Amgen today announced results from a pooled posthoc analysis of the pivotal NAVIGATOR Phase 3 and PATHWAY Phase 2b trials showed TEZSPIRE™ (tezepelumab-ekko) demonstrated reductions in the annualized asthma exacerbation rate (AAER) across biomarker subgroups of patients with severe asthma. These findings support the role of TEZSPIRE as a first-in-class treatment for a broad population of people living with severe asthma, irrespective of biomarker levels.
In the pooled analysis, TEZSPIRE, when added to standard of care (SoC), reduced asthma exacerbations in patients, irrespective of baseline blood eosinophil counts, demonstrating consistent efficacy with a 71% (≥300 cells per microliter), 48% (<300 cells per microliter) and 48% (<150 cells per microliter) reduction in the AAER over 52 weeks, compared to placebo added to SoC. In the same analysis, TEZSPIRE also demonstrated improvements in AAER in patients regardless of fractional exhaled nitric oxide (FeNO) level and allergy status over 52 weeks, compared to placebo.
Additionally, in a pre-specified exploratory analysis from NAVIGATOR, TEZSPIRE demonstrated consistent efficacy throughout the year regardless of the season. Data show that TEZSPIRE reduced the AAER by 63% (winter), 46% (spring), 62% (summer) and 54% (autumn) compared to placebo. The proportion of patients with an exacerbation was lower in the TEZSPIRE group than in the placebo group across all seasons.
“The majority of severe asthma patients have multiple drivers of inflammation, triggered by allergens, viral and bacterial infections, and air pollution, all of which can contribute to ongoing exacerbations. These new results highlight TEZSPIRE’s potential to reduce severe asthma exacerbations in patients irrespective of biomarker levels and seasonal triggers,” said Dr. Jonathan Corren, a clinical faculty member at the David Geffen School of Medicine, UCLA, and principal investigator of the PATHWAY trial.
“We’re thrilled to continue seeing patients experience fewer asthma attacks following treatment with TEZSPIRE based on results from the latest analyses in the NAVIGATOR and PATHWAY trials,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “These results further strengthen our belief that TEZSPIRE has the potential to be a transformative medicine for people living with severe asthma regardless of the season or their specific type of severe asthma.”
These results are being presented at the 2022 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.
TEZSPIRE is approved in the United States for the treatment of severe asthma and is under regulatory review in the EU, Japan, and several other countries around the world.
TEZSPIRE™ (tezepelumab-ekko) U.S. Indication
TEZSPIRE is indicated for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.
TEZSPIRE is not indicated for the relief of acute bronchospasm or status asthmaticus.
TEZSPIRE™ (tezepelumab-ekko) Important Safety Information
CONTRAINDICATIONS
Known hypersensitivity to tezepelumab-ekko or excipients.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions (e.g., rash and allergic conjunctivitis) can occur following administration of TEZSPIRE. These reactions can occur within hours of administration, but in some instances have a delayed onset (i.e., days). In the event of a hypersensitivity reaction, initiate appropriate treatment as clinically indicated and then consider the benefits and risks for the individual patient to determine whether to continue or discontinue treatment with TEZSPIRE.
Acute Asthma Symptoms or Deteriorating Disease
TEZSPIRE should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus.
Abrupt Reduction of Corticosteroid Dosage
Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with TEZSPIRE. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.
Parasitic (Helminth) Infection
It is unknown if TEZSPIRE will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with TEZSPIRE. If patients become infected while receiving TEZSPIRE and do not respond to anti-helminth treatment, discontinue TEZSPIRE until the infection resolves.
Live Attenuated Vaccines
The concomitant use of TEZSPIRE and live attenuated vaccines have not been evaluated. The use of live attenuated vaccines should be avoided in patients receiving TEZSPIRE.
ADVERSE REACTIONS
The most common adverse reactions (incidence ≥3%) are pharyngitis, arthralgia, and back pain.
USE IN SPECIFIC POPULATIONS
There are no available data on TEZSPIRE use in pregnant women to evaluate for any drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Placental transfer of monoclonal antibodies such as Tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy.
Please see the TEZSPIRE full Prescribing Information.
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About the NAVIGATOR and the PATHFINDER Clinical Trial Program
The PATHFINDER clinical trial program for TEZSPIRE included the Phase 2b PATHWAY and Phase 3 NAVIGATOR trials. The program also includes an oral corticosteroid-sparing trial, a mechanistic trial, and a long-term safety trial.
