REG - AstraZeneca PLC - Update on US review of Fasenra in nasal polyps

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14/03/2022 07:00

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RNS Number : 5901E  AstraZeneca PLC  14 March 2022

14 March 2022 07:00 GMT

 

Update on US regulatory review of Fasenra

in chronic rhinosinusitis with nasal polyps

 

The US Food and Drug Administration (FDA) has issued a complete response
letter (CRL) regarding the supplemental Biologics License Application (sBLA)
for Fasenra (benralizumab) for patients with inadequately controlled chronic
rhinosinusitis with nasal polyps (CRSwNP).

 

The sBLA submitted to the FDA by AstraZeneca included data from the OSTRO
Phase III trial, which met both co-primary endpoints with a safety profile
consistent with the known profile of the medicine.(1) The CRL requested
additional clinical data and the Company is working closely with the FDA
regarding next steps. The Company remains committed to bringing Fasenra to
patients with CRSwNP and a second Phase III trial, ORCHID
(https://clinicaltrials.gov/ct2/show/NCT04157335) , in this indication is
ongoing.(2)

 

Fasenra is currently approved as an add-on maintenance treatment for severe
eosinophilic asthma in the US, EU, Japan and other countries and is approved
for self-administration in the US, EU and other countries.

 

The FDA granted Orphan Drug Designation (ODD) for Fasenra for eosinophilic
granulomatosis with polyangiitis in 2018, and hypereosinophilic syndrome and
eosinophilic esophagitis (EoE) in 2019. In November 2021, the FDA also granted
ODD
(https://www.astrazeneca.com/content/astraz/media-centre/medical-releases/fasenra-granted-orphan-drug-and-fast-track-designations-in-the-us-for-eosinophilic-gastritis-and-eosinophilic-gastroenteritis.html)
for Fasenra for eosinophilic gastroenteritis (EGE) and eosinophilic
gastritis (EG), and a Fast Track Designation
(https://www.astrazeneca.com/content/astraz/media-centre/medical-releases/fasenra-granted-orphan-drug-and-fast-track-designations-in-the-us-for-eosinophilic-gastritis-and-eosinophilic-gastroenteritis.html)
for the treatment of EG with or without EGE in the US.

 

Notes

 

CRSwNP

CRSwNP is characterised by persistent inflammation of the mucous membrane
lining the nasal passages and sinuses accompanied by benign growths, called
nasal polyps.(3,4) 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.(5-7) Eosinophilic infiltration
of the tissues is thought to play a role in the disease pathophysiology.(4,5)

 

Current treatments for nasal polyps include intranasal corticosteroids (INCS)
or oral corticosteroids and surgery to remove polyps, but these often provide
only short-term relief and the need for repeated interventions can be
high.(8,9) Since 2019, other biologic medicines have been approved or
recommended to treat nasal polyps.(6,10-12)

 

OSTRO

OSTRO was a randomised, double-blinded, multi-centre, parallel-group, 56-week
Phase III trial to evaluate the efficacy and safety of Fasenra compared to
placebo in patients with nasal polyposis.(1) Fasenra was evaluated in
patients, regardless of blood eosinophil count with or without asthma, who
were symptomatic despite standard of care therapy, including current use of
INCS for at least four weeks prior to enrolment and a history of systemic
corticosteroid use and/or surgery for nasal polyps.(1) Patients were
randomised to receive either Fasenra 30mg or placebo subcutaneously every four
weeks for the first three doses and every eight weeks thereafter.(1)

 

The primary outcome measures of the trial were: the effect of Fasenra on nasal
polyp burden, assessed by change from baseline in endoscopic total nasal polyp
score, at week 40 compared to placebo; the effect of Fasenra on
patient-reported nasal blockage, assessed by change from baseline in mean
nasal blockage score (NBS), at week 40 compared to placebo.(1) OSTRO involved
413 patients in Europe and North America.(1)

 

OSTRO is part of AstraZeneca's clinical trial programme for Fasenra in CRSwNP
which also includes the ongoing Phase III ORCHID trial, among others.(2)

 

ORCHID

ORCHID is a randomised, double-blinded, multi-centre, parallel-group, 56-week
Phase III trial to evaluate the efficacy and safety of Fasenra compared to
placebo in patients with eosinophilic CRSwNP.(2) The primary outcome measures
of the trial are: the effect of Fasenra on nasal polyp burden, assessed by
change from baseline in endoscopic total nasal polyp score, at week 56
compared to placebo; the effect of Fasenra on patient-reported nasal blockage,
assessed by change from baseline in mean NBS, at week 56 compared to
placebo.(2) The trial is expected to read out in the second half of 2023.

