Oxbryta Safe and Effective in Children Ages 4 to 11, Early Trial Data Indicates

Six months of treatment with Oxbryta (voxelotor) safely and effectively increased hemoglobin levels and reduced red blood cell destruction, or hemolysis, in children ages 4–11 with sickle cell disease (SCD), according to data from the ongoing Phase 2 HOPE-KIDS 1 trial.

These findings are consistent with those previously reported for adolescents and adults with SCD given Oxbryta in the Phase 3 HOPE study (NCT03036813), which supported the therapy’s conditional approval for patients, ages 12 and older, in the U.S.

Global Blood Therapeutics (GBT), the therapy’s developer, expects these positive and comparable results will help to support a planned request to expand Oxbryta’s label in the U.S. to children as young as 4 years old.

“New treatment options for younger children with sickle cell disease are urgently needed,” Ted W. Love, MD, GBT’s president and CEO, said in a press release.

“We believe that reducing the sickling and destruction of red blood cells, thereby improving the anemia and hemolysis that characterize this devastating inherited condition early in life, could modify the course of the disease and alleviate serious and life-threatening complications,” Love added.

An international, confirmatory Phase 3 trial, called HOPE-KIDS 2 (NCT04218084), is also underway in children ages 2 to 14. This trial, designed to support Oxbryta’s accelerated approval in the U.S., is enrolling at sites worldwide (information is here).

The therapy is also under regulatory review in Europe for SCD patients, 12 and older.

These and other data, such as real-world evidence supporting the use of Oxbryta in patients ages 12 and older, will be shared across six oral and poster presentations at the upcoming European Hematology Association (EHA) 2021 Virtual Congress, set for June 9–17.

SCD is characterized by the clumping and sticking of faulty hemoglobin molecules into rigid, long rods (polymers) that deform red blood cells into a sickle or crescent shape. Hemoglobin is the protein inside red blood cells that is responsible for oxygen transport.

Oxbryta, the first approved SCD therapy targeting its underlying cause, works by increasing hemoglobin’s affinity to oxygen, thereby preventing its polymerization, or clumping, and red blood cell sickling. The therapy is given as an oral tablet.

The ongoing, global, Phase 2 HOPE-KIDS 1 study (NCT02850406) is designed to evaluate Oxbryta’s safety, pharmacokinetics (movement into, through, and out of the body), and early effectiveness in up to 155 children with SCD.

The study comprises four parts, each involving patients of differing age ranges, from 9 months to 17 years, and assigned to single or multiple doses of the therapy. (It is still marked as enrolling, possibly in the youngest patient age only; site and contact information is here.)

In the oral presentation, “Safety and Efficacy of Voxelotor In Pediatric Patients With Sickle Cell Disease Aged 4-11 Years,” researchers will present data covering 45 children, ages 4–11, treated with Oxbryta at a dose of 1,500 mg or its weight-based equivalent, once daily for up to 48 weeks (nearly one year).

Children’s median age was 7 and slightly more than half (51.1%) were girls. Most (84.4%) were receiving hydroxyurea, and 53.3% had at least one vaso-oclusive crisis (VOC) in the year prior to enrollment. Of note, VOCs are acute episodes of pain caused by the clumping of sickled red blood cells in blood vessels.

Hydroxyurea, a standard treatment to lower VOC frequency and the need for blood transfusions, was allowed during the trial in those on a stable dose of the therapy for at least three months before entering HOPE-KIDS 1.

Results showed that after 24 weeks (nearly six months) of treatment, hemoglobin levels rose by a mean of 1 gram per deciliter (g/dL), and that 47.1% of children achieved a hemoglobin response, defined as a hemoglobin raise of at least 1 g/dL.

A reduction in the levels of bilirubin (by 38.6%), lactate dehydrogenase (by 2.6%), and reticulocytes (by 3.3%) — all markers of hemolysis — were also reported.

Similar benefits in hemoglobin levels and hemolysis markers were also observed among children using hydroxyurea at a maximum tolerated dose, supporting Oxbryta’s potential to improve the health of these children beyond standard treatment.

Oxbryta was well-tolerated, with the most commonly reported treatment-related adverse events being diarrhea (11%), vomiting (11%), and rash (11%). Oxbryta-related adverse events led to treatment discontinuation in 9% of patients. No new safety concerns were identified.

HOPE-KIDS 1 findings were consistent with the durable rises in hemoglobin levels and reductions in hemolysis markers reported in adults and adolescents on 1,500 mg of Oxbryta daily in the Phase 3 HOPE study.

“These results support the use of voxelotor in pediatric patients with SCD [4 years and older] as a potential strategy for early mitigation of the morbidity and mortality associated with SCD,” the researchers wrote.

Real-world data on Oxbryta’s use in patients ages 12 and older will also be presented at EHA in two posters.

In one, “Real-World Experience of Voxelotor For the Treatment of Patients with Sickle Cell Disease – A Single-Center Study,” researchers will share data from 73 SCD adult and adolescent patients given Oxbryta at a single center in South Carolina.

Results detailed in the poster’s abstract showed that after an average of 3.9 months of treatment (range, 0.5–13.6 months) patients’ hemoglobin levels had increased, while those of hemolysis markers had decreased.

Patients also reported having greater energy, a better activity tolerance, fewer pain symptoms, and reduced scleral icterus (yellowing of the white part of the eye).

Again, these improvements were observed despite most patients being on a stable dose of hydroxyurea, and were comparable to those reported in the HOPE trial, the researchers noted in the abstract.

The second poster, “Real-World Experience of Patients with Sickle Cell Disease Treated with Voxelotor: A Multicenter, Retrospective Study,” will provide comprehensive safety and efficacy data on Oxbryta’s use in about 300 patients treated for up to one year at nine U.S. clinical centers.

“We are encouraged by the extensive body of new data being presented at this year’s EHA Congress, supporting the use of Oxbryta in both real-world and clinical trial settings,” Love said.

“We look forward to potentially expanding access to Oxbryta over time across a broad range of sickle cell disease patients in the U.S., Europe, the Gulf Cooperation Council region and other areas,” he added.