as an inhaled corticosteroid (ICS)-sparing add-on therapy, given increasing attention to the safety trade-offs of sustained high-dose ICS exposure.

Lugogo said the underlying opportunity is one of access: targeted asthma therapy is currently reserved largely for the most severe patients, and an oral option could extend biologic-like benefit to a much broader population. “It's very early. It's emerging, but I think it's extremely promising,” she said, adding that she plans to closely follow the STAT6 field over the next several years.

Feldman MB, Gollob J, Dey J, Shi K, Agarwal S, Graham N, Mainolfi N. KT-621, an oral STAT6 degrader, in patients with moderate-to-severe atopic dermatitis and comorbid asthma or allergic rhinitis: safety and evidence of clinical activity across type 2 inflammatory diseases in a phase 1b trial. Poster PA5913. Presented at: European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.

Kymera Therapeutics, Inc. Kymera Therapeutics announces presentations on KT-621, a first-in-class, oral STAT6 degrader, at the European Respiratory Society and European Academy of Dermatology & Venereology congresses. Published September 1, 2026.

Videos

Lugogo, ofUniversity of Michigan, discusses how oral STAT6 degraders like KT-621 could expand biologic-like asthma treatment beyond highest severity.

Tezepelumab Reduces Severe Asthma Exacerbations by 70% in Phase 4 PASSAGE

Real-world phase 4 PASSAGE data presented at the 2

026 American Thoracic Society (ATS) International Conference 

in Orlando, Florida, found that tezepelumab (Tezspire) reduced severe asthma exacerbations by 70%. The treatment also improved disease control across a diverse population of patients with severe uncontrolled 

, including groups routinely excluded from or underrepresented in pivotal trials.

 at ATS 2026, Njira Lucia Lugogo, MD, clinical professor of medicine in the Division of Pulmonary and Critical Care Medicine at the University of Michigan, discussed the implications of the data for real-world prescribing and the need for more inclusive trial design going forward.

PASSAGE Study Design: Real-World Severe Asthma Cohort

PASSAGE was a phase 4, multicenter, single-arm, open-label study enrolling patients aged ≥ 12 years with severe asthma and ≥ 2 exacerbations in the prior year. The 286-patient cohort was intentionally designed to reflect populations underrepresented in randomized controlled trials: 42% had blood eosinophil counts (BEC) ≥ 300 cells/µL, 58% had a positive allergy status, 22% were Black or African American, 7% were adolescents, 20% had comorbid COPD, and 29% were current or former smokers.

Tezepelumab Reduced Annualized Asthma Exacerbation Rate by 70% Overall

The annualized asthma exacerbation rate (AAER) decreased by 70% (95% CI: 63 to 75) from baseline to the treatment period overall. Across asthma phenotypes and underrepresented subgroups, reductions ranged from 54% to 77%, indicating consistent benefit regardless of eosinophil status, smoking history, or comorbid COPD.

"When we scaled up from the very homogeneous clinical trial population to a real-world population, we are replicating the effects and maybe even seeing more profound exacerbation reduction, which is very reassuring," Lugogo told 

. "It should give us the confidence that we can use these drugs in clinical practice successfully."

Tezepelumab Improved FEV1, with Greater Gains in Patients with Impaired Lung Function

At week 52, the least-squares mean change in pre-bronchodilator FEV1 from baseline was 0.12 L (95% CI: 0.07 to 0.17) overall (n = 222). Among patients with baseline FEV1 ≤ 80% predicted — those with the most compromised lung function at enrollment — the improvement was greater, at 0.21 L (95% CI, 0.15 to 0.28; n = 138).

Clinically Meaningful Improvements in Asthma Control and Quality of Life

Clinically meaningful improvements from baseline, defined by minimum clinically important difference thresholds, were observed at week 52 across three validated instruments. Among the overall population (all n = 219), 74% achieved meaningful improvement on the Asthma Control Questionnaire-6 (ACQ-6), 63% on the Asthma Impairment and Risk Questionnaire (AIRQ), and 80% on the St. George's Respiratory Questionnaire (SGRQ). Across asthma phenotypes and underrepresented populations, response rates ranged from 64 to 86% for ACQ-6, 51 to 75% for AIRQ, and 63 to 91% for SGRQ.

Tezepelumab Efficacy in Black/African American Patients with Severe Asthma

Black and African American patients comprised 22% of the PASSAGE cohort, which is a proportion greater than what is typically seen in phase 3 severe asthma trials. Lugogo noted that this population responded well to tezepelumab without new safety signals and framed the findings in the context of a broader access gap.