 

Fasenra

Fasenra (benralizumab) is a monoclonal antibody that binds directly to IL-5
receptor alpha on eosinophils and attracts natural killer cells to induce
rapid and near-complete depletion of blood and tissue eosinophils in most
patients via apoptosis (programmed cell death).(13,14) Nasal polyps are a
strong indicator of the eosinophilic phenotype in severe asthma and response
to Fasenra, including reductions in exacerbation and improvement in lung
function.(15-17)

 

Fasenra is currently approved as an add-on maintenance treatment for severe
eosinophilic asthma in the US, EU, Japan and other countries, and is approved
for self-administration in the US, EU and other countries.

 

Fasenra is in development for other eosinophilic diseases including atopic
dermatitis, bullous pemphigoid, chronic obstructive pulmonary disease, chronic
spontaneous urticaria, EoE, EG/EGE, EGPA, HES and non-cystic fibrosis
bronchiectasis.(18-26)

 

Fasenra was developed by AstraZeneca and is in-licensed from BioWa, Inc., a
wholly owned subsidiary of Kyowa Kirin Co., Ltd., Japan.

 

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 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.

 

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical
company that focuses on the discovery, development, and commercialisation of
prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals,
including Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries
and its innovative medicines are used by millions of patients worldwide.
Please visit astrazeneca.com (http://www.astrazeneca.com)  and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca)

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1.   Bachert C, et al. Efficacy and safety of benralizumab in chronic
rhinosinusitis with nasal polyps: A randomized, placebo-controlled trial. J
Allergy Clin Immunol. 2021; [IN PRESS]. DOI:
https://doi.org/10.1016/j.jaci.2021.08.030
(https://doi.org/10.1016/j.jaci.2021.08.030) .

2.   Clinicaltrials.gov. Efficacy and Safety Study of Benralizumab in
Patient With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID).
Available at: https://clinicaltrials.gov/ct2/show/NCT04157335
(https://clinicaltrials.gov/ct2/show/NCT04157335) . [Last accessed: February
2022].

3.   Bachert C, et al. Phenotypes and Emerging Endotypes of Chronic
Rhinosinusitis. J Allergy Clin Immunol Pract. 2016; 4 (4): 621-628.

4.   Newton JR, et al. A review of nasal polyposis. Ther Clin Risk Manag.
2008; 4 (2): 507-512.

5.   Hopkins C. Chronic Rhinosinusitis with Nasal Polyps. N Engl J Med.
2019; 381 (1): 55-63.

6.   Stevens WW, et al. Chronic Rhinosinusitis with Nasal Polyps. J Allergy
Clin Immunol Pract. 2016; 4 (4): 565-572.

7.   Abdalla S, et al. Prevalence of sinonasal outcome test (SNOT-22)
symptoms in patients undergoing surgery for chronic rhinosinusitis in the
England and Wales National prospective audit. Clin Otolaryngol. 2012; 37 (4):
276-282.

8.   Ren L, et al. Biologics for the treatment of chronic rhinosinusitis
with nasal polyps - state of the art. World Allergy Organ J.
2019;12(8):100050.

9.   DeConde AS, et al. Prevalence of polyp recurrence after endoscopic
sinus surgery for chronic rhinosinusitis with nasal polyposis. The
Laryngoscope. 2017; 127 (3): 550-555.

10.  Xolair (omalizumab) US prescribing information; 2021.

11.  Dupixent (dupilumab) US prescribing information; 2021.

12.  Nucala (mepolizumab) US prescribing information; 2022.

13.  Kolbeck R, et al. MEDI-563, a humanized anti-IL-5 receptor α mAb with
enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy
Clin Immunol. 2010; 125: 1344-1353.

