# AstraZeneca’s Tezepelumab granted FDA Priority Review for asthma

- Link: https://www.directorstalkinterviews.com/astrazenecas-tezepelumab-granted-fda-priority-review-for-asthma/4121008620
- Published: 2021-07-08T07:21:58+01:00
- Author: Amilia Stone

**[AstraZeneca plc](https://www.directorstalkinterviews.com/ftse-company/astrazeneca/azn.l)**(
[LON:AZN](https://www.directorstalkinterviews.com/ftse-company/astrazeneca/azn.l))
Biologics License Application (BLA) for tezepelumab has been accepted and granted
Priority Review for the treatment of asthma from the US Food and Drug Administration(
FDA). Tezepelumab is being developed by AstraZeneca in collaboration with Amgen.

The FDA grants Priority Review to applications for medicines that offer significant
advantages over available options by demonstrating safety or efficacy improvements,
preventing serious conditions, or enhancing patient compliance.^(1) The Prescription
Drug User Fee Act date, the FDA action date for their regulatory decision, is during
the first quarter of 2022.

Despite recent advances in severe asthma, many patients may not qualify for or respond
well to current biologic medicines.^(2-5) Patients with severe, uncontrolled asthma
experience frequent exacerbations, significant limitations on lung function and 
a reduced quality of life.^(2,6,7)

The BLA was based on results from the PATHFINDER clinical trials programme, including
results from the pivotal NAVIGATOR Phase III trial. In NAVIGATOR, tezepelumab demonstrated
superiority across every primary and key secondary endpoint, compared to placebo,
in a broad population of patients with uncontrolled asthma while receiving treatment
with medium- or high-dose inhaled corticosteroids (ICS) plus at least one additional
controller medicine with or without oral corticosteroids (OCS).^(8)

There were no clinically meaningful differences in safety results between the tezepelumab
and placebo groups in the NAVIGATOR trial.^(8) The most frequently reported adverse
events with tezepelumab were nasopharyngitis, upper respiratory tract infection 
and headache.^(8)

Results from the NAVIGATOR Phase III trial were published in The New England Journal
of Medicine_ _in May 2021.

Tezepelumab received Breakthrough Therapy Designation for patients with severe asthma,
without an eosinophilic phenotype in September 2018.

**Severe asthma**

Asthma is a heterogeneous disease affecting an estimated 339 million people worldwide.
^(6,9) Approximately 10% of asthma patients have severe asthma.^(2,6) Despite the
use of inhaled asthma controller medicine, currently available biologic therapies
and oral corticosteroids (OCS), many severe asthma patients remain uncontrolled.
^(2,3,6) Due to the complexity of severe asthma, many patients have unclear or multiple
drivers of inflammation and may not qualify for or respond well to a current biologic
medicine.^(2-5)

Severe, uncontrolled asthma is debilitating with patients experiencing frequent 
exacerbations, significant limitations on lung function and a reduced quality of
life.^(2,6,7) Patients with severe asthma are at an increased risk of mortality 
and compared to patients with persistent asthma have twice the risk of asthma-related
hospitalisations.^(10-12) There is also a significant socio-economic burden, with
these patients accounting for 50% of asthma-related costs.^(13)

**Clinical trials**

Building on the Phase IIb PATHWAY trial, the Phase III PATHFINDER programme included
two trials, NAVIGATOR^(8,14) and SOURCE.^(15,16) The programme includes additional
planned mechanistic and long-term safety trials.^(17-19)

NAVIGATOR is a Phase III, randomised, 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 ICS plus at least one additional controller medicine with or without
OCS. The trial population included approximately equal proportions of patients with
high (≥ 300 cells/µL) and low (< 300 cells/µL) 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 medicines without change throughout the trial.^(8)

The primary efficacy endpoint was the annualised asthma exacerbation rate (AAER)
during the 52-week treatment period. Key secondary endpoints included the effect
of tezepelumab on lung function, asthma control and health-related quality of life.
^(8)

As part of prespecified analyses, the AAER over 52 weeks was also assessed in patients
grouped by baseline blood eosinophil count, fractional exhaled nitric oxide (FeNO)
level, serum specific immunoglobin E (IgE) status (perennial allergen sensitivity
positive or negative).^(8) These are inflammatory biomarkers used by clinicians 
to inform treatment options and involve tests analysing a patient’s blood (eosinophils/
IgE) and exhaled air (FeNO).

There were no clinically meaningful differences in safety results between the tezepelumab
and placebo groups in the NAVIGATOR trial.^(8) The most frequently reported adverse
events for tezepelumab were nasopharyngitis, upper respiratory tract infection and
headache.^(8)

NAVIGATOR is the first Phase III trial to show benefit in severe asthma irrespective
of eosinophils by targeting thymic stromal lymphopoietin (TSLP).^(8) These results
support the US Food and Drug Administration Breakthrough Therapy Designation granted
to tezepelumab in September 2018 for patients with severe asthma, without an eosinophilic
phenotype.

SOURCE is a Phase III multicentre, randomised, 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, and chronic treatment with maintenance
OCS therapy. The primary endpoint is the categorised percentage reduction from baseline
in the daily OCS dose, while not losing asthma control.^(16)

Patients who participated in the NAVIGATOR and SOURCE trials were eligible to continue
in DESTINATION, a Phase III extension trial assessing long-term safety and efficacy.
^(17)

**Tezepelumab**

Tezepelumab is a potential first-in-class human monoclonal antibody that inhibits
the action of TSLP, a key epithelial cytokine that sits at the top of multiple inflammatory
cascades and is critical in the initiation and persistence of allergic, eosinophilic
and other types of airway inflammation associated with severe asthma.^(20,21) TSLP
is released in response to multiple triggers associated with asthma exacerbations,
including allergens, viruses and other airborne particles.^(20,21) Expression of
TSLP is increased in the airways of patients with asthma and has been correlated
with disease severity.^(20,22) Blocking TSLP may prevent the release of pro-inflammatory
cytokines by immune cells, resulting in the prevention of asthma exacerbations and
improved asthma control.^(20,22) Tezepelumab acts at the top of the inflammation
cascade and has the potential to help address a broad population of severe asthma
patients regardless of their type of inflammation.^(20,22)

> **Mene Pangalos, Executive Vice President, AstraZeneca BioPharmaceuticals R&D,
> said**: “This decision brings us a step closer to delivering a much-needed, first-
> in-class medicine for asthma patients, many of whom remain uncontrolled and at
> risk of asthma attacks despite the availability of inhaled and biologic medicines.
> Tezepelumab has demonstrated reductions in exacerbations irrespective of blood
> eosinophil counts, allergy status and fractional exhaled nitric oxide, and has
> the potential to transform treatment for a broad population of severe asthma patients.”

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