Update on Phase 2a Voxelotor Data in Adolescents with Sickle Cell Disease Released

Updated 24-week data from patients treated with a 900 mg dose of voxelotor in the ongoing HOPE-KIDS 1 study, a phase 2a open-label study in adolescents ages 6 to 17 years with sickle cell disease (SCD), were announced today at the 23rd Congress of the European Hematology Association (EHA) in Stockholm, Sweden.

“We continue to be encouraged by the results of the ongoing HOPE-KIDS 1 study, which are consistent with inhibition of HbS polymerization by voxelotor and support its ongoing clinical evaluation as a potential disease-modifying therapy for both adults and adolescents with SCD,” said Ted W. Love, MD, president and chief executive officer of GBT in a recent statement.

The open-label, single- and multiple-dose HOPE-KIDS 1 study is evaluating the safety, tolerability, pharmacokinetics, and exploratory treatment effect of voxelotor in a pediatric population (ages 6 to 17) with SCD.

The study was divided into Parts A and B, with Part A evaluating a single 600 mg dose of voxelotor and Part B assessing the safety of voxelotor at doses of 900 mg and 1500 mg per day administered to patients between the ages of 12 and 17.

The analysis presented at the meeting looked at 22 patients who had been administered voxelotor 900 mg/day for 24 weeks in the Part B cohort of the study.

At 24 weeks, SCD participants showed increases in hemoglobin levels and improved clinical measures of hemolysis as evaluated by changes from baseline in hemoglobin, percent of reticulocytes, and percent of unconjugated bilirubin. More specifically, a hemoglobin response >1 g/dL at 24 weeks was achieved by 43% of SCD patients (9 of 21) with a median hemoglobin change from baseline of 0.7 g/dL. Furthermore, at 24 weeks, daily symptoms were reduced and improved in 13 of 21 SCD patients as assessed by total symptom scores (TSS).

A numerical decrease in transcranial doppler (TCD) flow was also experienced by 55% of SCD patients (11 of 20) at 24 weeks. Among those identified as hemoglobin responders (>1 g/dL), 88% (7 out of 8) were reported to have experienced a numerical decrease in TCD at 24 weeks.

In terms of safety and tolerability, a favorable tolerability profile in adolescents coincided with results in adults. Drug-related adverse events related to voxelotor were grade 1 or 2 with the exception of 1 grade 3 urticaria that did not recur with continued dosing. Nausea (12%), vomiting (8%), headache (8%), and rash (8%) were among the most common drug-related adverse events (occurring in 2 or more patients) noted. No drug-related discontinuations due to adverse events were reported.

A separate poster summarizing the single-dose pharmacokinetics (PK) of voxelotor in children and the multiple-dose PK of voxelotor in adolescents was also presented at the meeting. For this analysis, data from approximately 6 children (ages 6 to 11) who have completed Part A of the HOPE-KIDS 1 study and 25 adolescents (ages 12 to 17) who have completed Part B were included.

According to the results, voxelotor PK exposures in children after a single oral 600 mg dose were higher than in adolescents or adults, indicating that lower doses (on a weight or surface area basis) should be evaluated for future clinical trials in children. Additionally, following multiple 900 mg doses, voxelotor PK exposures in adolescents were similar to those observed in adults, suggesting adolescents may receive similar doses to adults. However, the need for lower doses in children younger than age 12 was also confirmed by physiologically-based PK modeling.

“Results to date support our ongoing development of voxelotor in a broad range of patients, including in our Phase 3 HOPE Study, which is also evaluating voxelotor at doses of 900 mg and 1500 mg per day in adolescents and adults,” added Dr Love. “We continue to expect to announce top-line clinical data from Part A of the HOPE Study by the end of this quarter.”