Michael Wechsler, MD, of National Jewish Health.

Michael Wechsler, MD, MSc

 who reached clinical remission with twice-yearly depemokimab (Exdensur) in year 1 had fewer exacerbations and greater lung function gains in year 2, according to an integrated analysis presented at the 

Depemokimab, an ultra-long-acting interleukin-5 (IL-5) antagonist, received FDA approval in December 2025 as add-on maintenance treatment for severe asthma with an eosinophilic phenotype in patients aged 12 years and older.² In the 52-week phase 3 SWIFT-1/-2 trials, 29% of patients receiving depemokimab achieved 4-component clinical remission at week 52, compared with 23% of patients receiving placebo.¹ The new analysis asked whether remission status at the end of year 1 carried forward into a second year of continuous treatment.

“If you can achieve remission with a specific therapy, you’re more likely to continue to stay in remission,” said Michael E. Wechsler, MD, MMSc, professor of medicine and director of The Cohen Family Asthma Institute at National Jewish Health. “It gives [us] confidence that the therapy is working and that patients will continue to do well with that therapy.”

Depemokimab Year 1 Remission Linked to Better Year 2 Asthma Outcomes

Depemokimab Clinical Remission Durability in SWIFT and AGILE

The integrated post hoc analysis included patients who received depemokimab across both the SWIFT-1/-2 trials and the 52-week AGILE open-label extension study.¹ Investigators defined 4-component clinical remission as no exacerbations across 52 weeks, no maintenance oral corticosteroid use in the final 90 days, an Asthma Control Questionnaire (ACQ)-5 score < 1.5, and a change from baseline in forced expiratory volume in 1 second (FEV1) of ≥ 0 mL.¹

Of 419 patients treated with depemokimab in both years, 405 entered the clinical remission analysis set.¹ A total of 30% (123/405) achieved clinical remission at the end of year 1, and 59% (73/123) of these patients maintained remission at the end of year 2.¹ The remaining 70% did not reach remission in year 1.¹

During year 2, the annualized exacerbation rate was 0.19 (95% CI, 0.12–0.29) among patients in remission at year 1, compared with 0.69 (95% CI, 0.57–0.82) among patients not in remission.¹ Wechsler noted patients who sustained remission into year 2 had no exacerbations, stable or improved lung function, no significant symptoms, and no steroid use for asthma.

Depemokimab Year 2 Outcomes in FEV1, ACQ-5, and SGRQ Scores


Depemokimab (Exdensur) is FDA approved as add-on maintenance treatment for severe asthma with an eosinophilic phenotype in patients aged 12 years and older, dosed by subcutaneous injection twice yearly.²


Depemokimab is an ultra-long-acting monoclonal antibody with enhanced IL-5 binding affinity and an extended half-life, which reduces eosinophilic inflammation and allows dosing every 6 months.¹

What did the SWIFT/AGILE remission analysis show?


Of patients in clinical remission at the end of year 1, 59% remained in remission at year 2, with a year 2 annualized exacerbation rate of 0.19 vs 0.69 in patients not in remission.¹

Patients achieving remission at the end of year 1 showed greater improvements across all 3 secondary outcomes at the end of year 2, measured as least squares mean change from SWIFT-1/-2 baseline.¹ St George’s Respiratory Questionnaire (SGRQ) total score improved by −23.57 points (95% CI, −26.53 to −20.62) in the remission group vs −13.15 points (95% CI, −15.13 to −11.17) in the nonremission group.¹

ACQ-5 score changed by −1.34 (95% CI, −1.51 to −1.17) in patients with year 1 remission vs −0.71 (95% CI, −0.82 to −0.60) in patients without remission.¹ Pre-bronchodilator FEV1 improved by 379 mL (95% CI, 301–458) vs 85 mL (95% CI, 33–137), respectively.¹ The trend remained consistent at every assessed timepoint during year 2.¹

Wechsler emphasized the 70% of patients not meeting the 4-component definition in year 1 may still benefit from continued treatment. He described remission as a high bar and noted ongoing debate among experts on which components and what duration should define it.

“Not everyone’s going to achieve remission, but they might still have benefits,” Wechsler said. “They might have benefits in terms of reduction in steroid dose, reduction in exacerbations, improvement in lung function, [and] improvement in symptoms.”

