DocWire News recently spoke with Chris Ambrose, MD, MBA, Franchise Head, US BioPharmaceuticals Medical, Respiratory at AstraZeneca, and Jean Pierre Llanos Ackert, Executive Medical Director, Global Medical Affairs Lead – Tezepelumab & Pulmonary Pipeline at Amgen. We discussed the NAVIGATOR study, which demonstrated the robust efficacy of tezepelumab in treating people with severe uncontrolled asthma. See what they had to say.
DocWire News: Can you provide us with an overview of the NAVIGATOR study?
Dr. Chris Ambrose: NAVIGATOR was a year long pivotal phase III trial that evaluated the effect of Tezepelumab in a broad population of patients living with severe uncontrolled asthma. And we included in the study the range of severe asthma phenotypes. Those with eosinophilic and non-eosinophilic disease and allergic and non-allergic disease. Tezepelumab is a monoclonal antibody that blocks the activity of TSLP or thymic stromal lymphopoietin, which is an epithelial cytokine that acts at the top of the asthma inflammatory cascade and has been shown to play a central role in allergic and eosinophilic inflammation, as we well as airway hyperresponsiveness. In the NAVIGATOR results that were published in The New England Journal of Medicine, Tezepelumab demonstrated a statistically significant 56% reduction in exacerbations compared to placebo in patients with severe asthma. But, importantly, with a 41% reduction in those with blood eosinophil counts less than 300 cells per micro liter. And on the flip side, 70% reduction in those with blood eosinophil counts greater than an equal to 300 cells per microliter.
And, in fact, asthma exacerbation reductions were seen with Tezepelumab in patients, regardless of baseline blood eosinophil count, their FeNO level, or fractional exhaled nitric oxide, or allergic status. And then, when we looked at events that required more significant medical attention, such as those requiring ER visits or urgent care or hospitalization, we saw a 79% reduction with Tezepelumab. Improvements were also seen with lung function, with asthma symptoms, asthma control, and asthma related quality of life. And, in safety analyses, adverse events following Tezepelumab were similar to placebo. 77% of patients receiving Tezepelumab versus 81% receiving placebo reported any adverse event. And, with serious adverse events, it was 10% of patients receiving Tezepelumab versus 14% of patients receiving placebo.
Were the results surprising?
Jean Pierre Llanos Ackert: Well, no. The results were not surprising to us because in NAVIGATOR we had seen already improvement that the lung function improved early on. The first measurement, where we did lung function testing with traditional spirometry NAVIGATOR, the first measurement was at two weeks. There, we saw an improvement in FEV1. But we had no earlier measurement so we didn’t know if, prior to that two week time point, maybe the lung function improved in these patients. So, in this analysis that we have shown in CHEST, we use a different method, which is the peak flow meter. It’s a simple test that the patients can do at home. It assesses how fast and how well the patients can blow out the air. That is what it is impaired in the patients with asthma. And they had a simple device that they could use every day at home, measure in the morning, measuring at night, every day.
And so that allowed us to look even earlier than that two week time point, if that improved. And we did a weekly average of all those measurements that they did at home and could identify that, as early as one week, the peak flow had already improved on those patients. And definitely this is important to highlight because patients want to feel better and blowing out air is impaired in asthma. So, to identify that these patients could improve the peak flow as early as one week, may potentially imply in some patients that they could breathe better early on. And, obviously, reinforcing, as Chris said, that by targeted TSLP on top of the inflammatory cascade, we were proving with this that these patients could have a clinical benefit with it.
Did the study have any limitations?
Dr. Ambrose: So, with regard to limitations, not particularly. It’s easy for a patient to measure the peak flow. As JP mentioned, simply by blowing hard and fast into the device. This can vary patient to patient depending on their effort, et cetera. But the studies are randomized, double blind, placebo control comparison. So those differences between patients are going to balance themselves out in the results of what we saw. And I think that’s one of the big strengths of this analysis. And, as JP mentioned, it was really impressive to see that we saw a difference in peak flow, both in the morning and evening, as early as week one. And it actually steadily improved through week five. And, after that, it plateaued and remained steady through the end of the study.
What are the clinical implications of the NAVIGATOR study findings?
Llanos Ackert: The clinical implications are that really with this we are proving that there is a potential treatment option for patients, not only to improve their symptoms, to reduce exacerbation, as Chris already summarized very well from the NAVIGATOR trial. But then, on top of that, also adding that lung function improvement and that ability to breathe better. And as early as one week, in the scenario where these patients have had a disease for many, many years, to have the ability with these treatment options to feel better or have an objective measurement that improves early on is something that definitely will benefit many patients and obviously treating physicians for those patients that still, until now, remain uncontrolled and don’t have any treatment option that can improve that.
Any closing thoughts?
Dr. Ambrose: No. Actually, I think we’ve covered it very well. Again, presenting this additional analysis at CHEST of the peak expiratory flow in the Tezepelumab versus placebo group, really just built on what we knew from NAVIGATOR. From the primary results we had already seen, as JP mentioned, the lung function improvements by FEV1, as early as week two. And now we see these differences with peak flow as early as week one and this steady improvement, in both the morning and evening time, which just gives us more faith in the ability of Tezepelumab to improve outcomes for patients living with severe uncontrolled asthma.