Tezspire (Tezepelumab)
tezepelumab-ekko — first-in-class anti-TSLP human monoclonal antibody (IgG2λ)
Indications
Tezepelumab is the first and only biologic that targets thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine that sits upstream of multiple inflammatory cascades. Unlike anti-IL-5 or anti-IL-4Rα agents that target downstream mediators, tezepelumab blocks inflammation at its source in the airway epithelium, conferring efficacy across asthma phenotypes regardless of baseline eosinophil count or allergic status.
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Severe asthma | ≥12 years | Add-on maintenance | FDA Approved |
| Chronic rhinosinusitis with nasal polyps (CRSwNP) | ≥12 years | Add-on maintenance | FDA Approved |
Tezepelumab is not indicated for acute bronchospasm or status asthmaticus. It is a maintenance therapy and must not replace rescue inhalers. Notably, the pivotal trials enrolled patients across all inflammatory phenotypes without requiring a minimum baseline eosinophil count, distinguishing tezepelumab from other asthma biologics.
COPD (eosinophilic phenotype) — Phase 2a COURSE trial (using 420 mg Q4W, double the approved asthma dose) showed a 37% exacerbation reduction in patients with baseline blood eosinophils ≥150 cells/µL (overall population: 17%, not statistically significant). FDA breakthrough therapy designation granted. Phase 3 trial ongoing. Evidence quality: moderate.
Eosinophilic esophagitis (EoE) — Phase 3 CROSSING trial ongoing; FDA Orphan Drug Designation granted October 2021. Evidence quality: low (no phase 3 results yet).
Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Severe asthma — add-on maintenance (≥12 years) | 210 mg SC | 210 mg Q4W | 210 mg Q4W | No loading dose required; flat dose regardless of body weight Continue all background asthma controllers |
| CRSwNP — inadequately controlled (≥12 years) | 210 mg SC | 210 mg Q4W | 210 mg Q4W | No loading dose; same dose as asthma Continue nasal corticosteroids as standard of care |
| Severe asthma — OCS-sparing intent | 210 mg SC | 210 mg Q4W | 210 mg Q4W | The OCS-sparing trial did not meet its primary endpoint Taper OCS gradually under physician supervision if appropriate; do not rely on tezepelumab alone for OCS reduction |
Tezepelumab uses a single fixed dose of 210 mg every 4 weeks for all indications, all ages ≥12 years, and all body weights. There is no loading dose, no weight-based titration, and no indication-specific regimen variation. This is among the simplest dosing schemes of any asthma biologic. If a dose is missed, administer it as soon as possible and resume the usual schedule. If the next dose is already due, administer it as planned.
Tezepelumab is available as a single-dose vial, pre-filled syringe, and pre-filled pen, all containing 210 mg/1.91 mL. The vial and pre-filled syringe are intended for healthcare provider administration. The pre-filled pen may be self-administered by patients or caregivers after proper training. Allow to reach room temperature (~60 minutes) before injection. Inject into thigh, abdomen, or upper arm (caregiver only for upper arm). Rotate injection sites. Store refrigerated; once at room temperature, use within 30 days.
Pharmacology
Mechanism of Action
Tezepelumab is a human monoclonal antibody (IgG2λ) that binds to thymic stromal lymphopoietin (TSLP) with high affinity (Kd ~15.8 pM), preventing its interaction with the heterodimeric TSLP receptor on the surface of immune cells. TSLP is an epithelial-derived alarmin cytokine released from airway and mucosal epithelial cells in response to environmental triggers such as allergens, viruses, pollutants, and bacteria. It occupies a uniquely upstream position in the inflammatory cascade, activating dendritic cells, mast cells, type 2 innate lymphoid cells (ILC2s), eosinophils, and T lymphocytes. By neutralizing TSLP before it initiates downstream signalling, tezepelumab suppresses multiple inflammatory pathways simultaneously, reducing blood eosinophils, fractional exhaled nitric oxide (FeNO), serum IgE, IL-5, and IL-13. This broad upstream blockade explains why tezepelumab reduces asthma exacerbations across eosinophilic, allergic, and non-eosinophilic phenotypes, a distinguishing feature among asthma biologics. In CRSwNP, increased TSLP expression in nasal polyp tissue drives mucosal inflammation, and blocking TSLP reduces polyp burden, nasal congestion, and the need for surgery or systemic corticosteroids.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Bioavailability ~77%; Tmax 3–10 days (SC); dose-proportional PK over 0.01–2× recommended dose; no clinically relevant differences by injection site | Monthly dosing achieves steady state at ~12 weeks; accumulation ratio ~1.86-fold at Ctrough; no loading dose needed |
