New Tezepelumab Data Show 86% Reduction In Exacerbations In Patients With Severe Asthma And Comorbid Nasal Polyps
09.05.2021
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The pre-specified exploratory analysis evaluated the effect of tezepelumab in NAVIGATOR patients with or without reported nasal polyps (NP+ or NP−) in the past two years. The analysis showed tezepelumab achieved an 86% reduction in the annualized asthma exacerbation rate (AAER) in NP+ patients (95% CI: 70, 93) and 52% (95% CI: 42, 61) in NP− patients over 52 weeks, compared to placebo when added to standard of care (SoC).1
Tezepelumab improved lung function at week 52 in both groups of patients with an increase in pre-bronchodilator forced expiratory volume in one second (FEV1) of 0.20 L (95% CI: 0.02, 0.37) and 0.13 L (95% CI: 0.08, 0.18) versus placebo in NP+ and NP− patients, respectively.1 Tezepelumab also achieved a clinically relevant improvement in nasal polyp symptoms at week 52, as measured by the Sinonasal Outcome Test (SNOT-22), reducing the SNOT-22 score in NP+ patients by 9.6 points (95% CI: 0.9, 18.2) versus placebo.1,4 The adjusted mean score reductions from baseline for tezepelumab and placebo were 20.10 points (SE: 3.07) and 10.55 points (SE: 2.94). Baseline mean (sd) SNOT-22 score was 49.4 (21.5) and 47.8 (19.0) for tezepelumab and placebo, respectively.1
"This new analysis from NAVIGATOR is exciting for the up to one in five severe asthma patients who have comorbid nasal polyps," said Professor
"We're thrilled to see significant reductions in exacerbations experienced by patients with severe asthma and comorbid nasal polyps as noted within the latest analysis of NAVIGATOR data," said
These findings were presented at the
Results from the NAVIGATOR Phase 3 trial were published in the
About Severe Asthma
Globally, there are approximately 2.5 million patients with severe asthma who are uncontrolled or biologic eligible, with approximately 1 million in the U.S. Many patients with severe asthma have an inadequate response to currently available biologics and oral corticosteroids and thus fail to achieve asthma control.7,8,9 Uncontrolled asthma occurs when symptoms persist despite treatment. Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life. 7,8,9 Patients with severe uncontrolled asthma have twice the risk of asthma-related hospitalizations.10,11 There is also a significant socio-economic burden with these severe uncontrolled asthma patients accounting for 50% of asthma-related costs.12
Multiple inflammatory pathways are involved in the pathogenesis of asthma.13-15 Eosinophilic asthma, and more broadly, T2 inflammation-driven asthma, accounts for about two-thirds of patients with severe asthma.15 These patients are typically characterized as having elevated levels of inflammatory biomarkers, including blood eosinophils, serum IgE and fractional exhaled nitric oxide (FeNO).16,17 However, many patients do not fit the criteria for eosinophilic or allergic asthma, may have unclear or multiple drivers of inflammation, and may not qualify for or respond well to a current biologic medicine.17
Nasal polyps are benign growths that arise from the mucosa of the nose and paranasal sinuses.18 Up to 22% of severe asthma patients have comorbid nasal polyps.19 Nasal polyps can block nasal passages and lead to breathing problems, reduction in the sense of smell, nasal discharge, sleep disturbance and other adverse effects on quality of life.20-22
About the NAVIGATOR and the PATHFINDER Clinical Trial Program
Building on the Phase 2b PATHWAY trial, the Phase 3 PATHFINDER program included two trials, NAVIGATOR5,23 and SOURCE.24,25 The program includes additional planned mechanistic and long-term safety trials.26 In addition, a Phase 3 clinical trial, WAYPOINT, has been initiated to explore the efficacy and safety of tezepelumab in adults with severe, chronic rhinosinusitis with nasal polyps.6
NAVIGATOR is a Phase 3, randomized, double-blinded, placebo-controlled trial in 1,061 adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma, who were receiving treatment with medium- or high-dose inhaled corticosteroids (ICS) plus at least one additional controller medication with or without OCS. Of the 1,061 randomized patients, 1,059 received either tezepelumab 210 mg (n=528) or placebo (n=531). In total for this pre-specified exploratory analysis, 83 patients had NP in the past 2 years (tezepelumab 210 mg, n=42; placebo, n=41) and 976 did not (tezepelumab 210 mg, n=486; placebo, n=490). NAVIGATOR met the primary endpoint with tezepelumab added to SoC demonstrating a statistically significant and clinically meaningful reduction in the AAER over 52 weeks in the overall patient population, compared to placebo added to SoC. The trial also met the primary endpoint in the subgroup of patients with baseline eosinophil counts less than 300 cells per microliter, with tezepelumab demonstrating a statistically significant and clinically meaningful reduction in AAER in that patient population. Similar reductions in AAER were observed in the subgroup of patients with baseline eosinophil counts less than 150 cells per microliter.26,27
