Fasenra shows consistent safety and sustained efficacy in long-term Phase III BORA trial in severe eosinophilic asthma

18 September 2018
 

74% of continuously-treated patients with a blood eosinophil count of 300 or greater were exacerbation-free in the second year of treatment

Data presented at the European Respiratory Society (ERS) International Congress 2018

AstraZeneca today announced results from the BORA Phase III extension trial evaluating the long-term safety and efficacy of Fasenra (benralizumab) as an add-on maintenance treatment in patients with severe eosinophilic asthma who had previously completed one of the two pivotal SIROCCO or CALIMA Phase III trials.

In the BORA trial, Fasenra given for an additional 56 weeks showed a safety and tolerability profile similar to that observed in the placebo-controlled SIROCCO and CALIMA trials, with no increase in the frequencies of overall or serious adverse events. The improvements in efficacy measures observed with Fasenra in the SIROCCO or CALIMA trials were maintained over the second year of treatment. Patients who were treated with placebo in the SIROCCO or CALIMA trials and subsequently transitioned to Fasenra in the BORA trial experienced improvements in efficacy outcomes consistent with those observed for Fasenra-treated patients in the previous trials.¹

74% of patients with a baseline blood eosinophil count of 300 cells per μL or greater (the primary efficacy population in the Phase III trials) who received Fasenra every eight weeks continuously from SIROCCO or CALIMA and into BORA, were exacerbation-free in BORA in their second year of treatment and maintained improvements in lung function and asthma control.¹

65% and 66%, respectively, of patients with a baseline blood eosinophil count of 300 cells per μL or greater who received Fasenra 30 mg every eight weeks were exacerbation-free in their first year of treatment in the one-year, predecessor SIROCCO and CALIMA trials (49% for placebo arms in both trials).^2,3

The BORA data will be presented today during a late-breaking oral session at the European Respiratory Society (ERS) International Congress 2018 in Paris, France.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: “The BORA data are important news for patients with severe eosinophilic asthma who need a treatment with sustained efficacy to help control their disease, and with a safety profile that supports long-term use.”

Dr. William Busse, Professor of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, and lead investigator on BORA, said: “As a clinician, I am excited by the BORA trial results, which provide confidence to patients with severe eosinophilic asthma and physicians that the positive outcomes they are seeing with Fasenra can be maintained over a second year of treatment. In Fasenra, we have a biologic treatment that can improve outcomes for these patients long-term.”

The overall annual asthma exacerbation rate for patients with baseline blood eosinophil counts of 300 cells per μL or greater who received Fasenra every eight weeks continuously was consistent with the predecessor SIROCCO and CALIMA trials (0.46 in BORA; 0.65 and 0.66 in SIROCCO and CALIMA, respectively).^2,3 Overall improvements in lung function, asthma control, asthma-related and general health-related quality of life scores were maintained for patients who received Fasenra continuously and were improved for patients previously receiving placebo in SIROCCO or CALIMA.¹  Near complete eosinophil depletion was maintained in patients who continuously received Fasenra.¹

The most commonly-reported adverse events (≥ 5%) in BORA were upper respiratory tract infection, worsening asthma, headache, bronchitis and acute sinusitis.¹

Fasenra is AstraZeneca’s first respiratory biologic and is approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and several other countries.

NOTES TO EDITORS

About Severe Asthma

Asthma affects approximately 339 million individuals worldwide.^4,5 Up to 10% of asthma patients have severe asthma, which may be uncontrolled despite high doses of standard-of-care asthma controller medicines and can require the use of chronic oral corticosteroids (OCS).^6,7,8 Severe, uncontrolled asthma is debilitating and potentially fatal with patients experiencing frequent exacerbations and significant limitations on lung function and quality of life.^6,8,9,10 Severe, uncontrolled asthma has higher risk of mortality than severe asthma.⁸

Severe, uncontrolled asthma can lead to a dependence on OCS, with systemic steroid exposure potentially leading to serious short- and long-term adverse effects including weight gain, diabetes, osteoporosis, glaucoma, anxiety, depression, cardiovascular disease and immunosuppression.^11,12,13,14 There is also a significant physical and socio-economic burden of severe, uncontrolled asthma with these patients accounting for 50% of asthma-related costs despite compromising only 10% of the asthma population.^7,15

Clinical features associated with an eosinophilic phenotype that can act as markers for enhanced efficacy with targeted therapy in severe eosinophilic asthma include: greater baseline blood eosinophil counts, a history of more frequent exacerbations, chronic OCS use and a history of nasal polyposis.^8,16

About Fasenra

Fasenra is a monoclonal antibody that binds directly to the IL-5α receptor on eosinophils, and attracts natural killer cells to induce rapid and near-complete depletion of eosinophils via apoptosis (programmed cell death).^17,18 Eosinophils are a type of white blood cell that are a normal part of the body's immune system and elevated levels of eosinophils are seen in about half of severe asthma patients.^9,19 Elevated levels of eosinophils impact airway inflammation and airway hyper-responsiveness, resulting in increased asthma severity and symptoms, decreased lung function and increased risk of exacerbations.^7,9

Fasenra is AstraZeneca’s first respiratory biologic, now approved as an add-on treatment in severe eosinophilic asthma in the US, EU, Japan, and several other countries, and under regulatory review in several other jurisdictions. Where approved, Fasenra is available as a fixed-dose subcutaneous injection via a prefilled syringe administered once every four weeks for the first three doses, and then once every eight weeks thereafter.²⁰ Fasenra is also being studied in severe nasal polyposis.

Fasenra was developed by AstraZeneca with MedImmune, the company’s global biologics research and development arm, and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Hakko Kirin Co., Ltd., Japan.