| Distribution | Vc 3.9 L; Vp 2.2 L (70 kg individual); largely confined to vascular and interstitial compartments | Low Vd typical of monoclonal antibodies; higher body weight lowers exposure but has no meaningful impact on efficacy or safety, so no weight-based dosing is required |
| Metabolism | Intracellular catabolism by proteolytic enzymes widely distributed in the body; not metabolized by hepatic CYP enzymes | No hepatic dose adjustment required; no traditional drug–drug interactions via CYP pathways expected |
| Elimination | Clearance ~0.17 L/day (70 kg); t½ ~26 days; no evidence of target-mediated clearance within the studied dose range | Linear elimination kinetics simplify dosing; no renal dose adjustment required (similar clearance in mild-moderate renal impairment vs normal function); not studied in severe renal impairment |
Side Effects
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nasopharyngitis | 18% vs 10% placebo | Most common adverse reaction in the WAYPOINT CRSwNP trial; generally mild and self-limiting; not elevated above placebo in asthma trials |
| Upper respiratory tract infection | 12% vs 8% placebo | Includes viral and bacterial URTI; typical of biologic-treated populations in long-duration trials; no increased serious infection risk |
| Adverse Effect | Incidence (Asthma / CRSwNP) | Clinical Note |
|---|---|---|
| Pharyngitis | 4% / 5% vs 3% / 1% placebo | Includes streptococcal and viral pharyngitis; consistent across both indications |
| Arthralgia | 4% / 3% vs 3% / 2% placebo | Mild musculoskeletal complaints; no association with autoimmune arthritis reported |
| Back pain | 4% / 5% vs 3% / 2% placebo | Non-specific; rates only marginally above placebo |
| Epistaxis | — / 6% vs — / 3% placebo | CRSwNP-specific; likely related to underlying nasal polyp disease and intranasal corticosteroid use |
| Influenza | — / 4% vs — / 1% placebo | CRSwNP trial only (WAYPOINT, 52-week duration) |
| Injection site reactions | 3.3% / 4% vs 2.7% / 2% placebo | Erythema, swelling, pain; generally mild; rate higher with pre-filled pen (5.7%) vs syringe (0%) in open-label trial, though not designed for direct comparison |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Anaphylaxis | Rare (postmarketing) | Minutes to hours; some cases with delayed onset (days) | Emergency treatment; weigh risks vs benefits before continuing; permanent discontinuation may be needed |
| Hypersensitivity reactions (rash, allergic conjunctivitis) | Uncommon (<3%) | Hours to days after injection | Consider benefits vs risks for individual patient; may continue with monitoring or discontinue |
| Serious cardiac adverse events | IR 1.08 per 100 PY vs 0.21 placebo | Variable (observed in DESTINATION extension, up to 104 weeks) | Events were heterogeneous; adjudicated MACE not significantly different (IR 0.60 vs 0.42 per 100 PY); clinical relevance remains under evaluation; monitor patients with pre-existing cardiovascular risk factors |
| Helminth infection (theoretical risk) | Unknown | Any time during treatment | Treat pre-existing infections before initiating; if infection occurs and does not respond to anti-helminth treatment, discontinue tezepelumab until resolved |
In the long-term extension trial (up to 104 weeks), the incidence rate of serious cardiac adverse events was numerically higher with tezepelumab (IR 1.08 per 100 PY) versus placebo (IR 0.21 per 100 PY). However, the events were heterogeneous in type, and the rate of adjudicated MACE (cardiovascular death, non-fatal MI, non-fatal stroke) was not significantly different between groups (IR 0.60 vs 0.42). This signal warrants continued monitoring, particularly in patients with pre-existing cardiovascular disease, but has not led to a labelled contraindication or boxed warning.
Drug Interactions
No formal drug interaction studies have been conducted with tezepelumab. As a monoclonal antibody degraded by proteolysis, it is not metabolized by hepatic CYP enzymes and is not expected to affect the pharmacokinetics of co-administered drugs. Population pharmacokinetic analysis confirmed that commonly co-administered asthma medications (leukotriene receptor antagonists, theophylline/aminophylline, oral and inhaled corticosteroids) had no clinically meaningful effect on tezepelumab clearance.
