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Potential Role of Syk Inhibitors in ITP

Panelists: Ivy Altomare, MD, Duke University Medical Center; Terry Gernsheimer, MD, Fred Hutchingson Cancer Research Center; Keith R McCrae, MD, The Cleveland Clinic
Published: Thursday, Mar 01, 2018



Transcript: 

Ivy Altomare, MD: What about new agents? What do we have coming down the road? I would imagine that new agents are probably most often being tested in the refractory setting? I’d like to start with fostamatinib.

Terry Gernsheimer, MD: That’s an interesting drug. It’s a Syk inhibitor.

Ivy Altomare, MD: What’s a Syk inhibitor?

Terry Gernsheimer, MD: I’m not an immunologist, so I don’t want to start getting into that. But, basically, we’re changing the immunology of recognizing these cells, or platelets, as targets.

Ivy Altomare, MD: OK. Syk standards for spleen tyrosine kinase, I believe?

Terry Gernsheimer, MD: Yes.

Ivy Altomare, MD: I haven’t heard of another Syk inhibitor available. Is that the first-in-class?

Terry Gernsheimer, MD: As far as I know, it’s the first-in-class. The original data, which looked at the usual endpoint (which is 50,000, at least doubling of the platelet count in patients who were at less than 30,000 to start), didn’t look great. It was about 18% on response rate. If we look at the data, if we look at a secondary analysis, what are we really looking for in patients? We’re really looking for clinical safety, right? We’re not necessarily looking for that 50,000 target because, frankly, other than the TPO mimetics, I’m not looking for that 50,000. I’m usually looking for greater than 20,000 or 30,000, because that’s usually what will keep patients safe. And, that’s what the guidelines say. If you look at the secondary analysis with fostamatinib, what you find is that they looked at, let’s say, 30,000, or at least a 20,000 increase. And when you look at that, we’re talking more like 40%, 45%. So, it’s promising. I think we need some more long-term data, which I think they’re in the process of obtaining.

Ivy Altomare, MD: Yes.

Terry Gernsheimer, MD: But, it is definitely somewhat promising. So, I’m excited about it.
Ivy Altomare, MD: A response rate of 40-ish percent in refractory...

Terry Gernsheimer, MD: That’s the clinically significant response rate, as opposed to the usual response rate that we’re looking for, which is greater than 50,000.

Ivy Altomare, MD: And this drug is oral?

Terry Gernsheimer, MD: It’s an oral drug.

Ivy Altomare, MD: OK. So, it’s oral, continuous?

Terry Gernsheimer, MD: Yes. You have to take it daily. You lose the response if you stop the drug.

Ivy Altomare, MD: What’s known about the tolerability?

Terry Gernsheimer, MD: Actually, it’s been relatively well tolerated. Initially, we thought that we were seeing a lot of gastrointestinal side effects at higher doses, but it seems to be much better tolerated now. I was looking at the data yesterday and I’m actually pretty impressed that it is a tolerable drug. It will have a place, along with a lot of other drugs that are coming down the pike that are looking at immunosuppression in other ways.

Transcript Edited for Clarity 

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Transcript: 

Ivy Altomare, MD: What about new agents? What do we have coming down the road? I would imagine that new agents are probably most often being tested in the refractory setting? I’d like to start with fostamatinib.

Terry Gernsheimer, MD: That’s an interesting drug. It’s a Syk inhibitor.

Ivy Altomare, MD: What’s a Syk inhibitor?

Terry Gernsheimer, MD: I’m not an immunologist, so I don’t want to start getting into that. But, basically, we’re changing the immunology of recognizing these cells, or platelets, as targets.

Ivy Altomare, MD: OK. Syk standards for spleen tyrosine kinase, I believe?

Terry Gernsheimer, MD: Yes.

Ivy Altomare, MD: I haven’t heard of another Syk inhibitor available. Is that the first-in-class?

Terry Gernsheimer, MD: As far as I know, it’s the first-in-class. The original data, which looked at the usual endpoint (which is 50,000, at least doubling of the platelet count in patients who were at less than 30,000 to start), didn’t look great. It was about 18% on response rate. If we look at the data, if we look at a secondary analysis, what are we really looking for in patients? We’re really looking for clinical safety, right? We’re not necessarily looking for that 50,000 target because, frankly, other than the TPO mimetics, I’m not looking for that 50,000. I’m usually looking for greater than 20,000 or 30,000, because that’s usually what will keep patients safe. And, that’s what the guidelines say. If you look at the secondary analysis with fostamatinib, what you find is that they looked at, let’s say, 30,000, or at least a 20,000 increase. And when you look at that, we’re talking more like 40%, 45%. So, it’s promising. I think we need some more long-term data, which I think they’re in the process of obtaining.

Ivy Altomare, MD: Yes.

Terry Gernsheimer, MD: But, it is definitely somewhat promising. So, I’m excited about it.
Ivy Altomare, MD: A response rate of 40-ish percent in refractory...

Terry Gernsheimer, MD: That’s the clinically significant response rate, as opposed to the usual response rate that we’re looking for, which is greater than 50,000.

Ivy Altomare, MD: And this drug is oral?

Terry Gernsheimer, MD: It’s an oral drug.

Ivy Altomare, MD: OK. So, it’s oral, continuous?

Terry Gernsheimer, MD: Yes. You have to take it daily. You lose the response if you stop the drug.

Ivy Altomare, MD: What’s known about the tolerability?

Terry Gernsheimer, MD: Actually, it’s been relatively well tolerated. Initially, we thought that we were seeing a lot of gastrointestinal side effects at higher doses, but it seems to be much better tolerated now. I was looking at the data yesterday and I’m actually pretty impressed that it is a tolerable drug. It will have a place, along with a lot of other drugs that are coming down the pike that are looking at immunosuppression in other ways.

Transcript Edited for Clarity 
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