About the BORA Trial

BORA is one of the six Phase III trials in the Fasenra WINDWARD programme in asthma, which also includes SIROCCO, CALIMA, ZONDA, BISE and GREGALE. BORA is a randomised, double-blind, parallel-group, Phase III extension trial of patients who had completed one of the three pivotal Phase III trials, SIROCCO, CALIMA or ZONDA.²¹ The current analysis includes results for 1926 patients from the two placebo-controlled exacerbation trials, SIROCCO (48 week) and CALIMA (56 week). Patients continued add-on treatment with subcutaneous Fasenra 30 mg every four weeks (Q4W) or every eight weeks (Q8W; first three doses four weeks apart) or, for patients previously receiving placebo, were re-randomised 1:1 to either Q4W or Q8W.

Once the BORA target enrolment had been achieved, adult patients who wanted to continue treatment for a longer period of time had the option to continue therapy in an additional open-label, long term extension trial, without completing the full, planned follow up in BORA. Approximately half of patients in the shorter (28 weeks) and smaller ZONDA study went into an additional extension trial without completing the planned 56-week treatment period in BORA. Therefore, ZONDA patients were not included in this BORA analysis, and will be reported separately according to the analysis plan.

Additional analyses from the BORA trial, including treatment in adolescents up to 108 weeks, will be available in the second half of 2019.

About AstraZeneca in Respiratory Disease

Respiratory disease is one of AstraZeneca’s main therapy areas, and the Company has a growing portfolio of medicines that reached more than 18 million patients in 2017. AstraZeneca’s aim is to transform asthma and COPD treatment through inhaled combinations at the core of care, biologics for the unmet needs of specific patient populations, and scientific advancements in disease modification.

The Company is building on a 40-year heritage in respiratory disease and AstraZeneca’s capability in inhalation technology spans pressurised metered-dose inhalers and dry powder inhalers, as well as the Aerosphere Delivery Technology. The Company also has a growing portfolio of respiratory biologics including Fasenra (anti-eosinophil, anti-IL-5rɑ), now approved for severe eosinophilic asthma and in development for severe nasal polyposis, and tezepelumab (anti-TSLP), which is in Phase III trials and achieved its Phase IIb primary and secondary endpoints. AstraZeneca’s research is focused on addressing underlying disease drivers focusing on the lung epithelium, lung immunity and lung regeneration.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

For more information, please visit www.astrazeneca.com and follow us on Twitter @AstraZeneca.

CONTACTS

References

1.     Busse WW, Bleeker ER, Fitzgerald JM, Ferguson GT, Barker P. Long-term Safety and Efficacy of Benralizumab in Severe, Uncontrolled Asthma: First Results of BORA, a Randomized, Phase III Extension Study. ERS Oral. 2018

2.     Bleecker ER, Fitzgerald MJ, Chanez P, 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. Volume 388, Issue 10056, 2115 – 2127.

3.     FitzGerald MJ, Bleecker E, Nair P, et al. Benralizumab, an anti-interleukin-5 receptor α 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. Volume 388, Issue 10056, 2128 – 2141.

4.     Chanez P, Humbert M. European respiratory review: Asthma: still a promising future? European Respiratory Review. 2014, 23 (134) 405-407.

5.     The Global Asthma Network. The Global Asthma Report 2018. [Online]. Available at: http://www.globalasthmanetwork.org/publications/Global_Asthma_Report_2018.pdf. Last accessed: September 2018.

6.     Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014; 43: 343–73.

7.     Wenzel, Severe Asthma in Adults. Am J Respir Crit Care Med. 2005; 172 VOL 172; 149–160, 2005.

8.     Peters SP, Ferguson G, Deniz Y, et al. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med 2006: 100(7):1139-51.

9.     Zhang, JY and Wenzel, SE. Tissue and BAL based biomarkers in asthma. Immunol Allergy Clin North Am. 2007; 27: 623–632 (vi.).

10.  Fernandes AG, Souza-Machado C, Coelho RC et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014; 40(4): 364-372.

11.  Sweeney J, et al. Thorax 2016;71:339–346

12.  Hyland ME et al. Qual Life Res. 2016; 24:631-639

13.  Hyland ME, Whalley B, Jones RC, et al. A qualitative study of the impact of severe asthma and its treatment showing that treatment burden is neglected in existing asthma assessment scales. Quality of Life Research. 2015: 24 (3) 631-619

14.  Zeiger RS et al. J Allergy Clin Immunol Pract 2017;5:1050–1060;

15.  World Allergy Organization (WAO). The management of severe asthma: economic analysis of the cost of treatments for severe asthma. Available from: http://www.worldallergy.org/educational_programs/world_allergy_forum/anaheim2005/blaiss.php. Last accessed April 2018.

16.  Price D, Fletcher M, van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med 2014; 12; 24: 14009.

17.  Kolbeck R, Kozhich A, Koike M, et al. MEDI-563, a humanized anti–IL-5 receptor a mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010 Jun;125(6):1344-1353.e2.

18.  Pham TH, Damera G, Newbold P, Ranade K. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016; 111:21-29.

19.  Mukherjee M, Sehmi R, Nair P. Anti-IL5 therapy for asthma and beyond. World Allergy Organ J. 2014;7:32

20.  FASENRA Prescribing Information. AstraZeneca Pharmaceuticals LP.

21.  A Safety Extension Study to Evaluate the Safety and Tolerability of Benralizumab (MEDI-563) in Asthmatic Adults and Adolescents on Inhaled Corticosteroid Plus LABA (BORA). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02258542. Accessed August 24, 2018.