FDA Approved Agent Omalizumab for Asthma

Transcript:

Stanley Goldstein, MD: Let’s now get into the discussion about the specific biologics. We’ve heard terms that we’ve been throwing out already; omalizumab, mepolizumab, benralizumab, reslizumab, dupilumab. What are some of these differences? Let me first address, I think, Giselle, you already started to address omalizumab, the treatment of omalizumab. What does that do? We know omalizumab is the only biologic that targets and blocks IgE, as you already mentioned, Giselle. By blocking IgE, what happens physiologically, is that you have a downregulation of the high-affinity IgE receptors. They that are sitting on inflammatory cells such as mast cells, basophils, including dendritic cells, and that will result in thea prevention of cross leaking of IgE antibodies, therefore limiting degranulation and limiting the media(?) as it’s being released. It’s actually been addressed in the literature as far as omalizumab does havehaving anti-inflammatory effects in asthma.

As a matter of fact, there was an article in early 2000s by Ducanovic(?). He wrote an article on what is actually going on by looking at patients, and doing biopsy, y and looking at sputum eosinophils, andeosinophils. showed that omalizumab also will result in; Tthey had the patients whothat were in the study on uncontrolled asthma, had 2% of sputum eosinophils or greater. After treating them with omalizumab, he did showed that there was a statistical reduction in eosinophils in the sputum, and also eosinophils in the tissue. So, there’s an overlap between allergic and eosinophilic asthma.

When you think about eosinophils in allergic asthma, eosinophils still play a major role in allergic asthma. If you look at the demographic data of patients in the two pivotal trials in omalizumab, you find that the mean value of eosinophils in these patients were on the order of in the low 300s, and you find that also in post-hoc analyses, you can look at; to understand the pivotal trials in omalizumab, you can think about that those patients were not enriched patients in any way. They weren’t enriched upon their eosinophils,eosinophils; they weren’t enriched as far as their pheno.

I don’t think we even knew what pheno was then, like 20 years ago. So theyThey weren’t an enriched patient population. But if you doubt, what they’ve done is they’ve taken those studies and looked at a post-hoc analysis and what happens if you enrich that patient population based upon their eosinophils. Ananear(?) showed that if you look at those patients in the omalizumab trials, looking at exacerbations, you find that those patients who had an eosinophil count of greater than 300 versus lower than 300, had a better response as far as decrease in exacerbations. Those patients who had eosinophils below 300 also had a good response, but it was better with higher eosinophil counts.

And then Tom Casale, good old friend Tom, did a post-hoc analysis on looking at the patients in those two pivotal trials that were done for the registration of omalizumab. He spread out and looked at the eosinophil counts from below 200 up into the order of greater than 400, and there was a gradual increase in the reduction of exacerbations; where overall, if you look at the reductions of exacerbations with omalizumab, it’s in the order around 53%. But, when you enrich that patient population by looking at the eosinophils, in those patients who have eosinophil counts of greater than 400, you can enrich that by a reduction in exacerbation rates by 73%. 

[46:58]

Now, something important that gets misconstrued in with the physicians that who treat biologics, when you look at total, and when you’re thinking about allergic asthma, we can talk about total IgE and we can think about specific IgE. Total IgE doesn’t tell us anything about that patient, whether they are highly allergic or not allergic. It’s just a way of dosing omalizumab because you’re dosing it based upon the total amount of IgE. When you give a first dose of omalizumab, within 24 hours you’re reducing that specific IgE by 96%. That’s a significant number because that’s what results in the decrease in the high-affinity IgE receptors.

When you’re thinking about allergic asthma, andasthma and defining what do you mean by ‘allergic asthma’ and who’s what’s right for that patient with omalizumab, you want to know that these patients have perennial allergens that are associated with the worsening of their disease, their exposure. That’s why when you’re looking at to define whether they need it, you’re looking at specific IgE. So it’s specific IgE to determine whether a person needs omalizumab, and it’s total IgE and the weight as far as dosing of omalizumab.

Transcript Edited for Clarity