14.  Pham T, et al. Reductions in eosinophil biomarkers by benralizumab in
patients with asthma. Respir Med. 2016; 111: 21-29.

15.  Bleecker ER, et al. Efficacy and safety of benralizumab for patients
with severe asthma uncontrolled with high-dosage inhaled corticosteroids and
long-acting β2-agonists (SIROCCO): a randomised, multicentre,
placebo-controlled phase 3 trial. Lancet. 2016;388:2115-2127.

16.  FitzGerald JM, et al. Benralizumab, an anti-interleukin-5 receptor alpha
monoclonal antibody, as add-on treatment for patients with severe,
uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind,
placebo-controlled phase 3 trial. Lancet. 2016;388:2128-2141.

17.  Canonica S, et al. Benralizumab improves symptoms of patients with
severe, eosinophilic asthma with a diagnosis of nasal polyposis. Allergy.
2022;77:150-161.

18.  Clinicaltrials.gov. Efficacy and Safety Study of the Use of Benralizumab
for Patients With Moderate to Severe Atopic Dermatitis. Available at:
https://www.clinicaltrials.gov/ct2/show/NCT04605094
(https://www.clinicaltrials.gov/ct2/show/NCT04605094) . [Last accessed:
February 2022].

19.  ClinicalTrials.gov. A Study to Investigate the Use of Benralizumab in
Patients With Bullous Pemphigoid. (FJORD). Available at:
https://clinicaltrials.gov/ct2/show/NCT04612790
(https://clinicaltrials.gov/ct2/show/NCT04612790) . [Last accessed: February
2022].

20.  Clinicaltrials.gov. Efficacy and Safety of Benralizumab in Moderate to
Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of
Frequent Exacerbations (RESOLUTE). Available at:
https://clinicaltrials.gov/ct2/show/NCT04053634
(https://clinicaltrials.gov/ct2/show/NCT04053634) . [Last accessed: February
2022].

21.  Clinicaltrials.gov. A Study to Investigate the Use of Benralizumab in
Patients With Moderate to Severe Chronic Spontaneous Urticaria. (ARROYO).
Available at: https://www.clinicaltrials.gov/ct2/show/NCT04612725
(https://www.clinicaltrials.gov/ct2/show/NCT04612725) . [Last accessed:
February 2022].

22.  Clinicaltrials.gov. A Study of Benralizumab in Patients With
Eosinophilic Esophagitis (MESSINA). Available at:
https://clinicaltrials.gov/ct2/show/NCT04543409
(https://clinicaltrials.gov/ct2/show/NCT04543409) . [Last accessed: February
2022].

23.  AstraZeneca Data on File (HUDSON trial).

24.  Clinicaltrials.gov. A Study to Evaluate if Benralizumab Compared to
Mepolizumab May be Beneficial in the Treatment of Eosinophilic Granulomatosis
With Polyangiitis (EGPA) (MANDARA). Available at:
https://clinicaltrials.gov/ct2/show/NCT04157348
(https://clinicaltrials.gov/ct2/show/NCT04157348) . [Last accessed: February
2022].

25.  Clinicaltrials.gov. A Phase 3 Study to Evaluate the Efficacy and Safety
of Benralizumab in Patients With Hypereosinophilic Syndrome (HES) (NATRON).
Available at: https://clinicaltrials.gov/ct2/show/NCT04191304
(https://clinicaltrials.gov/ct2/show/NCT04191304) . [Last accessed: February
2022].

26.  EU Clinical Trials Register. A Multicentre, Randomised, Double-blind,
Parallel-group, Placebo-controlled, 52-Week, Phase III Study With an
Open-label Extension to Evaluate the Efficacy and Safety of Benralizumab in
Patients With Non-Cystic Fibrosis Bronchiectasis (MAHALE). EudraCT number:
2020-004068-24. Available at:
https://www.clinicaltrialsregister.eu/ctr-search/search?query=MAHALE
(https://www.clinicaltrialsregister.eu/ctr-search/search?query=MAHALE) . [Last
accessed: February 2022].

 

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

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