Tezepelumab is a new drug being developed by Astra Zeneca and Amgen for severe asthma. Tezepelumab is an injectable medication, recent mid stage clinical trials showed that it reduced asthma exacerbations between 61-71% depending on the dose for severe asthmatics.
Currently there are three asthma injectable medications on the market. The most recent two that were approved are Nucala and Cinqair, these medications target IL-5 which is a major producer of eosinophils in the blood and tissues (eosinophils are responsible for airway inflammation and asthma). Tezepelumab works differently than Nucala and Cinaqair as it targets TSLP (Thymic stromal lymphopoietin). TSLP is a key regulator in asthma pathogenesis.
Tezepelumab is different because it acts further upstream in the inflammatory cascade responsible for asthma by blocking the action of a cell-signalling protein called thymic stromal lymphopoietin (TSLP).
TSLP is an epithelial cytokine produced in response to pro-inflammatory stimuli such as allergens, viruses and other pathogens in the lung. It drives the release of downstream T2 cytokines including IL-4, IL-5 and IL-13, leading to inflammation and asthma symptoms. TSLP also activates many types of cells involved in non T2 driven inflammation. Therefore, the early, upstream activity of TSLP in the inflammation cascade has been identified as a potential target across a broad asthma population.
Tezepelumab may be able to treat a wider of range of asthma patients according to Astra Zeneca’s head of respiratory. Tezelpelumab is also being developed for atopic dermatitis.
Dupilumab which is currently approved for atopic dermatitis and is currently being developed for asthma (it is now approved), had recent disappointing news for its asthma studies. In its late stage trials, it only reduced severe asthma attacks by 46%, compared with 71% in its mid stage data. It remains to be seen how Tezepelumab will do in its late stage data in the future.
There is no current brand name yet for Tezepelumab and there is no current information on pricing of Tezepelumab either. Nucala and Cinqair are both currently priced at several thousand dollars a month, so expect Tezepelumab to fall within the same price range.
If you currently suffer from severe asthma, speak to your allergy and asthma doctor to see what treatment is right for you. Nucala and Cinqair both target eosinophils, if you don’t fit that criteria speak to your doctor about what treatment options are best available. Xolair is another biological medication for severe asthma that targets IgE. This medication has been out for over 10 years and it is also used for chronic idiopathic urticaria. It remains to be seen what criteria would be needed for Tezepelumab and TSLP and if it gets FDA approval in the future.
Update March 11, 2019
A recent study published in The New England Journal of Medicine, titled “Tezepelumab in adults with uncontrolled asthma” showed that after 52 weeks of therapy, tezepelumab reduced the annualized rate of asthma exacerbations, independent of both baseline eosinophil count and other Th2 biomarkers (IgE and exhaled NO).
Tezeepelumab is a IgG2 monoclonal antibody that binds to the epithelial cell-derived cytokine TSLP. The investigators concluded “These findings highlight the potential advantages of targeting an upstream cytokine such as TSLP, which may affect disease activity more broadly than inhibition of a single downstream pathway.”
Update June 13, 2019
More studies recently published about Tezepelumab has shown that patients in placebo controlled trials, groups receiving active treatment suffered fewer exacerbations. Blood eosinophils, FENO and total serum IgE all declined during active therapy. Data from these trials of tezepelumab confirm that TSLP plays an important role in asthma and inhibition of this cytokin results in significant improvements in exacerbation rates, asthma physiology, subjective measures of asthma and T2 inflammatory and immune process. A phase 3 study of tezepelumab in adults with moderate to severe uncontrolled asthma, including patients with T2 high and T2 low asthma, is ongoing, with results expected early in 2021.
Update August 11, 2020
Amgen and AstraZeneca are getting ready to launch the medication soon, in advertising material they write ” TSLP is a key epithelial cytokine that sits at the top of the inflammatory cascade and offers a new way to think about severe asthma.” The current inflammatory markers for asthma that other biologics target are IgE and Eosinophil counts. Tezepelumab may have work for different types of asthma with possible neutrophil predominant cells.
Update February 27, 2021
“Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY” was published in Annals. It was found that Tezepelumab treatment improved patient reported outcomes vs. placebo, as indicated by the higher proportion of asthma control questionnaires (ACQ) and asthma quality of life questionnaires (AQLQ) and improvements in symptom severity in the the tezepelumab dose groups. These data provide additional evidence that blocking TSLP is an effective strategy for the treatment of severe, uncontrolled asthma and further support its use in this patient population. The PATHWAY study was a phase 2b, randomized, multicenter double-blind, placebo controlled trial. Patients were between 18-75 and had asthma that was uncontrolled despited treatment with medium or high dose inhaled steroids for 6 months before enrollment.