# AstraZeneca’s Tezspire recommended for marketing authorisation in the EU

- Link: https://www.directorstalkinterviews.com/astrazenecas-tezspire-recommended-for-marketing-authorisation-in-the-eu/4121074332
- Published: 2022-07-25T07:44:13+01:00
- Author: Amilia Stone

**AstraZenec plc **([LON:AZN](https://www.directorstalkinterviews.com/ftse-company/astrazeneca/azn.l))
_Tezspire_ (tezepelumab) has been recommended for marketing authorisation in the
European Union (EU) as an add-on therapy in patients 12 years and older with severe
asthma who are inadequately controlled with high dose inhaled corticosteroids plus
another medicinal product for maintenance treatment.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines
Agency based its positive opinion on results from the PATHFINDER clinical trial 
programme. The marketing authorisation 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.^(1)

_Tezspire_ is the first and only biologic for severe asthma that acts at the top
of the inflammatory cascade by blocking thymic stromal lymphopoietin (TSLP), an 
epithelial cytokine.^(1-4) _Tezspire_ consistently and significantly reduced 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).^(1,2)

> **Dr. Stephanie Korn, Senior Physician in Pneumology and Respiratory Medicine 
> at IKF Pneumologie Mainz and Thoraxklinik Heidelberg, Germany, and investigator
> for the NAVIGATOR trial said**: “Due to the complexity of severe asthma, about
> 60% of patients have multiple drivers of inflammation. _Tezspire_ is a first-in-
> class biologic acting at the top of the inflammation cascade and a much-needed
> potential treatment for patients who continue to struggle with severe, uncontrolled
> asthma.”

> **Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca,
> said**: “Despite recent advances in treatment, many asthma patients continue to
> experience debilitating symptoms, an increased risk of hospitalisation, and even
> death. The only biologic recommended for EU approval in severe asthma patients
> with no phenotype or biomarker limitation, _Tezspire_ has consistently and significantly
> reduced exacerbations in clinical trials, and has the potential to transform care
> for a broad population of severe asthma patients.”

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.^(1)

In clinical trials, the most common adverse events in patients who received _Tezspire_
were pharyngitis, rash, arthralgia and injection site reactions.^(5)

_Tezspire_ was approved as an add-on maintenance treatment of adult and paediatric
patients aged 12 years and older with severe asthma in the US in December 2021 and
is under regulatory review in Japan and many other countries around the world.^(
6)

**Notes**

**Severe asthma**

Asthma is a heterogeneous disease affecting approximately 14 million people living
with the disease in the European Union and an estimated 339 million people worldwide.
^(7,8) Up to 10% of asthma patients have severe asthma.^(9,10) Despite the use of
inhaled asthma controller medicine, currently available biologic therapies and oral
corticosteroids (OCS), many severe asthma patients remain uncontrolled.^(9-11) 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.
^(10-13)

Severe, uncontrolled asthma is debilitating with patients experiencing frequent 
exacerbations, significant limitations on lung function and a reduced quality of
life.^(9,10,14) 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.^(15-17) There is also a significant socio-economic burden, with
these patients accounting for approximately 50% of asthma-related costs.^(18)

**Clinical trials**

In addition to the Phase IIb PATHWAY trial, the PATHFINDER programme included two
Phase III trials, NAVIGATOR^(1,19) and SOURCE.^(20,21) The programme also includes
additional mechanistic and long-term safety trials.^(22,23)

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.^(1)

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.
^(1)

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).^(1) 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.^(1) The most frequently reported adverse
events for _Tezspire_ were nasopharyngitis, upper respiratory tract infection and
headache.^(1)

NAVIGATOR is the first Phase III trial to show benefit in severe asthma irrespective
of eosinophils by targeting TSLP.^(1) 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.^(22)

**_Tezspire_**

_Tezspire_ (tezepelumab) is being developed by AstraZeneca in collaboration with
Amgen as a 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.^(2,3) TSLP is released in response to multiple triggers associated
with asthma exacerbations, including allergens, viruses and other airborne particles.
^(2,3) Expression of TSLP is increased in the airways of patients with asthma and
has been correlated with disease severity.^(2,4) Blocking TSLP may prevent the release
of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma
exacerbations and improved asthma control.^(1,2,4) _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.^(1,2)

_Tezspire_ is approved in the US for the add-on maintenance treatment of adult and
paediatric patients aged 12 years and older with severe asthma.^(6) _Tezspire_ is
also in development for other potential indications including chronic obstructive
pulmonary disease (COPD), 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.

Share on: