Severe Uncontrolled Asthma Highlights
12 May, 2021 | DelveInsight
- Tezspire is the only biologic approved for severe asthma with no phenotype (e.g. eosinophilic or allergic) or biomarker limitation
- Tezspire helps in stopping inflammation at the source and has the potential to treat a broad population of severe asthmatic patients
Thymic stromal lymphopoietin (TSLP), which was primarily identified in 1994 as a cytokine produced by thymic stromal cells, a short-chain four α-helical bundle type I interleukin-2 (IL-2) family cytokine shares its homology with IL-7. It was observed to be quite similar to IL-25 and IL-33. Its ability to differentiate naïve CD4+ T lymphocytes in type 2 cells, produce IL-4, IL-5, IL-13, and reduce the expression of interferon γ (IFN-γ) related to type 1 cells is well known. The expression of TSLP increases in the asthmatic airways and correlates with the expression of type 2-attracting chemokines and the severity of the disease.
In December 2021, AstraZeneca and Amgen’s Tezspire/tezepelumab got approval by the USA FDA as an add-on therapy for the treatment of patients affected with severe asthma. According to DelveInsight’s estimations, there were nearly 11,603,000 and 42,613,000 diagnosed prevalent cases of Paediatric and adult asthma, respectively in the 7MM [the US, EU-5 (Germany, France, Italy, Spain and the UK), and Japan] in the year 2021 which are further expected to increase at a significant CAGR in the future years. Out of total diagnosed prevalent cases, 5,101,270 were of severe form in the 7MM in 2021.
Tezspire acts at the top of the inflammatory cascade by targeting TSLP and was approved following a Priority Review by the USA FDA and based on the results from the PATHFINDER clinical trial program. The application included results from the pivotal NAVIGATOR Phase III trial in which Tezspire demonstrated dominance across every primary and key secondary endpoint in patients with severe asthma compared with placebo while adding to standard therapy.
Furthermore, it is the first and only biologic to consistently and significantly reduce 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). It is the only biologic approved for severe asthma with no phenotype (e.g. eosinophilic or allergic) or biomarker limitation within its approved label.
“The essential function of TSLP in immunological homeostasis and modulating inflammatory responses at mucosal barriers may explain why tezepelumab is so effective in treating severe uncontrolled asthma”
In May 2022, the data presented at the American Thoracic Society (ATS) International Conference 2022 showed based on a study that patients with severe, uncontrolled asthma demonstrated a higher proportion of substantial clinical responses to tezepelumab. The study uses data from the completed phase III, double-blind, placebo-controlled NAVIGATOR trial to conduct an on-treatment analysis of responses to tezepelumab (NCT03347279).
In the analysis, 51% of the patients received tezepelumab vs. placebo. Across response criteria, the proportion of responders was higher in the tezepelumab as compared with the placebo group for exacerbation reduction i.e. 85.4% vs. 67.5%; Asthma Control Questionnaire (ACQ)-6 total score (86.9% vs. 76.6%); an improvement from baseline pre-bronchodilator forced expiratory volume in one second (FEV1) i.e. 60.3% vs. 49.9%; and in Clinical Global Impression of Change (CGI-C) score (81.5% vs. 67.7%). The proportion of complete responders (those who achieved significant improvement on all measures) in the tezepelumab group as compared with the placebo cohort was double.
New novel approaches that are capable of blocking TSLP such as fully human single-chain fragment variables against TSLP, bi-functional drugs that combine anti-IL-13 monoclonal antibodies with an anti-TSLP mAb, a fusion protein consisting of the ectodomains of TSLPR and IL-7Ra that extend into the extracellular space which is also known as a TSLP-trap, fragments capable of upsetting the TSLP/TSLPR complex are also expected to enter the market. Some assets are under preclinical investigation e.g. Zweimab (monovalent bispecific) and Doppelmab (bivalent bispecific) which are novel highly potent bispecific anti-TSLP/IL13 antibodies. It has also been observed that Zweimab and Doppelmab have a stronger affinity to the human targets compared to parental antibody formats.
Both TSLP and IL-13 have arisen as important players in cellular signalling in asthma which is categorized by Th2 inflammation. According to DelveInsights’s analysis of the Severe Asthma market, Tezespire is expected to reach sales close to USD 2Bn for the 7 major markets by 2032. So far biological treatments appear to be a more preferred long-term treatment against type 2 inflammation in severe asthma to reduce OCS exposure. Although there have been no head-to-head comparisons of biologic medicines for asthma to date, the findings of these studies imply that tezepelumab is as effective as other treatments at reducing exacerbations.
For more detailed analysis, visit Severe Asthma market