Monitoring
-
Asthma Control
Weeks 12–16 initial; then Q3–6 months
Routine Assess exacerbation frequency, ACQ-6, FEV1, and overall symptom control. Clinical response typically becomes evident within 4–8 weeks. If no improvement by 16–24 weeks, reassess treatment strategy. -
CRSwNP Response
Weeks 12–24; then Q6 months
Routine Evaluate nasal polyp score, nasal congestion score, and sense of smell. In WAYPOINT, improvements were seen as early as 4 weeks and sustained through 52 weeks. Consider endoscopic assessment at 6–12 months. -
Hypersensitivity
Each administration
Routine Observe for signs of hypersensitivity (rash, urticaria, conjunctivitis, angioedema) during and after each injection. Postmarketing anaphylaxis has been reported; some cases with delayed onset (days). Consider monitoring for 30 minutes after the first few doses in a clinical setting. -
Cardiovascular Risk
Baseline; then clinically guided
Trigger-based A numerical imbalance in serious cardiac AEs was observed in the DESTINATION extension trial (IR 1.08 vs 0.21 per 100 PY). Adjudicated MACE was not significantly different. Be alert to cardiac symptoms in patients with pre-existing cardiovascular disease. -
Helminth Screening
Baseline (endemic areas)
Routine Treat pre-existing infections before starting therapy. TSLP may be involved in anti-helminth immunity; if infection occurs during treatment and does not respond to treatment, discontinue tezepelumab until resolved. -
Vaccination Status
Baseline
Routine Complete age-appropriate vaccinations before initiating tezepelumab. Avoid live attenuated vaccines during treatment. Inactivated vaccines (influenza, COVID-19, pneumococcal) may be given concurrently. -
Biomarkers
Baseline; optional during treatment
Trigger-based Blood eosinophils, FeNO, and serum IgE decrease during tezepelumab treatment. These reductions confirm pharmacodynamic activity but should not be used alone to guide treatment decisions. Note: tezepelumab efficacy is not dependent on baseline eosinophil count.
Contraindications & Cautions
Absolute Contraindications
- Known hypersensitivity to tezepelumab-ekko or any excipient — includes any prior anaphylaxis, serum sickness, or severe allergic reaction to a tezepelumab dose.
Relative Contraindications (Specialist Input Recommended)
- Active helminth infection — TSLP may be involved in the immunological response to helminth infections. Patients with known infections were excluded from clinical trials. Treat infection completely before initiating therapy.
- Planned administration of live attenuated vaccines — safety and efficacy of live vaccines during tezepelumab treatment have not been evaluated. Complete live vaccinations before starting therapy.
Use with Caution
- Pre-existing cardiovascular disease — a numerical imbalance in serious cardiac AEs was seen in the DESTINATION extension trial. While MACE rates were not significantly different, vigilance is warranted in patients with established cardiac risk factors.
- Oral corticosteroid-dependent patients — do not abruptly discontinue systemic or inhaled corticosteroids when starting tezepelumab. The OCS-sparing trial did not meet its primary endpoint; gradual tapering under medical supervision is still appropriate but should not be assumed to succeed.
- Pregnancy and lactation — no human data available. As an IgG2 antibody, tezepelumab is expected to cross the placenta, particularly in the third trimester. Animal studies showed no fetal harm. Present in cynomolgus monkey milk at up to 0.5% of maternal serum concentrations. Weigh benefits versus risks.
- Geriatric patients — no overall differences in safety or efficacy were observed in patients ≥65 years (18% of asthma cohort; 14% of CRSwNP cohort). No dose adjustment needed.
- Pediatric patients <12 years — safety and efficacy have not been established.
Tezepelumab does not carry an FDA Boxed Warning. However, the PI includes cardiovascular safety data from the DESTINATION extension trial showing a higher incidence rate of serious cardiac adverse events versus placebo (IRD 0.88 per 100 PY; 95% CI: 0.24, 1.53). The types of events were heterogeneous, and adjudicated MACE was not significantly different. Clinicians should be aware of this signal, particularly when treating patients with cardiovascular comorbidities.
Patient Counselling
Purpose of Therapy
Tezepelumab is a biologic medicine that targets TSLP, one of the earliest signals that triggers inflammation in your airways. By blocking TSLP, it helps reduce asthma attacks or nasal polyp symptoms from multiple causes at once. It is designed to work as a long-term maintenance treatment alongside your existing inhalers and medications, not as a replacement for rescue inhalers or acute treatments.
