Horizon recently received an updated indication for TEPEZZA to specify its use in patients with TED, regardless of disease activity or duration, coming after the company released positive topline results from the phase four clinical trial of patients with chronic TED.
Editor’s note: This transcript has been edited for clarity.
I'm David Hutton of Ophthalmology Times. Horizon recently received an updated indication for TEPEZZA to specify its use in patients with TED, regardless of disease activity or duration. The update comes on the heels of the company's release of the positive topline results from the phase four clinical trial of patients with chronic TED.
I am joined today by Prem Subramanian, MD, PhD, who was a trial investigator to discuss the chronic data and the new indication. Thanks for joining us, I'd like to hear a little bit about the study itself and what the results tell us.
Thanks, David. This study was a double-masked randomized placebo controlled trial of the use of TEPEZZA in patients with a much longer duration of thyroid eye disease than those who are enrolled in the phase 2 and phase 3 studies that lead to FDA approval.
Patients had to have had their thyroid eye disease for anywhere from 2 to 10 years prior to enrollment in the study. Additionally, they had to have a very low disease activity evidence as measured by the CAS the clinical activity scale score. So, their score had to be zero or 1, and that stands in contrast to the phase 2 and phase 3 studies where they had to have a cis of four or greater, and they had to have had their disease for less than 9 months. So, a significantly different patient population. and so the results of this study were, the primary outcome was similar to those prior studies where proptosis improvement over the course of the trial was considered the primary outcome. and that was measured at 6 months from trial enrollment at the end of their treatment with either placebo or with the drug.
Again, it was double masked, so as investigators we didn't know what the patients received. What the top-line data show is that the patients who received to TEPEZZA had about a 2.5 millimeter reduction in their proptosis in the study eye, which was defined either as the eye with more proptosis, or if there was equal proptosis, one was randomly chosen. That compares to placebo, where it was a less than 1 millimeter improvement. So that was the primary outcome and it was statistically significant between the 2 groups.
How important is it to receive the updated indication regardless of disease, activity, or duration?
Right. So what you're alluding to is that the FDA recently updated the label of to TEPEZZA from being just thyroid eye disease to saying thyroid eye disease, regardless of disease activity or duration of disease. That's important because some insurers, and some doctors even, perhaps had felt that the use of this drug should be limited to patients who were more like those in the clinical trials, a shorter duration of disease high CAS.
But there has been evidence that has accumulated in terms of case series and case reports that suggested that clinical benefit could be had from treating patients who didn't quite fit into that category, with TEPEZZA. And so the updated label, to me, clarifies that there are patients who don't meet the clinical trial enrollment criteria, but who still could potentially benefit from treatment?
Ultimately, what can this mean for ophthalmologists and the patients they treat?
It opens up the availability of another treatment option for patients who have thyroid eye disease. So for a long time, we didn't have much by way of medical treatment. We would use corticosteroids, there were off label uses of drugs like Rituximab or Tocilizumab.
But now that we have an FDA-approved drug for thyroid eye disease, it just makes it a little more supported by data. You know, we love seeing randomized placebo-controlled mass clinical trial data, as opposed to case reports and case series, which can be somewhat biased because we tend to report things that work.
We don't always report things that don't work. So having data where there was a significant difference between these 2 populations, I think is reassuring both to ophthalmologists, as well as to patients, that using TEPEZZA in thyroid eye disease of longer duration or low CAS score might still be effective.
And how can we help ensure that we have better outcomes for the patients?
In collecting data like this, the idea is to be objective, and as a trial investigator, we didn't again, know what treatment patients were receiving. So, having these data that really show that there seems to be some benefit for those patients who are treated with the drug can improve our outcomes for patients by then allowing us to present to them the possibility of using to pass that, in the whole scheme of things that we have to treat our patients with thyroid eye disease.
We have medical treatments, we have non-prescription medical treatments, we have surgical treatments that we use for these patients. and so it establishes TEPEZZA as one good option in that list of treatments that we have.
What kind of feedback are you getting from ophthalmologist?
So ophthalmologists want to see these kinds of data to help them to be confident in the decisions they're making to treat their patients. From ophthalmologists who are aware of these data, it helps them to say, Okay, if I have a patient with a longer duration of disease, or who has a low CAS, I can feel more confident in speaking to them about TEPEZZA as a potential treatment option because previously, maybe I wasn't so confident in the data that were coming out because they were not randomized, or the patients were being followed in a masked fashion.
So I think the ophthalmologists will be more confident in thinking about using TEPEZZA in their patients with thyroid disease of any duration, just as the FDA label has been changed to indicate.
And then what's the next step for the research or the trials? You know, where do we go from here?
There are still some unanswered questions, there are important things to pull out of these data, just under two thirds of patients who were treated with TEPEZZA had a response.
So it would be interesting to understand why 1/3 didn't respond, and in those numbers, the 2.5 millimeter reduction of proptosis. It is possible that the ones who responded actually had a better reduction of their proptosis and that that number is reduced by including all those patients who didn't respond as well. It might be that there's a predictor of response to and that would be really helpful to me as an ophthalmologist to be able to say, ‘Okay, you're coming to me with your more chronic, longer duration thyroid eye disease, I think you should get TEPEZZA rather than surgery because you fit into this particular category.’
So I think that's really important. And finally, I think, overall, with any drug, we want to know how durable is the response. Is this an effect that's going to last for 1, 2 or 5 years? There are some longer term data that have come out from those patients in the phase three trial who were followed for many months afterwards showing that in the majority of them, they do have a durable clinical benefit. We would like to see that that's the case in these more chronic patients who were evaluated as Well in this phase 4 study.