"Many biologic-eligible patients are simply not receiving any biologic, so I'm hoping that this new data…is going to give us more confidence, and we'll be able to increasingly use biologics in wider patient populations,” Lugogo said.

Tezepelumab Safety Profile Consistent With Prior Trial Data

In total, 28 patients (9.8%) experienced a serious adverse event during the treatment period following tezepelumab initiation. Adverse events were consistent with the established safety profile of the drug.

PASSAGE Highlights Gaps in Severe Asthma Trial Design

Beyond the clinical findings, Lugogo called for a broader reconsideration of how severe asthma trials are structured. Patients with comorbid asthma-COPD overlap remain ineligible for most interventional trials, leaving clinicians without prospective evidence until post-authorization studies like PASSAGE are completed.

"We need to think about whether we need a paradigm shift in how we design our trials to include some of these comorbid populations so that we can have data a bit earlier and not have to wait for data generation afterwards,” Lugogo said.

Watch part 1 of our interview with Lugogo here: 

Tezepelumab Reduced Severe Asthma Across Phenotypes in Phase 4 PASSAGE.

Editor’s note: Relevant disclosures for Lugogo include GlaxoSmithKline, GENZYME CORPORATION, SANOFI-AVENTIS U.S., AstraZeneca Pharmaceuticals, Regeneron Pharmaceuticals, Incyte Corporation, and more.

Lugogo NL, Akuthota P, Sumino K, et al. (

) Tezepelumab in diverse real-world patients with severe asthma across different phenotypes and underrepresented populations: final results from the US phase 4 PASSAGE study. Late-breaking research was presented at the American Thoracic Society 2026 International Conference on May 18 in Orlando, Florida.

Phase 4 PASSAGE data from ATS 2026 show tezepelumab reduced exacerbation rates across a diverse real-world cohort, including smokers, adolescents, and patients with comorbid COPD.

HCPLive Five at Asthma Updates at ATS 2026

HCPLive Five: Asthma Updates at ATS 2026

2026 American Thoracic Society (ATS) International Conference

 in Orlando, Florida, with new data challenging long-held assumptions about who benefits from biologic therapy and how to measure that benefit.

 — Tezepelumab: 70% exacerbation reduction across phenotypes including smokers and comorbid COPD (PASSAGE).

 — Dupilumab: nearly 2x remission odds; 4x wins in "hot-hot" eosinophil/FeNO patients (QUEST win ratio analysis).

 — Tezepelumab: 2.93x greater OCS reduction vs placebo; 36% discontinued OCS entirely (SUNRISE).

 — Periconception eosinophils: each 100 cells/µL increase linked to 0.20 additional exacerbations (P <.001).

 — Depression: 2x odds of poorly controlled asthma independent of BMI, race, and socioeconomic status.

Expert interviews from ATS 2026, Orlando.

In this HCPLive Five, 5 physician experts share findings that expand the treatment conversation beyond traditional phenotypes: tezepelumab demonstrating efficacy in active smokers and patients with comorbid chronic obstructive pulmonary disease (COPD), dupilumab pushing toward remission in high-inflammation type 2 disease, and a first look at periconception eosinophils as a pregnancy risk biomarker. Rounding out the lineup, new oral corticosteroid (OCS) reduction data from phase 3 SUNRISE and an analysis on depression and asthma control underscore how much of the disease burden still goes unaddressed in routine clinical practice.

Depression Doubles Poorly Controlled Asthma Odds but Goes Unscreened

Depression and Poor Asthma Control Call for Mental Health Attention, With Brittany Duchene, MD

Depressive symptoms were associated with twice the odds of poorly controlled asthma yet showed no significant differences in exacerbation rates or spirometry, according to research presented at ATS 2026 by Brittany Duchene, MD, of the University of Vermont Medical Center. The cross-sectional analysis pooled data from three American Lung Association cohorts (n = 741) using PHQ-9 and CES-D screening tools. BMI emerged as an independent predictor of urgent healthcare utilization, with data suggesting even 5% body weight reduction improves asthma outcomes. Duchene called the depression-asthma control discordance an important and underrecognized gap warranting routine mental health screening in asthma management.

