Tezepelumab Granted Breakthrough Therapy Designation By US FDA For The Treatment Of Patients With Severe Asthma Without An Eosinophilic Phenotype
THOUSAND OAKS, Calif., Sept. 6, 2018
THOUSAND OAKS, Calif., Sept. 6, 2018 /PRNewswire/ -- Amgen (NASDAQ: AMGN) and AstraZeneca (NYSE: AZN) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for tezepelumab in patients with severe asthma without an eosinophilic phenotype.
A Breakthrough Therapy Designation is designed to expedite the development and regulatory review of medicines that are intended to treat a serious condition and that have shown encouraging early clinical results which may demonstrate substantial improvement on a clinically-significant endpoint over available medicines.
The Breakthrough Therapy Designation is supported by the tezepelumab Phase 2b PATHWAY data. The trial showed a significant reduction in the annual asthma exacerbation rate compared with placebo in a broad population of severe asthma patients independent of baseline blood eosinophil count or other type 2 (T2) inflammatory biomarkers. Currently available biologic therapies only target T2 driven inflammation. Tezepelumab is a potential first-in-class new medicine that blocks thymic stromal lymphopoietin (TSLP) – an upstream modulator of multiple inflammatory pathways.
"The Phase 2b PATHWAY trial data demonstrated tezepelumab's promise as a novel therapeutic option for a broad population of patients with severe asthma, including those ineligible for currently approved biologic therapies," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "The Breakthrough Designation will give us the opportunity to work closely with the FDA to bring tezepelumab to patients as quickly as possible."
Tezepelumab is currently in development in the Phase 3 PATHFINDER clinical trial program.
About Severe Asthma
Asthma affects 334 million people worldwide1, and up to 10 percent 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).2-4 Severe uncontrolled asthma is debilitating with patients experiencing frequent exacerbations and significant limitations on lung function.5,6
Multiple inflammatory pathways are involved in the pathogenesis of asthma.7 T2 inflammation-driven asthma, which includes eosinophilic phenotype, is present in over two-thirds of patients with severe asthma and is typically characterized by elevated levels of T2 inflammatory biomarkers, including blood eosinophils, serum IgE and fractional exhaled nitric oxide (FeNO).8,9 Conversely, approximately one-third of patients with severe asthma do not present with increased T2 inflammation.10
Tezepelumab is a potential first-in-class medicine blocking TSLP, an epithelial cytokine, critical in the initiation and persistence of airway inflammation. Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells resulting in the prevention of asthma exacerbations and improved asthma control. Due to its activity early in the inflammation cascade, tezepelumab may be suitable for a broad population of patients with severe, uncontrolled asthma irrespective of patient phenotype or T2 biomarker status. Tezepelumab is being developed by AstraZeneca in collaboration with Amgen.
About the PATHWAY Phase 2b Trial
The PATHWAY Phase 2b data were published in the New England Journal of Medicine and presented at the European Respiratory Society International Congress in September 2017. The trial evaluated the efficacy and safety of three dose regimens of tezepelumab as an add-on therapy in patients with a history of asthma exacerbations and uncontrolled asthma receiving inhaled corticosteroids/long-acting beta-agonist with or without oral corticosteroids and additional asthma controllers versus placebo. The trial showed annual asthma exacerbation rate reductions of 62 percent, 71 percent and 66 percent in the tezepelumab arms receiving either 70 mg or 210 mg every four weeks or 280 mg every two weeks compared to placebo (p<0.001 for all comparisons), respectively. These results were observed independent of baseline blood eosinophil count or other T2 inflammatory biomarkers. The most common adverse events were asthma-related, nasopharyngitis, headaches and bronchitis.
About the PATHFINDER Program
Building on the Phase 2b PATHWAY trial, the Phase 3 PATHFINDER program was initiated in the fourth quarter of 2017 with two pivotal trials NAVIGATOR and SOURCE. The program includes additional planned mechanistic and long-term safety trials.
NAVIGATOR is a Phase 3 multicenter, randomized, double-blinded, parallel-group, placebo-controlled trial designed to evaluate the efficacy and safety of a regular, subcutaneous administration of tezepelumab for 52 weeks in adult and adolescent patients with severe asthma inadequately controlled despite treatment with inhaled corticosteroid (ICS) plus one additional asthma controller medication.
SOURCE is a Phase 3 multicenter, randomized, double-blinded, parallel-group, placebo-controlled trial for 48 weeks in adult patients with severe asthma who require continuous treatment with ICS plus long-acting beta-agonist (LABA), and chronic treatment with maintenance oral corticosteroid (OCS) therapy.
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Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
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CONTACT: Amgen, Thousand Oaks
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- The Global Asthma Network. The Global Asthma Report 2014. [Online]. Available at: http://www.globalasthmanetwork.org/publications/Global_Asthma_Report_2014.pdf [Last accessed 07 August 2018].
- 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; 24: 14009.
- World Allergy Organization. The management of severe asthma: economic analysis of the cost of treatments for severe asthma 2013. http://www.worldallergy.org/educational_programs/world_allergy_forum/anaheim2005/blaiss.php (accessed 10 July 2017).
- Adelphi real world respiratory disease specific programme. [Asthma patient data file]. Bollington, UK. Uncited raw data, cited with permission 2011–2014.
- 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.
- 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.
- Gauvreau GM, O'Byrne PM, Boulet LP, et al. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N Engl J Med 2014;370:2102–10.
- Shaw DE, Sousa AR, Fowler SJ, et al. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. Eur Respir J 2015; 46(5): 1308–21.
- Fahy JV. Type 2 inflammation in asthma--present in most, absent in many. Nat Rev Immunol 2015; 15(1): 57–65.
- Fajt ML, Wenzel SE. Development of New Therapies for Severe Asthma. Allergy Asthma Immunol Res 2017; 9(1): 3–14.
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