How to Take
Tezepelumab is given as a single injection under the skin once every 4 weeks. The same dose (210 mg) is used for everyone regardless of weight. It can be administered by a healthcare provider using a vial or pre-filled syringe, or self-injected at home using the pre-filled pen after proper training. Store it in the refrigerator. Before injection, let it warm to room temperature for about 60 minutes. Inject into the thigh or stomach (avoiding the area around the navel). A caregiver can also inject into the upper arm. Rotate sites with each injection.
Sources
- Tezspire (tezepelumab-ekko) injection, for subcutaneous use. Full Prescribing Information. Amgen Inc. / AstraZeneca Pharmaceuticals LP. Revised 10/2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761224s006lbl.pdf Primary source for all dosing, indications, adverse reactions, warnings, pharmacokinetic data, and clinical trial results in this monograph.
- FDA approval announcement: Tezspire for CRSwNP. Amgen press release, October 17, 2025. https://www.amgen.com/newsroom/press-releases/2025/10/fda-approves-tezspire-for-chronic-rhinosinusitis-with-nasal-polyps Announcement of second FDA indication (CRSwNP); includes WAYPOINT efficacy summary.
- Corren J, Parnes JR, Wang L, et al. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377:936-946. doi:10.1056/NEJMoa1704064 PATHWAY phase 2b dose-ranging trial establishing proof of concept and the 210 mg Q4W dose; source for early safety and exacerbation data.
- Menzies-Gow A, Corren J, Bourdin A, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med. 2021;384:1800-1809. doi:10.1056/NEJMoa2034975 NAVIGATOR pivotal phase 3 trial; primary source for exacerbation rate reduction (56%), FEV1 improvement, and safety data supporting FDA approval in severe asthma.
- Menzies-Gow A, Bourdin A, Chupp G, et al. Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study. Lancet Respir Med. 2023;11:425-438. doi:10.1016/S2213-2600(22)00487-8 DESTINATION long-term extension trial (up to 104 weeks); source for cardiovascular safety signal data and sustained efficacy.
- Han JK, Bachert C, Desrosiers M, et al. Tezepelumab for chronic rhinosinusitis with nasal polyps. N Engl J Med. 2025. Published simultaneously with WAYPOINT trial presentation at AAAAI/WAO 2025. doi:10.1056/NEJMoa2414861 WAYPOINT phase 3 trial for CRSwNP; demonstrated significant reductions in nasal polyp score, nasal congestion, and near-elimination of surgery need vs placebo over 52 weeks.
- Singh D, Brightling CE, Gaga M, et al. Efficacy and safety of tezepelumab versus placebo in adults with moderate to very severe COPD (COURSE): a randomised, placebo-controlled, phase 2a trial. Lancet Respir Med. 2025;13:47-58. doi:10.1016/S2213-2600(24)00324-2 Phase 2a COPD trial (420 mg Q4W); overall exacerbation reduction not significant (17%), but 37% reduction in BEC ≥150 subgroup; basis for FDA breakthrough designation and ongoing phase 3 program.
- Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2024 update. https://ginasthma.org/gina-reports/ International guideline positioning anti-TSLP therapy among biologic options for severe asthma at GINA Step 5.
- Gauvreau GM, Sehmi R, Ambrose CS, et al. Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma. Expert Opin Ther Targets. 2020;24(8):777-792. doi:10.1080/14728222.2020.1783242 Comprehensive review of TSLP biology, its role in asthma pathogenesis, and the scientific rationale for anti-TSLP therapy.
- Porsbjerg CM, Sverrild A, Lloyd CM, et al. Anti-alarmins in asthma: targeting the airway epithelium with next-generation biologics. Eur Respir J. 2020;56(1):2000260. doi:10.1183/13993003.00260-2020 Positions tezepelumab within the broader class of anti-alarmin therapies and explains the upstream epithelial targeting strategy.
- Panettieri R Jr, Lugogo N, Corren J, Ambrose CS. Tezepelumab for severe asthma: one drug targeting multiple disease pathways and patient types. J Asthma Allergy. 2024;17:219-236. doi:10.2147/JAA.S410463 Comprehensive review of tezepelumab pharmacology, clinical efficacy across phenotypes, pharmacokinetics, and immunogenicity data.
- Corren J, Menzies-Gow A, Chupp G, et al. Efficacy of tezepelumab in severe, uncontrolled asthma: pooled analysis of the PATHWAY and NAVIGATOR clinical trials. Am J Respir Crit Care Med. 2023;208(1):13-24. doi:10.1164/rccm.202210-2005OC Pooled analysis across biomarker subgroups confirming efficacy irrespective of baseline eosinophils, IgE, or FeNO.