Earlier this month, the New England Journal of Medicine released Phase 3 clinical trial results for tezepelumab – a potential first-in-class severe asthma treatment for adults and adolescents. The findings were presented at American Thoracic Society annual meeting (ATS) May 14- 19.
DocWire News spoke with Dr. Jean-Pierre Llanos Ackert, Executive Medical Director, Inflammation Business Unit at Amgen and Dr. Chris Ambrose, Franchise Head, US BioPharmaceuticals Medical, Respiratory at AstraZeneca to discuss to discuss these promising trial data.
DocWire News: Can you talk to us about the treatment that was assessed, tezepelumab? Why and how (the study) was conducted, and what were the findings?
Dr. Chris Ambrose: Absolutely. Yeah, so thank you for the question. So the NAVIGATOR Phase 3 trial that as you mentioned, just published, it was conducted to confirm and better describe the efficacy and the safety of tezepelumab in a broad population of patients living with severe uncontrolled asthma. It was a year long randomized, double-blinded placebo controlled study. Was way of context tezepelumab is a monoclonal antibody that blocks the activity of TSLP or thymic stromal lymphopoietin. And that’s an epithelial cytokine that acts at the top of the asthma inflammation or inflammatory cascade, and has been shown to play a central role in allergic eosinophilic and even non-T2 asthma inflammation. So in the NAVIGATOR study tezepelumab demonstrated superiority across every primary and key secondary endpoint in this broad population of patients compared to placebo when added to standard of care. And standard of care was medium to high dose inhaled corticosteroids with at least one additional controller.
So overall exacerbations were reduced by 56%. And in the subgroup of patients with baseline eosinophil counts, less than 300 cells per microliter. The trial also met the primary endpoint with a statistically significant and clinically meaningful reduction in exacerbations compared to placebo. In fact, asthma exacerbation reductions were seen with tezepelumab in patients, regardless of the baseline blood eosinophil count, or the FeNO level the fractional exhaled nitric oxide level, or allergic status. And improvements were also seeing in lung function, asthma control, asthma related quality of life and asthma symptoms. Additionally, tezepelumab reduced exacerbations requiring ER visits or hospitalizations by 79% and exacerbations requiring hospitalization by 85%. And with a respect to the safety analysis, adverse events following tezepelumab were similar to placebo, 77% of patients receiving tezepelumab versus 81% of patients receiving placebo reported any adverse event and 10% of patients receiving tezepelumab versus 14% of those receiving placebo reported a serious adverse event. So overall the NAVIGATOR results demonstrate the benefit of blocking TSLP at the top of the asthma inflammatory cascade for a broad population of patients with severe uncontrolled asthma, across phenotypes and irrespective of inflammatory biomarkers.
DocWire News: Were any of the findings surprising?
Dr. Jean-Pierre Llanos-Ackert: Yeah, as Chris mentioned, what we were pleased to see in the NAVIGATOR trial is the ability of tezepelumab to reduce 85% hospitalization. The exacerbation that leads to hospitalization compared to placebo, which is very important for patients. Hospitalizations overall, reducing exacerbations is very important in the treatment of asthma, but more importantly, trying to reduce the severe exacerbation that leads to a hospitalization is critical. The hospitalization not only implies a burden for the patient and for their families, obviously for the healthcare system. And more importantly is the risk factor for mortality. So that’s something that every patient would like to avoid, obviously. And that’s why we are excited that tezepelumab may be a potential treatment option in the future to reduce exacerbations that lead to hospitalization in a broad population of severe asthma patients, irrespective of biomarker levels.
DocWire News: Did the study have any limitations?
Dr. Chris Ambrose: Well, so as I mentioned before that the NAVIGATOR study, was a large study. The Phase 3 study was randomized double-blinded placebo controlled that was conducted in 1,061 adults and adolescents. So that’s adults 18 to 80 years of age and adolescents, 12 to 17 years of age, all of whom had severe uncontrolled asthma. The patients who were receiving treatment with medium or high dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids. And they had to have two or more exacerbations in the prior year. So with regard to limitations, similar to other trials of biologics in severe asthma, the trial was limited by its duration which is 52 weeks, which is a long study, but certainly sometimes patients take these treatments for longer than a year. It had strict inclusion criteria, which again are consistent across these trials of biologics in severe asthma. But those inclusion criteria mean that we’ve excluded relevant patient subgroups such as smokers, and those with certain coexisting conditions. And also the enrollment, there was a limited number of adolescent patients compared to the number of adults enrolled in the study.
DocWire News: How big a challenge is it currently managing people in the US with severe asthma?
Dr. Jean-Pierre Llanos-Ackert: Thanks, Rob. And to explain that maybe I should highlight asthma is it heterogeneous disease, which means that there are several different factors and to give an example of viruses or allergens and all these different factors can trigger different inflammatory pathways, which will lead to increase of one or in some patients, sometimes multiple biomarkers that drive the disease and current treatment options like inhaled corticosteroid, and even the current biologics may not be able to aim all these different biomarkers. And that makes the treatment of asthma very challenging. To your question in the worldwide, it’s calculated at severe asthma patients represent 2.5 million patients and only in the U.S. Severe uncontrolled asthma patients represent 1 million of patients. These are the patients that could be eligible for a biologic. And even though it has been calculated at up to 10% of all asthma represents severe asthma. This subgroup is the one that has twice the risk of being hospitalized and represents 40 to 50% of all the asthma related health care costs.
DocWire News: What are the clinical implications of these findings?
Dr. Chris Ambrose: So yeah, so we feel the NAVIGATOR results really underscore the potential of tezepelumab to transform the treatment for a broad population of patients living with severe asthma. So today, as Dr. Llanos has mentioned due to the heterogeneous and complex nature of severe asthma a significant number of patients face debilitating symptoms, despite standard inhaled medicines, and the current biologics are only approved for select phenotypes of severe asthma, such as allergic asthma or eosinophilic asthma, the NAVIGATOR Phase 3 trial, and the previous pathway Phase 2B trial, both demonstrated the efficacy and safety of tezepelumab in a broad population of severe uncontrolled asthma patients, regardless of their phenotype or biomarker levels. So there’s now a strong body of evidence showing the benefit of targeting TSLP at the top of the inflammatory cascade in asthma with tezepelumab to benefit patients with severe uncontrolled asthma.
DocWire News: Closing thoughts?
Dr. Jean-Pierre Llanos-Ackert: Well, I may begin. I just want to share that we are so proud about the results that we have seen in the NAVIGATOR pathway. The NAVIGATOR results show that there is a benefit of targeting TSLP as the parameters set on top of the inflammatory cascade and these results support the fact that we are very excited to bring, hopefully in the future, tezepelumab as a treatment option for a broad population of severe uncontrolled asthma patients across different phenotypes then regardless of the biomarker level.
Dr. Chris Ambrose: Yeah. And I would just add in additionally, as we bring tezepelumab to market, we hope that it will give specialists and other providers an opportunity to expand the treatment options in severe asthma. Today only about 2 of 10 patients with severe uncontrolled asthma are receiving a biologic. So as a result there remains a significant unmet need to help more patients get the treatment they need to control their asthma and hopefully live their lives without the limits that asthma can impose.