First patients enrolled in Phase IIIb PONENTE trial evaluating the elimination of oral corticosteroids with Fasenra in severe eosinophilic asthma

PONENTE builds on Phase III ZONDA trial by evaluating a larger number of severe eosinophilic asthma patients and a faster rate of reduction of OCS than previously studied
 

18 September 2018

AstraZeneca today announced that the first patients have been enrolled in the Phase IIIb PONENTE trial that will further investigate the potential of Fasenra (benralizumab) to eliminate maintenance oral corticosteroid (OCS) use in patients with severe refractory eosinophilic asthma.                                                                                

The PONENTE trial will evaluate the safety and effectiveness of eliminating OCS use following add-on treatment with Fasenra in approximately 600 patients with severe refractory eosinophilic asthma who require maintenance OCS (≥ 5 mg prednisone equivalent daily) to maintain control of their asthma symptoms.1 The primary outcome measures of the trial are proportion of patients achieving a 100% reduction in daily OCS dose and reduction of daily OCS use to less than or equal to 5 mg, both sustained over greater than or equal to 4 weeks without worsening of asthma.1 Trial completion is anticipated in 2020.

Fasenra has previously been shown to allow the reduction or discontinuation of OCS while maintaining asthma control, compared to placebo, when added to standard of care therapy in the Phase III ZONDA trial.2 The PONENTE trial differs from previous trials in that patients can start from higher OCS doses and the rate of reduction is faster. The durability of any observed reduction will be assessed during a minimum 24-week maintenance period.

Professor Andrew Menzies-Gow, Consultant in Respiratory Medicine and Director, Lung Division, Royal Brompton Hospital, London, the principle investigator of the trial said: “Too many patients with severe asthma suffer poor outcomes and serious adverse effects from long-term OCS treatment. PONENTE has the potential to be a landmark study based on its unique design and projected sample size, and the data should help physicians better manage their patients with severe eosinophilic asthma and adopt OCS-sparing strategies where appropriate.”

Alex de Giorgio Miller, Respiratory Vice President, Global Medical Affairs, AstraZeneca, said, “We have initiated the PONENTE trial to answer key questions that could enable physicians to reduce or even eliminate long-term OCS use among more patients, more quickly than previously assessed. The trial reflects AstraZeneca’s commitment to further strengthening the clinical profile of Fasenra, our first respiratory biologic, and supporting advancements in severe asthma care.”

More than 40% of severe asthma patients rely on frequent or maintenance use of OCS.3 Systemic OCS exposure is associated with short- and long-term adverse effects, including osteoporosis, pneumonia, cardiovascular disease, cataract, anxiety/depression, diabetes and weight gain.4,5,6 63% of patients with uncontrolled asthma used at least one course of an OCS over a 1-year period.7 Dependence on OCS is one of several characteristics associated with an eosinophilic phenotype which can act as markers to support targeted therapy in severe eosinophilic asthma.8

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

Notes to Editors

About the PONENTE Trial

PONENTE is a multicentre, open-label Phase IIIb efficacy and safety trial of Fasenra 30 mg administered subcutaneously (SC) to reduce OCS use in adult patients with severe eosinophilic asthma on high-dose inhaled corticosteroids (ICS) plus long-acting beta2-agonist (LABA) and long-term use of OCS therapy with or without additional asthma controller(s).1 The primary outcome measures of the trial are proportion of patients achieving a 100% reduction in daily OCS dose and reduction of daily OCS use to ≤5 mg, both sustained over ≥4 weeks without worsening of asthma.1

Compared to ZONDA, PONENTE will evaluate the ability to taper OCS faster and from higher doses and will assess adrenal function as part of decision-making to manage the risk of adrenocortical suppression. As it is a longer treatment duration trial, PONENTE will assess the durability of OCS reduction.

PONENTE will recruit approximately 600 patients from across 190 participating study centres, located in Europe, North America, South America and Taiwan.1

About Severe Asthma

Asthma affects approximately 339 million individuals worldwide.9,10 Approximately 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 long-term use of OCS.9,11,12 Severe, uncontrolled asthma is debilitating and potentially fatal with patients experiencing frequent exacerbations and significant limitations on lung function and quality of life. Severe, uncontrolled asthma has higher risk of mortality than severe asthma.11,12,13,14

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).15,16 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.13,17 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.9,13

Fasenra is AstraZeneca’s first respiratory biologic, now approved as an add-on maintenance 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 4 weeks for the first 3 doses, and then once every 8 weeks thereafter.18 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 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 achieved its Phase IIb primary and secondary endpoints and is continuing development in the Phase III PATHFINDER clinical trial programme. 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.
 

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References

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8.     FitzGerald JM, Bleecker ER, Menzies-Gow A, Zangrilli JG, Hirsch I, Metcalfe P, Newbold P, Goldman M. Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies. Lancet Respir Med. 2017 Sep 11.

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

10.  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.

11.  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.

12.  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.

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

14.  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.

15.  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.

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

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

18.  FASENRA Prescribing Information. AstraZeneca Pharmaceuticals LP.