He added a 3-component definition without a lung function criterion may better fit patients with a near-normal baseline FEV1, for whom eliminating prior exacerbations is the more meaningful outcome.

“Sometimes some people start off [with] a high lung function,” he said. “If their FEV1 is 85%, they may not necessarily improve in terms of lung function. Whereas if they had two exacerbations in the year prior, that is important.”

Editor’s note: Reported disclosures for Wechsler include GENZYME CORPORATION, GlaxoSmithKline, Regeneron Healthcare Solutions, and more.

Wechsler ME, Tacon CE, Muccino D, et al. Attainment of clinical remission with twice-yearly depemokimab in year 1 is associated with improved clinical outcomes in year 2: SWIFT/AGILE integrated analysis. Presented at: CHEST 2026; October 20, 2026; Phoenix, AZ.

GSK. Exdensur (depemokimab) approved by US FDA for the treatment of severe asthma. Published December 16, 2025. Accessed October 21, 2026. 

https://www.businesswire.com/news/home/20251216764904/en/Exdensur-depemokimab-approved-by-US-FDA-for-the-treatment-of-severe-asthma

Videos

Michael Wechsler, MD, reports 59% of patients in clinical remission with twice-yearly depemokimab at year 1 maintained it at year 2 in SWIFT/AGILE.

This episode, "Tapering Inhalers and Initiating Biologics Earlier in Severe Asthma," features the panel closing on two unresolved practical questions.

Tapering Inhalers and Initiating Biologics Earlier in Severe Asthma

Dr. Chupp asks Dr. Hanania whether he tapers inhalers in patients on biologics, noting the SHAMAL results were dramatic but ran under a year, that most remission data are observational, and that controlled studies suggest perhaps 20% reduce inhaled steroids versus controls. Dr. Hanania says patients announcing they stopped their inhalers freaks him out, partly because insurers want documented inhaler compliance. He reduces the dose but does not stop inhaled steroids completely, noting SHAMAL met its primary endpoint but raised lung function concerns in those who came off entirely, over a period he considered too short. He will not extrapolate across agents with different mechanisms, and awaits ongoing studies. Oral steroids, by contrast, should already be gone. He does not space biologics, though patients ration doses on their own for co-pay reasons, and he awaits the studies Dr. Wechsler and another colleague are pursuing.

Dr. Chupp closes on initiation. Trials enrolled patients on high-dose ICS-LABA who were exacerbating, so the agents are seen as exacerbation-reducers. He asks whether the panel waits for exacerbations, and whether approval becomes difficult otherwise. Dr. Wechsler primarily treats exacerbation-prone patients but will use a biologic for significant symptoms, decrement in lung function, or oral steroid dependence, and finds a symptomatic patient on triple therapy who cannot live fully is usually approvable despite pushback.

Dr. Ross agrees, describing patients who are clinical but do not fit the insurer's box: up all night scratching with atopic dermatitis, or symptomatic with subclinical polyps. Her prescription is documentation. Gather every biomarker and objective measure, including post-bronchodilator FEV1 showing reversibility on appropriate therapy, submit it, and keep appealing. Dr. Chupp thanks the panel and the audience.

Thank you for watching this HCPLive Peer Exchange series on severe asthma and upper airway disease. Please subscribe to our eNewsletter for information on upcoming video series.

Patients taper their own inhalers, and payers approve on exacerbations alone. The panel closes on where the evidence runs out and where documentation and advocacy take over.

In "Selecting a Biologic in Severe Asthma: Biomarkers, Comorbidities, and Payers," our experts turn to the decision every clinician faces once the diagnosis is settled.

Selecting a Biologic in Severe Asthma: Biomarkers, Comorbidities, and Payers

Dr. Chupp asks Dr. Hanania whether anti-TSLP availability has shifted him toward using an anti-alarmin first, given trial data showing efficacy across the spectrum without requiring a biomarker, and whether he considers combination therapy or overlapping agents when switching. Dr. Hanania says the choice remains multifactorial. For an oral steroid-dependent patient with no high eosinophils and no elevated FeNO, anti-IL-4 receptor therapy would be his choice, though emerging anti-TSLP data in that group are being presented.