NAVIGATOR primary endpoints5 |
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Endpoint |
Timepoint |
Annual Exacerbation Rate |
Results Tezepelumab added to SoC vs placebo added to SoC |
|
Tezepelumab |
Placebo |
|||
AAER – overall patient population |
Over 52 weeks |
0.93 (95% CI: 0.80, 1.07) |
2.10 (95% CI: 1.84, 2.39) |
56% reduction (95% CI: 47, 63; p<0.001) |
AAER – baseline eosinophil counts < 300 cells/µL |
Over 52 weeks |
1.02 (95% CI: 0.84, 1.23) |
1.73 (95% CI: 1.46, 2.05) |
41% reduction (95% CI: 25, 54; p<0.001) |
CI: Confidence interval |
NAVIGATOR pre-specified exploratory analysis: AAER in patients with severe, uncontrolled asthma with or without nasal polyps in the two years before randomization1 |
|
Subgroup |
AAER results over 52 weeks Tezepelumab added to SoC versus placebo added to SoC (relative risk reduction and annualized exacerbation rates) |
Severe uncontrolled asthma with reported nasal polyps (NP+) |
86% reduction (95% CI: 70, 93) |
Severe uncontrolled asthma without reported nasal polyps (NP-) |
52% reduction (95% CI: 42, 61) · Placebo: 2.05 (95% CI: 1.79, 2.35) |
CI: Confidence interval |
NAVIGATOR pre-specified exploratory analysis: Pre-bronchodilator FEV1 in patients with severe, uncontrolled asthma with or without nasal polyps in the two years before randomization1 |
|
Subgroup |
Pre-bronchodilator FEV1 over 52 weeks Tezepelumab added to SoC versus placebo added to SoC (LS mean difference and LS mean change from baseline) |
Severe uncontrolled asthma with reported nasal polyps (NP+) |
0.20 L (95% CI: 0.02, 0.37) · Tezepelumab: 0.32 (SE: 0.064) · Placebo: 0.13 (SE: 0.064) |
Severe uncontrolled asthma without reported nasal polyps (NP-) |
0.13 L (95% CI: 0.08, 0.18) · Tezepelumab: 0.22 (SE: 0.019) · Placebo: 0.09 (SE: 0.019) |
LS: Least-squares, CI: Confidence interval, SE: Standard error |
NAVIGATOR is the first Phase 3 trial to show benefit in severe asthma irrespective of eosinophils by targeting the thymic stromal lymphopoietin (TSLP). The U.S. Food and Drug Administration Breakthrough Therapy Designation was granted to tezepelumab in September 2018 for patients with severe asthma, without an eosinophilic phenotype.
SOURCE is a Phase 3 multicenter, randomized, double-blinded, parallel-group, placebo-controlled trial for 48 weeks in adult patients with severe asthma who require continuous treatment with ICS plus long-acting beta2-agonists (LABA), and chronic treatment with maintenance OCS therapy. In the trial, patients were randomized to receive tezepelumab 210 mg every four weeks or placebo as add-on therapy, with patients maintained on their currently prescribed ICS plus LABA, with or without other asthma controller therapy.
Patients who participated in the NAVIGATOR and SOURCE trials were eligible to continue in DESTINATION, a Phase 3 extension trial assessing long-term safety and efficacy.28
About Tezepelumab
Tezepelumab is being developed by AstraZeneca in collaboration with
TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles.2,29 Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity.2,3 Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control.2,3 By working at the top of the cascade, tezepelumab helps stop inflammation at the source and has the potential to treat a broad population of severe asthma patients.2,3
About the
In 2020,
For more than two decades,
Our commitment to patients is reflected not only in where we have succeeded, but in where we have failed and opened new doors. Throughout, we have remained dedicated to the principle of leading with science, pursuing where pathways and promising discoveries in inflammation take us, and not relenting until innovative solutions for patients are found. It's a commitment that extends beyond introducing novel therapies. We are focused on improving the entire patient journey.
About
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This news release contains forward-looking statements that are based on the current expectations and beliefs of
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References
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