John, you’re working with a very interesting new drug for immune thrombocytopenia. Tell me what the challenges were that you took on.

The main challenges were that what we’re looking at is immune thrombocytopenia in children who the disease has been going on for a long period of time and are having clinically significant bleeding. So we are only talking about a very small proportion of children so the difficulty was really getting a large enough cohort of children together to be able to run this study.

Now, for adults the problem is already sorted, is it?

For adults eltrombopag has already been tested and has been licensed and it is approved for adults who have either got on-going disease after splenectomy or are unable to go for splenectomy.

Now this is a thrombopoietin mimetic, what is it about it that it’s going to do, or you hypothesised it would do, for your children?

What we hope to see in the children is that the results would be similar to the adults, that it would boost the platelet count and, with that, it would reduce the amount of bleeding events that we see in children and improve their quality of life.

So what did you do in the study?

In the study it was rather complicated. The study was in two parts so the initial part was a randomisation between eltrombopag and placebo and that went on for 13 weeks. Then there was a subsequent 24 week period of open label eltrombopag, so everybody got the study drug. During that time we monitored platelet count, we assessed clinical response in reduction of bleeding problems.

It’s a bit difficult to do a control because the control would be things like splenectomy.

Actually the control was probably a lot of the children are often without any specific treatment at all. You are correct, the historical treatments have often been splenectomy but a lot of the families and a lot of the doctors alike, we worry about the rates of infection following splenectomy and life-threatening infections can occur. There’s also growing evidence about visceral blood clots and also there’s some malignancy following on from splenectomy so we’re trying to avoid those. The other standard of treatment would be long-term steroids but steroids affect the children’s behaviour, the bone growth, the bone strength and, again, they suppress the immune system and increase risks of infection. So this drug stimulates the platelets without that increased risk of infection and the adult data suggests it’s very safe so we wanted to confirm that in the children.

So it’s an unmet need; what happened in the study?

In the study we demonstrated that at least three-quarters of the children had a platelet response i.e. the platelet count came up to a level where we would see bleeding being prevented. That response was maintained, so we saw a durable response, in about 40-50% of the children and we saw the bleeding events come down from a baseline being about 75% subsequently later on to about 35% and by the end of the study bleeding events were down to about 25%.

And how statistically significant are those figures?

Compared to the placebo they were very highly significant because no responses or a very small number of responses were seen on placebo.

So this was a phase III study, potentially a pivotal trial, has it changed practice, then, do you think?

I think as the results filter through and applications towards licence go forward, it will change treatment. It gives children another option other than splenectomy. For some children it may not necessarily be the right thing to do but it gives another option there and I think it will significantly improve the quality of life for children.

What about the threshold of choice about which children to treat? Because there must be a difficult decision because not all of them need treatment.

Correct, many children, even those who have a low platelet count, won’t have bleeding events. If they’re having frequent bleeding events, they’re back and forth to the hospital or the worries about bleeding events are preventing the children doing sporting activities, then it may be the right decision. But for many children, yes, they may not need any treatment at all.

But that threshold for decision making, whether to treat or not, might have changed because you now have a more effective treatment?

The threshold for whether we should treat or not will always be there. If you want a drug like this it does need careful monitoring of the blood tests to make sure that they’re responding and also to make sure that there’s no problems developing with the drug. So it does require frequent monitoring. So some people, if they’re not having any bleeding events, they’re not bothered about running a more sedentary lifestyle, it may not be the right option for them. There is no magic formula for deciding who should have this, it is careful discussion with the child and with the family.

These are fairly dramatic figures; you’ve talked about halving the bleeding rate, so that’s a really hard endpoint, and you’re lifting the platelet count quite considerably, doubling that is it?

The platelet count at baseline was less than 30 for all the patients and in the study we just aimed to produce a safe platelet count of over 50. It doesn’t need to be a normal platelet count, it just needs to be a safe platelet count.

So what would you say to doctors with patients to treat right now as a result of this announcement you’ve made here at the EHA?

What I would say is think about the treatment options, certainly include this. Personally I would only be thinking about a splenectomy if a child had had opportunity to try this drug first.

What about the downside, though, of using eltrombopag? Is it difficult to use, are there toxicities?

It’s fairly easy to use; it’s either a tablet or a liquid preparation for younger children. There are some dietary restrictions around the time of it but most children who I looked after just took it at bedtime so they didn’t have to worry about that and it wasn’t an issue for most children. Side effect-wise the vast majority of children tolerated this very well. There were up to 5% of children having some abnormalities in the liver tests but they all improved on stopping the drug. There were no other significant side effects noted in the study so it does appear to be very safe.

It’s a fairly sophisticated modern medicine mimicking a bodily process, do you think other medicines like this will come along for ITP?

There are a few other companies who are producing drugs which are very similar to the eltrombopag and the work in adults would suggest that if you don’t respond to one you may respond to the other. They all have slightly different modes of action – some require injections and some don’t require the dietary restrictions so it’s just adding more choices.

And a brief message for doctors to take home would be what?

That we have another treatment to consider but always remember the vast majority of children actually don’t need any treatment. But in those who do, this is one to consider.

Is it the end of the road for splenectomy in this condition?

I’m not sure it will be, necessarily, the end of the road, there will always be some people who don’t respond to this or some people who this medicine just doesn’t suit them and they may prefer to go down the route of splenectomy.

John, thank you very much.

Thank you.