Late last year Amgen and AstraZeneca reported that their investigational treatment tezepelumab (a potential first-in-class TSLP inhibitor) missed the primary endpoint of the Phase III SOURCE trial by failing to demonstrate a significant reduction in the daily amount of oral corticosteroids (OCS) needed by certain patients with severe asthma, compared to placebo.
This came as something of a surprise. In November, Amgen and AstraZeneca confirmed that tezepelumab had met its primary endpoint in the Phase III NAVIGATOR study by demonstrating a significant and clinically meaningful reduction in the annualised asthma exacerbation rate (AAER) over 52 weeks compared to placebo plus standard care.
Furthermore, in NAVIGATOR top-line data supports efficacy in a broad range of patients regardless of severe asthma phenotype, including those with low blood eosinophil counts. This, in conjunction with tezepelumab’s novel mechanism of action, could differentiate Amgen and AstraZeneca’s product in the increasingly crowded market of biologic asthma therapies.
In November we ran a short survey to pulmonologists to benchmark what detailed results from NAVIGATOR could be required to drive adoption of tezepelumab assuming it is approved by regulators. More here
AstraZeneca has suggested study design could have adversely impacted the outcome of the SOURCE trial and Amgen, speaking at the JP Morgan Healthcare Conference this week, said they remain very confident that tezepelumab will become established as a differentiated and valuable treatment option for severe asthma.
We are running a second short survey to see if pulmonologists in five key markets (France, Germany, Italy, Spain, UK and the US) agree. We will publish the results next week. Specifically we are asking…
Q. Tezepelumab is a potential first-in-class TSLP inhibitor being developed for the treatment of severe asthma. In the Phase III NAVIGATOR study tezepelumab was shown to demonstrate statistically significant and clinically meaningful reductions in the annualised asthma exacerbation rate (AAER) across a broad spectrum of patients, including those with baseline eosinophil counts of less than 300 cells/mcL and those with baseline eosinophil counts of less than 150 cells/mcL.
Although detailed results from this study have yet to be presented, do you think broad AAER reductions including patients with lower baseline eosinophil counts will positively differentiate tezepelumab from other biologic therapies approved to treat severe asthma?
1 – No 2 3 4 – Moderate differentiation 5 6 7 – Significant differentiation
Q. A previous survey of pulmonologists we ran suggested that tezepelumab will need to demonstrate a 40-50% reduction in annualised asthma exacerbation rate (AAER) in patients with baseline eosinophil counts of less than 150 cells/mcL in order to dive adoption as a routinely used medication. Do you agree with this assessment?
No – A lower than 40% reduction would drive routine use
No – A higher than 50% reduction is required to drive routine use
Q. In a second Phase III study, tezepelumab failed to significantly reduce the daily amount of oral corticosteroids (OCS) needed by certain patients with severe asthma, compared with placebo.
The SOURCE study enrolled 150 adults with severe asthma who require continuous treatment with inhaled corticosteroids (ICS) plus long-acting beta2-agonists (LABA), and chronic treatment with maintenance OCS therapy. Study participants were randomised to receive tezepelumab every four weeks or placebo on top of standard care, with patients maintained on their currently prescribed ICS plus LABA, with or without other asthma controller therapy.
The main outcome measure was the percentage reduction from baseline in the prescribed daily OCS maintenance dose at 48 weeks, while not losing asthma control.
Thinking about the potential role of tezepelumab as a new treatment for a broad population of severe asthma patients, how concerned are you about its failure to significantly reduce the number of required OCS in this study?
1 – Not concerned 2 3 4 – Moderately concerned 5 6 7 – Significantly concerned
Q. Is the potential impact of this study’s primary endpoint (failure of tezepelumab to significantly reduce the daily amount of oral corticosteroids (OCS) needed by certain patients with severe asthma compared with placebo) limited by a real-world decline in the number of severe asthma patients who are being chronically treated with steroids?
Q. Tezepelumab’s developers aim to submit regulatory applications this year based on the successful NAVIGATOR study.
They have played down its failure to reduce oral corticosteroid use in the SOURCE study and have suggested that tezepelumab’s differentiation lies in its ability to work regardless severe asthma phenotype, including those with low blood eosinophil counts, as well as its unique mechanism of action.
Do you agree with this assessment of tezepelumab’s broad clinical profile?
Results and related analysis will shortly be published for FirstWord Pharma PLUS subscribers to read, with the opportunity for non-FirstWord Pharma PLUS subscribers to purchase these findings. To be notified when poll results and analysis become available, please click here
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