# AstraZeneca & Amgen’s Tezspire approved in the US for severe asthma

- Link: https://www.directorstalkinterviews.com/astrazeneca-amgens-tezspire-approved-in-the-us-for-severe-asthma/4121039640
- Published: 2021-12-20T07:19:06+00:00
- 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))
and Amgen’s _Tezspire_ (tezepelumab-ekko) has been approved in the US for the add-
on maintenance treatment of adult and paediatric patients aged 12 years and older
with severe asthma.^(1)

_Tezspire_ was approved following a Priority Review by the US Food and Drug Administration(
FDA) and based on results from the PATHFINDER clinical trial programme. The application
included results from the pivotal NAVIGATOR Phase III trial in which _Tezspire_ 
demonstrated superiority across every primary and key secondary endpoint in patients
with severe asthma, compared to placebo, when added to standard therapy.^(2)

_Tezspire_ is a first-in-class biologic for severe asthma that acts at the top of
the inflammatory cascade by targeting thymic stromal lymphopoietin (TSLP), an epithelial
cytokine.^(2-5) It is the first and only biologic to consistently and significantly
reduce asthma exacerbations across Phase II and III clinical trials which included
a broad population of severe asthma patients irrespective of key biomarkers, including
blood eosinophil counts, allergic status and fractional exhaled nitric oxide (FeNO).
^(2,3,6-13) _Tezspire_ is the only biologic approved for severe asthma with no phenotype(
e.g. eosinophilic or allergic) or biomarker limitation within its approved label.
^(1) 

> **Professor Andrew Menzies-Gow, Director of the Lung Division, Royal Brompton 
> Hospital, London, UK, and principal investigator of the NAVIGATOR trial, said**:“
> Due to the complex and heterogeneous nature of severe asthma and despite recent
> advances, many patients continue to experience frequent exacerbations, an increased
> risk of hospitalisation and a significantly reduced quality of life. _Tezspire_
> represents a much-needed new treatment for the many patients who remain underserved
> and continue to struggle with severe, uncontrolled asthma.”

> **Tonya Winders, President and CEO of Allergy & Asthma Network, and President 
> of the Global Allergy and Airways Patient Platform, said**: “Severe asthma continues
> to have a debilitating impact on many of the 34 million people living with the
> disease worldwide, affecting their breathing and limiting aspects of day-to-day
> life. The approval of _Tezspire_ is long-awaited positive news for the asthma 
> community. For the first time, many people living with severe asthma have the 
> opportunity to receive treatment regardless of the cause of their inflammation.”

> **Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca,
> said**: “Today’s positive decision marks the first time the FDA has approved a
> biologic for asthma without phenotypic limitation and irrespective of biomarker
> levels. With the approval of _Tezspire,_ physicians will now be able to offer 
> an important new treatment that has the potential to transform care for a broad
> population of severe asthma patients.”

In clinical studies, the most common adverse reactions in patients who received 
_Tezspire_ were pharyngitis, arthralgia and back pain.^(1)

Results from the NAVIGATOR Phase III trial were published in The New England Journal
of Medicine in May 2021. There were no clinically meaningful differences in safety
results between the _Tezspire_ and placebo groups in the NAVIGATOR trial.^(2)

The application for _Tezspire_ was granted Priority Review, a designation given 
to applications for medicines that offer significant advantages over available options
by demonstrating safety or efficacy improvements, preventing serious conditions,
or enhancing patient compliance.^(14)

_Tezspire_ is under regulatory review in the EU, Japan and several other countries
around the world.

