ASH 2025 | Safety and efficacy of etavopivat in adolescents with SCD: the ongoing HIBISCUS Kids trial

This is one of the first trials in children and adolescents that looked at etavopivat in children and adolescents with sickle cell disease. The primary objective of this study was really to assess the efficacy, the safety, the pharmacokinetics, and also to look at the hemoglobin response, the VOC, the TCD, and the fatigue scores. 25 patients were enrolled in the first cohort, and now I’m talking about the first cohort, which is the older cohort, and we have three other cohorts. The first cohort was a dose of 400 milligrams of the drug per day, and all the parameters I talked about were looked at, and the outcome was that children at this age group, children, adolescents, really had a very good response in terms of hemoglobin response, which was seen very early, as two weeks after treatment, and which was sustained up to 24 weeks. The analysis was done up to 24 weeks on 15 patients out of the 25. 

In addition, the hemolytic markers really improved markedly. And as we know, this is a hemolytic disease. So if we improve the hemolytic markers, we’re going to improve hemoglobin. In addition to that, the fatigue score and the fatigue is really a major problem in patients with sickle cell disease, which is due to the vaso-occlusive crisis and to the recurrent hemolysis and or chronic hemolysis, the fatigue scores improved remarkably, be it at week 12 or at week 24. And the last thing that was looked at was really the transcranial Doppler. Even though it was not a primary endpoint, it was looked at, and even though there was a variable trend, but four patients out of the 15 had improvement in the transcranial Doppler, meaning the predisposition to having stroke is really minimal. Once they improve, then they’re less predisposed to developing stroke. 

So overall… and of course, the safety profile was very good. There were no major treatment-emergent adverse events. There were no major drug interruptions at all. And these TEAEs that we’re seeing were really mild and usual, like things we see in sickle cell disease, like vaso-occlusive crisis, malaria in areas where there’s malaria, some headache, upper respiratory infections. So overall, I would say this is the first ongoing pediatric study, which has shown that etavopivat, which is the pyruvate kinase activator, which is known to improve the red cell health because it decreases 2,3-DPG and increases ATP, it showed that this drug is safe. So far, it’s effective. And the dosing is comparable in children and adolescents, to be more accurate, like adults. So we can extrapolate the dosage that was used in the HIBISCUS mother trial and use it in the pediatric age group. Cohort one has been finalized. Cohort two has been finalized. And we are now moving to younger cohorts as young as six months of age. So we’re very happy. We’re very optimistic.

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