Voxelotor improves Hb levels, haemolysis markers in younger children with SCD

The use of voxelotor weight-based dosing equivalent to 1,500 mg appears to increase haemoglobin (Hb) levels and decrease clinical markers of haemolysis in patients aged 4–11 years with sickle cell disease (SCD), according to a study presented at EHA 2021.

This ongoing HOPE KIDS-1* part C study analysed 45 children aged 4–11 years with SCD (mean baseline Hb level of 8.6 g/dL and reticulocyte count of 10.4), of whom 95.6 percent had haemoglobin SS (HbSS) and 4.4 percent had HbSβ⁰ genotypes. All participants received weight-based dosing of voxelotor, in a form of dispersible tablets, equivalent to 1,500 mg for up to 48 weeks. [EHA 2021, abstract S260]

At 24 weeks, 47.1 percent of the participants achieved a >1.0 g/dL increase in Hb levels from baseline.

“[The] increases [were] detected as early as week 2, the first timepoint of the study,” said study author Dr Clark Brown from Children’s Healthcare of Atlanta, Georgia, US.

This finding was consistent with the results of the phase III HOPE trial wherein the majority of the patients achieved an increased Hb level, Brown noted.

Patients treated with voxelotor also demonstrated improvements in clinical measures of haemolysis, showing reductions from baseline in indirect bilirubin level (-38.6 percent), percentage of reticulocyte count (-3.3 percent), and lactate dehydrogenase level (-2.6 percent) at week 24.

Children treated with voxelotor in this current study also achieved exposures and percent Hb occupancy that were comparable to that of adolescents aged 12–17 years treated with the approved voxelotor 1,500 mg in the HOPE KIDS-1 part B study. “The pharmacokinetic models have successfully predicted equivalent paediatric and adolescent doses [of voxelotor],” Brown said.

About half of the participants experienced treatment-emergent adverse events (AEs), which were mostly grade 1 or 2. The most common AEs reported were diarrhoea, rash, and vomiting (11.1 percent each).

“Weight-based dose of voxelotor was well tolerated, … [with] no new safety signals identified in this paediatric cohort,” said Brown.

“Voxelotor … is [already] approved in the US for the treatment of SCD in adults and paediatric patients aged ≥12 years,” said Brown. “[In this study,] the efficacy of voxelotor [weight-based dosing] in patients with SCD aged 4–11 years was consistent with that observed in adults and adolescents (≥12 years) in the phase III HOPE trial,” Brown concluded.

“Together, these results support the use of voxelotor in paediatric patients with SCD aged 4 years and older as a potential strategy for early mitigation of the disease complications associated with SCD,” he added.

*HOPE KIDS-1: Hemoglobin oxygen affinity modulation to inhibit HbS polymerization study to evaluate the effect of GBT440 in pediatrics with sickle cell disease