Otherwise, he reads the biomarker profile and the comorbidities. Atopic dermatitis with severe asthma leaves only one approved option. Polyposis leaves several. For severe asthma with low biomarkers, anti-TSLP is the only agent that targets non-type 2 disease. For very high eosinophils above 1,500 with polyposis he may choose an anti-IL-5, though anti-TSLP might also work. Patient preference and payer coverage matter just as much: some patients refuse injections every two weeks but accept monthly, every two months, or the twice-yearly agent, which is approved only in eosinophilic asthma.

On assessment, he tells patients to be patient with him. This is not one injection and a verdict; he waits three to four months, unless side effects intervene. Exacerbations are hard to judge over three months, so he assesses how the patient feels. If nothing changes and exacerbations continue, he returns to biomarkers and phenotyping to choose the next agent.

Asked about two biologics at once, he says he does not, though colleagues have obtained reimbursement for it. He expects bispecific and tri-specific agents to change that soon. He asks Dr. Wechsler the question patients ask him constantly: once remission is reached, is this treatment for life?

Dr. Wechsler lays out the options a patient in remission faces. The default is continuing both the biologic and background therapy. Most patients feel so well they see no reason to change. But some want to reduce cost or exposure.

The second option is cutting back the background inhaled steroids. He cites the SHAMAL study with anti-IL-5 receptor therapy in well-controlled patients, notes ongoing anti-TSLP tapering studies, and adds that real-world data show many patients taper background therapy and do well.

The third is stopping the biologic and continuing background inhalers. Real-world data argue against it: exacerbations increase rapidly in about 50% of patients. The fourth, which his group is studying, is continuing both while extending the dosing interval, from every two weeks to four, or four to six or eight. Because these are largely long-acting drugs, control may hold, and the cost to society would fall. Data in chronic sinusitis with nasal polyps suggest it can be done safely; the equivalent asthma study is still needed.

In "Tapering Inhalers and Initiating Biologics Earlier in Severe Asthma," the panel will close on tapering and the fight to start earlier.

With an anti-alarmin option that does not require a biomarker, selection could have become simpler. Dr. Hanania explains why it stays multifactorial, and why he waits before judging response.

This episode, "Remission in Severe Asthma: Aligning Physician Goals with Patient Goals," features the panel setting the practical issues aside to ask what success looks like.

Remission in Severe Asthma: Aligning Physician Goals with Patient Goals

Dr. Chupp reframes the discussion around the patient. The goal is no longer stopping exacerbations; it is remission. He imagines patients on an injection monthly or every six months with only a rescue inhaler, rather than stacking inhaled therapies plus a biologic just to avoid prednisone twice a year. The obstacle is insurance and the absence of randomized data, though observational and retrospective data support it.

Dr. Ross describes triage: allergists control the most life-threatening problem first, and severe asthma still carries mortality risk. Once that fire is out, the prevention work begins with allergen immunotherapy and household control measures. She then makes a pointed argument about case-finding. GINA reserves biologics for severe asthmatics, but she believes severe patients are being missed and put in the wrong bucket. They go to urgent care and cannot get in with a physician. History-taking is long, but it identifies the patient with an FEV1 of 85 who visited urgent care four times last year and is oral steroid-dependent. That patient is high risk and is not being reported.

She also cites data that controlling atopic dermatitis calms the type 2 cascade and improves both asthma and allergic rhinitis, supporting treatment of the whole systemic condition.

Asked about switching, Dr. Ross says remission is the goal for everybody, but it requires shared decision-making. Physicians set goals like no exacerbations and staying out of hospital. Patients want to play with their kids, sleep well, or visit an amusement park without shortness of breath. When a clinician calls a patient controlled and the patient disagrees, she switches the biologic. Emerging agents targeting TSLP and IL-13, or IL-4, IL-5, and IL-13, plus ultra-long-acting options, make her optimistic.

Up next, in "Selecting a Biologic in Severe Asthma: Biomarkers, Comorbidities, and Payers," Dr. Hanania explains how he chooses among them.

Clinicians define control as no exacerbations and no hospital stays. Dr. Ross argues patients define it differently, and that the gap between the two should drive treatment decisions.

Michael Wechsler, MD, MSc

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