Asthma
Johanna Taylor Katroscik, PharmD
In December 2021, FDA approved tezepelumab-ekko (Tezspire– Amgen Inc. and AstraZeneca), a first-in-class medication indicated for patients with severe asthma. It is the most recent biologic to gain FDA approval for use in asthma and is the first biologic treatment that has been approved for all types of severe asthma.
Recommended dosage and how it works
Tezspire is indicated for use in patients who are at least 12 years old with severe asthma as an add-on to their maintenance therapy. The dose for all patients is 210 mg (1.91 mL) and is administered as a single, subcutaneous injection once every 4 weeks.
Tezspire is a solution that is supplied in both a single-dose vial as well as a single-dose prefilled syringe and should be administered by a health care provider in a health care setting.
The solution should be stored in its original packaging in the refrigerator (36 °F–46 °F) and taken out approximately 60 minutes prior to administration to be brought to room temperature. Once the medication has been brought to room temperature, it must be used within 30 days and cannot be refrigerated again.
Tezspire is a monoclonal antibody that works by targeting and binding to thymic stromal lymphopoietin (TSLP), a cytokine involved in the inflammatory pathway of asthma. Once bound, it prevents TSLP from binding to and activating the TSLP receptor. Researchers hypothesize that by inhibiting TSLP receptor activation numerous other downstream inflammatory effects are also prevented.
Quick definitions
Antibody: Protein produced by the immune system in response to recognition of a harmful substance (i.e., antigen). When the immune system recognizes the harmful substance, antibodies will then work to neutralize it.
Antigen: Large molecules or proteins that induce an immune response—often attached to the surface of fungi, bacteria, or viruses.
Monoclonal antibody: Antibody produced in a lab by cloning a single cell or cell line to target a specific antigen.
Clinical trial highlights
Approval for Tezspire was based on the PATHWAY (phase 2, randomized, double-blind, placebo-controlled) and NAVIGATOR (phase 3, randomized, double-blind, placebo-controlled) trials.
The NAVIGATOR trial enrolled 1,061 participants (aged 12–80 years) who were randomized in a 1:1 ratio to receive either 210 mg tezepelumab-ekko or placebo as subcutaneous injections every 4 weeks for 52 weeks. Key inclusion criteria were that participants must have had physician-documented asthma for at least 12 months prior to trial enrollment, physician-prescribed asthma controller medication with medium- or high-dose inhaled corticosteroid (ICS) for at least 12 months, documented treatment with medium- or high-dose ICS for at least 3 months, and at least one additional maintenance asthma controller medication.
Key exclusion criteria included history of pulmonary diseases other than asthma, history of cancer, history of a clinically significant infection, current smoker or a smoking history greater than or equal to 10 pack-years, or a history of chronic alcohol or drug abuse within the 12 months leading up to the trial.
The primary endpoints of the trial were annual asthma exacerbation rate in patients with uncontrolled asthma and annual asthma exacerbation rate in patients with uncontrolled asthma whose baseline eosinophil count was less than 300 cells/microliter.
Researchers also looked at a number of secondary outcomes including changes in Asthma Control Questionnaire-6 scores, amount of time until an asthma exacerbation occurred, and change in daily rescue medication use. Results of the trial showed a clinically significant reduction in annualized asthma exacerbations as well as reduced number of emergency room visits and hospitalizations in participants who received Tezspire compared to those who received placebo.
Patient counseling
Tezspire may be an optional add-on therapy for patients with severe asthma that is not well-controlled with other medications. It is administered by a health care provider as a subcutaneous injection once every 4 weeks.
The most commonly reported adverse effects are sore throat and joint pain. Tezspire works by altering part of the immune system’s function. Patients should be counseled to avoid any live attenuated vaccines while being treated with Tezspire.
Additionally, if a patient develops a helminth infection, treatment should be discontinued until the infection has been completely treated. ■
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Other monoclonal antibodies used for asthma and their specific targets
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FDA-approved biologics for asthma (as of publication)
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Asthma indication(s)
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Mechanism of action (target)
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Dosage and administration
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Tezepelumab (Tezspire)
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Add-on maintenance treatment for severe asthma (12 years and older)
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Thymic stromal lymphopoietin inhibitor
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• 210 mg/1.91 mL administered subcutaneously once every 4 weeks.
• Must be reconstituted and administered by a health care provider.
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Omalizumab
(Xolair)
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Add-on maintenance therapy for moderate persistent asthma (6 years and older). Must have positive skin test or in
vitro reactivity to a perennial aeroallergen
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Anti-IgE
antibody
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• 75 mg to 375 mg administered subcutaneously once every 2 or 4 weeks—dose and frequency are dependent on pretreatment levels of IgE as well as body weight.
• Initial dose(s) should be administered in a health care setting.
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Mepolizumab
(Nucala)
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Add-on maintenance therapy for severe asthma with an eosinophilic phenotype (6 years and older)
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Interleukin-5
(IL-5) antagonist
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• Patients aged 6 to 11 years: 40 mg administered subcutaneously once every 4 weeks.
• Patients 12 years and older: 100 mg administered subcutaneously every 4 weeks.
• Must be reconstituted and administered by health care provider.
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Reslizumab
(Cinqair)
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Add-on maintenance therapy for severe asthma with an eosinophilic phenotype (18 years and older)
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IL-5 antagonist
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• 3 mg/kg once every 4 weeks administered as an I.V. infusion over 20 to 50 minutes.
• Must be administered in a health care setting.
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Benralizumab (Fasenra)
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Add-on maintenance therapy for severe asthma with an eosinophilic phenotype (12 years and older)
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IL-5 cytolytic monoclonal antibody
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• 30 mg administered as an S.C. injection once every 4 weeks for the first 3 doses, then once every 8 weeks.
• Should be administered under the guidance of a health care provider.
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Dupilumab
(Dupixent)
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Add-on maintenance therapy for moderate-to-severe asthma with an eosinophilic phenotype or with oral corticosteroid dependent asthma
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IL-4 receptor alpha antagonist
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• Initial loading dose of 400 mg or 600 mg administered as two S.C. injections followed by 200 mg or 300 mg. administered as an S.C. injection once every two weeks.
• Should be administered under the guidance of a health care provider.
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