Drug Update · Pulmonology

Mepolizumab: Severe Asthma Rate Ratio 0.47 (MENSA)

July 20, 2026

MENSA rate ratio

0.47 (0.35, 0.64)

MENSA exacerbations per year NUCALA vs placebo

0.83 vs 1.74

DREAM rate ratio

0.52 (0.39, 0.69)

NUCALA dose severe asthma (≥12 years)

100 mg SC every 4 weeks

Tezspire administration

210 mg subcutaneously once every four weeks

Clinical Perspective

Pulmonologists and clinicians working in specialized severe asthma clinics should assess phenotype (T2-high versus T2-low) and comorbidities when considering biologic therapy, per expert review recommendations ^[1]. The NUCALA clinical program supports use of mepolizumab in patients with an eosinophilic phenotype to reduce exacerbation frequency as summarized in the prescribing information and trials MENSA and DREAM ^[3]. Which biologic provides the optimal balance of exacerbation reduction, steroid-sparing effect, dosing frequency, and applicability across phenotypes for individual patients remains to be defined by comparative studies and longer-term data in specialized clinics?

Dr. Nikhil Chatterjee · Pulmonology

Mepolizumab (NUCALA) remains a key biologic for severe eosinophilic asthma after randomized trials showed lower exacerbation rates compared with placebo; MENSA reported exacerbations per year 0.83 with NUCALA versus 1.74 with placebo (rate ratio 0.47; 95% CI 0.35-0.64) ^[3]. Tezepelumab (Tezspire) is FDA-approved as an add-on maintenance treatment for severe asthma for patients aged 12 years and older and targets thymic stromal lymphopoietin (TSLP) ^[2]. PubMed review data list available biologics and emerging agents including depemokimab and ongoing trials in 2025 ^[1].

Clinical Context

Current biologic options for severe asthma include omalizumab (anti-IgE), mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5 receptor), dupilumab (anti-IL-4/IL-13), and tezepelumab (anti-TSLP) as described in a 2025 review ^[1]. The review emphasizes verification of inhaler technique, correction of modifiable risk factors, phenotyping as T2-high or T2-low, and referral to specialized severe asthma clinics for management and biologic selection ^[1]. Outcomes to evaluate when selecting a biologic include reductions in systemic corticosteroid use, exacerbations and healthcare use, and improvements in symptoms and lung function ^[1]. Dupilumab, mepolizumab, and omalizumab are noted as also approved for chronic rhinosinusitis with nasal polyps (CRSwNP) ^[1]. Depemokimab is described as an ultra-long-acting anti-IL-5 with phase III results reported as a twice-yearly dosing strategy in 2025-level summaries ^[1]. Tezspire is identified as the first treatment targeting TSLP and is approved without limitation to a single severe asthma phenotype ^[2].

Key Findings

The MENSA trial showed NUCALA 100 mg subcutaneously reduced the annual rate of exacerbations: 0.83 exacerbations per year with NUCALA versus 1.74 with placebo (rate ratio 0.47; 95% CI 0.35-0.64) ^[3].
Clinicians should consult current prescribing information for full dosing guidance.
The DREAM trial (dose-ranging and exacerbation trial) reported exacerbations per year 1.24 with mepolizumab 75 mg IV versus 2.40 with placebo (rate ratio 0.52; 95% CI 0.39-0.69) ^[3].
In MENSA and DREAM, treatment with mepolizumab was associated with fewer exacerbations requiring hospitalization and/or emergency department visits compared with placebo per the prescribing information ^[3].
The SIRIUS trial assessed oral corticosteroid (OCS) reduction and enrolled patients requiring daily OCS; baseline mean OCS use was 13.2 mg in the placebo group and 12.4 mg in the NUCALA 100 mg group in that trial cohort ^[3].
Tezspire (tezepelumab-ekko) demonstrated significant reductions in the annualized rate of asthma attacks versus placebo in two clinical trials and was approved as an add-on maintenance treatment for patients aged 12 years and older with severe asthma ^[2].

Safety & Tolerability

Tezspire should not be used to treat short-term asthma symptoms or short-term asthma attacks ^[2].
Patients should not discontinue systemic or inhaled corticosteroid treatments abruptly after starting Tezspire; dose reductions should be gradual and supervised by a health care professional ^[2].
Patients with pre-existing helminth infections should be treated for the helminth infection before starting Tezspire for asthma ^[2].
Patients with a serious hypersensitivity reaction to Tezspire must not take Tezspire ^[2].
Live vaccines should be avoided in patients receiving Tezspire ^[2].
Monitoring of patients after administration of biologic agents is recommended and preparation/administration instructions are provided in the NUCALA prescribing information ^[3].

Study Design

The NUCALA clinical program included DREAM (a 52-week dose-ranging and exacerbation trial), MENSA (a 32-week placebo- and active-controlled trial), and SIRIUS (a 24-week OCS-reduction trial) in patients with severe asthma; MENSA and SIRIUS required blood eosinophil criteria for enrollment in the confirmatory trials and assessed exacerbation frequency and OCS reduction ^[3]. Tezspire approval was supported by two clinical trials in which participants received tezepelumab 210 mg or placebo subcutaneously once every four weeks for 52 weeks (NCT02054130 and NCT03347279 noted in the FDA summary) ^[2]. Clinicians should consult current prescribing information for full dosing guidance. Further trial identifiers and additional study details were cited in the prescribing information and FDA review documents ^[2]^[3].

FAQ

Q1 What is mepolizumab (NUCALA) approved for?

NUCALA is indicated as add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma with an eosinophilic phenotype. NUCALA is also indicated for add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adults, for add-on maintenance treatment of adult patients with inadequately controlled COPD and an eosinophilic phenotype, for treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), and for treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) of ≥6 months without an identifiable non-hematologic secondary cause.

Q2 How does mepolizumab work?

Mepolizumab is an interleukin-5 (IL-5) antagonist monoclonal antibody (IgG1 kappa). It binds to IL-5 with a dissociation constant of 100 pM and inhibits IL-5 bioactivity by blocking its binding to the alpha chain of the IL-5 receptor complex on eosinophils, thereby reducing production and survival of eosinophils; the mechanism of action in asthma and other indicated conditions has not been definitively established in the prescribing information.

Q3 What is the recommended dose of mepolizumab (NUCALA)?

For severe asthma in patients aged 12 years and older the recommended dose is 100 mg administered subcutaneously once every 4 weeks; for patients aged 6 to 11 years the recommended dose is 40 mg subcutaneously once every 4 weeks. Other indicated conditions have different recommended doses (for example, 300 mg subcutaneously every 4 weeks for EGPA and HES in adults). NUCALA is for subcutaneous use only and the prescribing information provides preparation and administration instructions. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the side effects of mepolizumab (NUCALA)?

[Information] was not available in the provided source excerpts.

Clinicians should consult current prescribing information for complete dosing guidance.

Mepolizumab: Severe Asthma Rate Ratio 0.47 (MENSA)

Mepolizumab: Severe Asthma Rate Ratio 0.47 (MENSA)

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

Get weekly clinical updates for Pulmonology in your inbox.

Related Clinical Updates

FDA Approves depemokimab for Severe Eosinophilic Asthma: Rate Ratio 0.42

dupilumab: FDA Approves for COPD; FEV1 Improved 0.09 L in BOREAS

FDA Approves Tezepelumab for Severe Asthma: Rate Ratio 0.44 in NAVIGATOR

Verified HCP Portal