Björn Mellgård, MD, PhD, Vice President, Global Program Lead, Rare Genetics and Hematology, Takeda, discusses the steps taken for Adzynma to get FDA approved for patients with congenital thrombotic thrombocytopenic purpura (cTTP).
Transcription:
We had a total of 46 patients included in the study. It was a comparative study. We compared then the standard of care, which most often is plasma or plasma-based product. We compared that to Adzynma, in such a way that each patient had six months treatment with Adzynma and six months treatment with standard of care.
For each patient, we had a comparison for each patient with both these products, which has a lot of advantages, especially when you have a relatively limited study population. We had 36 or 38 patients in this comparative exercise, and we tried to measure then what is clinically most important for the patients. I think it’s fair to admit that when you do the first controlled trial in a disease, you can always look back and say, “Why did we do this? Why did we do that?” But at the time when the trial was set up, there was nothing similar to that was ever being done.
We said, “Okay, these patients can obviously have acute events.” So of course, we want to measure the incidence of acute events. That’s really important. But there are also, let’s say, other indicators of disease activity, or uncontrolled disease, if I can call it that. We also wanted to measure those things.
Almost like a hallmark of this disease, when you have an uncontrolled disease, your blood platelets are dropping. What happens is that the platelets get trapped in these blood clots, and that’s why you have a drop in the platelets. We measured how often the patient fulfills certain criteria for a drop in platelets. We also measured milder neurological symptoms like tiredness, headache, and symptoms related to central nervousness. We looked specifically at abdominal pain, which is quite commonly reported. We also looked at kidney function, which can be a marker of disease activity, and something that long term is a risk.
What we found when we compared our data, between Adzynma and standard of care, was that during this comparative period, we saw a big advantage for Adzynma in terms of drop in platelets. It seems that there is less disease activity using this measurement when you are under treatment with Adzynma as compared to plasma-based therapies. We talked about this with acute events, and we were not sure how much of this we would see, but in the end, there was only one acute event happening during this comparative period when patients were treated with standard of care. We have seen zero acute events with Adzynma, not only during the comparative period, but also in the long term.
So, it seems that Adzynma provides a very strong protection from acute events. But if you compare it with standard care, it’s zero versus one, and it’s hard to draw any firm conclusions.
We also looked at something we called subacute events, which is then a combination of laboratory signs and symptoms. Because we said, you can have these things, what we call isolated manifestations, patient report a headache, a drop in platelets, or abdominal pain, and we counted all of those. But we said, “If you have two or three of these combined together, it’s still not really an acute event.” That’s what we then had as a measure of subacute events. What we saw during this comparative period, there were four patients who had five such subacute events during treatment with standard of care, and there was zero with Adzynma.
When we take these things together, and look at the safety profile, I guess that’s what FDA did in the end. They were looking at this, what we call totality of evidence.
To learn more about rare hematologic disorders such as congenital thrombotic thrombocytopenic purpura, visit CheckRare: https://checkrare.com/diseases/hematologic-disorders/
Learn more about Adzynma prescription information: https://content.takeda.com/?contenttype=PI&product=ADZ&language=ENG&country=USA&documentnumber=1