**Notes**

**Severe asthma**

Asthma is a heterogeneous disease affecting an estimated 339 million people worldwide.
^(15,16) Approximately 10% of asthma patients have severe asthma.^(16,17) Despite
the use of inhaled asthma controller medicine, currently available biologic therapies
and oral corticosteroids (OCS), many severe asthma patients remain uncontrolled.
^(16-18) 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.^(17-20)

Severe, uncontrolled asthma is debilitating with patients experiencing frequent 
exacerbations, significant limitations on lung function and a reduced quality of
life.^(16,17,21) 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.^(22-24) There is also a significant socio-economic burden, with
these patients accounting for approximately 50% of asthma-related costs.^(25)

**Clinical trials**

In addition to the Phase IIb PATHWAY trial, the PATHFINDER programme included two
Phase III trials, NAVIGATOR^(2,26) and SOURCE.^(27,28) The programme also includes
additional mechanistic and long-term safety trials.^(29,30)

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 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 microlitre) and low (<300
cells per microlitre) 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.^(2)

The primary efficacy endpoint was the annualised 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.
^(2)

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).^(2) 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 _Tezspire_
and placebo groups in the NAVIGATOR trial.^(2) The most frequently reported adverse
events for _Tezspire_ were nasopharyngitis, upper respiratory tract infection and
headache.^(2)

NAVIGATOR is the first Phase III trial to show benefit in severe asthma irrespective
of eosinophils by targeting TSLP.^(2) 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 US for the treatment of asthma
by the FDA.

Patients who participated in our Phase III trials were eligible to continue in DESTINATION,
a Phase III extension trial assessing long-term safety and efficacy.^(29)

**Tezspire**

_Tezspire_ (tezepelumab) is being developed by AstraZeneca in collaboration with
Amgen as 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, including 
airway hyperresponsiveness.^(3,4) TSLP is released in response to multiple triggers
associated with asthma exacerbations, including allergens, viruses and other airborne
particles.^(3,4) Expression of TSLP is increased in the airways of patients with
asthma and has been correlated with disease severity.^(3,5) Blocking TSLP may prevent
the release of pro-inflammatory cytokines by immune cells, resulting in the prevention
of asthma exacerbations and improved asthma control.^(2,3,5) _Tezspire_ acts at 
the top of the inflammation cascade and has the potential to help address a broad
population of severe asthma patients irrespective of biomarker levels.^(2,3)

_Tezspire_ is also in development for other potential indications including chronic
obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, chronic
spontaneous urticaria and eosinophilic esophagitis (EoE). In October 2021, tezepelumab
was granted Orphan Drug Designation by the FDA for the treatment of EoE.

**Amgen collaboration**

In 2020, Amgen and AstraZeneca updated a 2012 collaboration agreement for _Tezspire_.
Both companies will continue to share costs and profits equally after payment by
AstraZeneca of a mid single-digit inventor royalty to Amgen. AstraZeneca continues
to lead development and Amgen continues to lead manufacturing. All aspects of the
collaboration are under the oversight of joint governing bodies. Under the amended
agreement, Amgen and AstraZeneca will jointly commercialize _Tezspire_ in North 
America. Amgen will record product sales in the US, with AZ recording its share 
of US profits as Collaboration Revenue. Outside of the US, AstraZeneca will record
product sales, with Amgen recording profit share as Other/Collaboration revenue.

**AstraZeneca in Respiratory & Immunology**

Respiratory & Immunology, part of BioPharmaceuticals, is one of AstraZeneca’s main
disease areas and is a key growth driver for the Company.

AstraZeneca is an established leader in respiratory care with a 50-year heritage.
The Company aims to transform the treatment of asthma and chronic obstructive pulmonary
disease (COPD) by focusing on earlier biology-led treatment, eliminating preventable
asthma attacks, and removing COPD as a top-three leading cause of death. The Company’s
early respiratory research is focused on emerging science involving immune mechanisms,
lung damage and abnormal cell-repair processes in disease and neuronal dysfunction.

With common pathways and underlying disease drivers across respiratory and immunology,
AstraZeneca is following the science from chronic lung diseases to immunology-driven
disease areas. The Company’s growing presence in immunology is focused on five mid-
to late-stage franchises with multi-disease potential, in areas including rheumatology(
including systemic lupus erythematosus), dermatology, gastroenterology, and systemic
eosinophilic-driven diseases. AstraZeneca’s ambition in Respiratory & Immunology
is to achieve disease modification and durable remission for millions of patients
worldwide.

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