Tezepelumab Reduces Severe Asthma Exacerbations in Smokers and Comorbid COPD Patients: PASSAGE

Tezepelumab Reduced Severe Asthma Across Phenotypes in Phase 4 PASSAGE, With Njira Lugogo, MD

Tezepelumab reduced annualized asthma exacerbation rates by 70% over 52 weeks in the phase 4 PASSAGE study, with consistent reductions of 54 to 77% across phenotypes, including active smokers, patients with comorbid COPD, and those with low eosinophil counts, according to data presented at ATS 2026. Njira Lugogo, MD, director of the asthma program at the University of Michigan, highlighted that these traditionally underrepresented populations showed treatment effects comparable to the broader cohort. Patient-reported outcomes improved significantly across ACQ-6, AIRQ, and SGRQ measures. Lugogo noted the findings challenge the common clinical practice of withholding biologics from patients who have not yet stopped smoking.

Dupilumab Nearly Doubles Remission Odds in Type 2 Asthma With Elevated Eosinophils and FeNO

Dupilumab Nearly Doubled Remission Odds in Type 2 Asthma, With Simon Couillard, MD

Dupilumab nearly doubled the odds of achieving clinical remission in moderate-to-severe type 2 asthma, with patients showing both elevated eosinophils (≥ 300 cells/μL) and high FeNO (≥ 35 ppb) demonstrating 4-fold greater remission wins, according to a win ratio analysis of the phase 3 QUEST trial presented at ATS 2026. Simon Couillard, MD, of the Université de Sherbrooke, applied a hierarchical endpoint framework prioritizing exacerbation elimination, lung function, and symptom control. Couillard advocated for routine eosinophil and FeNO biomarker screening to identify optimal biologic candidates earlier and called remission an achievable, though currently treatment-dependent, target in asthma care.

Periconception Eosinophil Counts Predict Asthma Exacerbations During Pregnancy

Periconception Eosinophil Counts Predict Asthma Exacerbations in Pregnancy, With Christian Cardillo, MD

Periconception eosinophil counts were independently associated with increased asthma exacerbation frequency during pregnancy, with each 100 cells/µL increase linked to 0.20 additional exacerbations (

 <.001), according to late-breaking data presented at ATS 2026 by Christian Cardillo, MD, of Lewis Katz School of Medicine at Temple University Hospital. The single-center study of 31 pregnant patients suggests eosinophils, already part of routine CBC testing around 8–12 weeks’ gestation, could serve as a scalable biomarker for identifying high-risk type 2 inflammatory asthma phenotypes earlier in pregnancy. Cardillo called findings exploratory but noted prospective validation could support earlier pulmonology or maternal-fetal medicine referrals.

Tezepelumab Cuts Oral Corticosteroid Use by Nearly Two-Thirds in Severe OCS-Dependent Asthma: SUNRISE

Phase 3 SUNRISE: Tezepelumab Shows Meaningful OCS Reduction in Severe Asthma, With Michael E. Wechsler, MD

Phase 3 SUNRISE trial data presented at ATS 2026 showed tezepelumab-treated patients were nearly 3 times more likely to achieve meaningful oral corticosteroid (OCS) reduction versus placebo (cumulative OR 2.93; 

 =.003) in severe OCS-dependent asthma, with 36% discontinuing OCS entirely. Michael Wechsler, MD, of National Jewish Health, noted the findings align with prior SOURCE trial and real-world Wayfinder data, reinforcing tezepelumab's consistent evidence base.

Beyond OCS reduction, tezepelumab improved pre-bronchodilator FEV1 and asthma control scores. Wechsler highlighted the drug's upstream TSLP-blocking mechanism—inhibiting IL-4, IL-5, and IL-13 pathways—as key to its broad, phenotype-spanning efficacy.

Looking for more ATS 2026 coverage? Don't miss our 

HCPLive Five on late-breaking phase 3 pulmonology data 

featuring expert interviews on AD109 for OSA, ralinepag for PAH, ALIS for MAC lung disease, and more.

Editor’s note: Disclosures include GlaxoSmithKline, GENZYME CORPORATION, SANOFI-AVENTIS US, AstraZeneca Pharmaceuticals, Regeneron Pharmaceuticals, and Incyte Corporation for Lugogo; AstraZeneca Pharmaceuticals and GlaxoSmithKline for Cardillo; and SANOFI-AVENTIS US, GENZYME CORPORATION, GlaxoSmithKline, Merck Sharp & Dohme, AstraZeneca Pharmaceuticals for Wechsler. Duchene and Couillard have no reported disclosures. 

5 interviews. 5 minutes. The asthma data from ATS 2026 your patients will be asking about.