PATHWAY is a Phase 2b, randomized, double-blind, parallel-group, placebo-controlled, 52-week trial designed to evaluate the efficacy and safety of three-dose regimens of TEZSPIRE, 70mg and 210mg every four weeks and 280mg every two weeks, as add-on therapy in patients with a history of asthma exacerbations and uncontrolled asthma receiving inhaled corticosteroids/long-acting beta-agonist with or without oral corticosteroids and additional asthma controllers.
NAVIGATOR is a Phase 3, randomized, double-blinded, placebo-controlled trial in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma, who were receiving standard of care (SoC). SoC was treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without daily OCS treatment. The trial population included approximately equal proportions of patients with high (≥300 cells per microliter) and low (<300 cells per microliter) blood eosinophil counts. The trial comprised a five-to-six-week screening period, a 52-week treatment period, and a 12-week post-treatment follow-up period. All patients received their prescribed controller medications without change throughout the trial.
The primary efficacy endpoint was the annualized asthma exacerbation rate (AAER) during the 52-week treatment period. Key secondary endpoints included the effect of TEZSPIRE on lung function, asthma control, and health-related quality of life.
As part of prespecified analyses, the AAER over 52 weeks was also assessed in patients grouped by baseline blood eosinophil count, FeNO level, and serum specific immunoglobin E (IgE) status (perennial aeroallergen sensitivity positive or negative). These are inflammatory biomarkers used by clinicians to inform treatment options and involve tests analyzing a patient’s blood (eosinophils/IgE) and exhaled air (FeNO).
The NAVIGATOR results showed a statistically significant and clinically meaningful reduction in the primary endpoint of AAER over 52 weeks in the overall patient population.4 Clinically meaningful reductions in AAER compared to placebo were observed in the TEZSPIRE-treated patients irrespective of blood eosinophil counts, FeNO level, and allergy status. There were no clinically meaningful differences in safety results between the TEZSPIRE and placebo groups in the NAVIGATOR trial. The most frequently reported adverse events for TEZSPIRE were nasopharyngitis, upper respiratory tract infection, and headache.
The findings from the pooled analysis build on the PATHWAY and NAVIGATOR results previously published in The New England Journal of Medicine.
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NAVIGATOR and PATHWAY pooled post-hoc analysis: |
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Subgroup |
AAER results over 52 weeks TEZSPIRE added to SoC versus placebo added to SoC |
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Baseline blood eosinophil counts (≥300 cells per microliter) |
71% reduction (95% CI: 62, 78) |
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Baseline blood eosinophil counts (≥150 to <300 cells per microliter) |
48% reduction (95% CI: 28, 62) |
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Baseline blood eosinophil counts (<150 cells per microliter) |
48% reduction (95% CI: 26, 64) |
|
FeNO levels (<25 parts per billion) |
40% reduction (95% CI: 21, 54) |
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FeNO levels (≥25 parts per billion) |
70% reduction (95% CI: 62, 76) |
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Positive allergy to perennial aeroallergens |
62% reduction (95% CI: 53, 70) |
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Negative allergy to perennial aeroallergens |
54% reduction (95% CI: 38, 66)
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CI: Confidence interval
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NAVIGATOR pre-specified seasonality analysis: |
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Subgroup |
AAER results over 52 weeks |
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Winter |
63% reduction (95% CI: 52, 72) |
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Spring |
46% reduction (95% CI: 26, 61) |
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Summer |
62% reduction (95% CI: 48, 73) |
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Autumn |
54% reduction (95% CI: 41, 64) |
CI: Confidence interval
NAVIGATOR is the first Phase 3 trial to show benefit in severe asthma irrespective of eosinophils by targeting the cytokine thymic stromal lymphopoietin (TSLP). These results support the FDA Breakthrough Therapy Designation granted to TEZSPIRE in September 2018 for patients with severe asthma, without an eosinophilic phenotype. In July 2021, TEZSPIRE was the first and only biologic to be granted Priority Review in the U.S. for the treatment of asthma by the FDA. Patients who participated in our Phase 3 trials were eligible to continue in DESTINATION, a Phase 3 extension trial assessing long-term safety and efficacy.
