ASH Annual Meeting and Exposition
ASH Annual Meeting and Exposition
December 09, 2017
3 min read

Voxelotor improves hemoglobin levels, hemolysis markers in sickle cell disease

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ATLANTA — Treatment with voxelotor appeared associated with considerable improvement in hemoglobin and reduced clinical measures of hemolysis among adolescents with sickle cell disease, according to preliminary phase 2a study results presented at the ASH Annual Meeting and Exposition.

Voxelotor (Global Blood Therapeutics) — a novel hemoglobin S polymerization inhibitor administered orally once daily — also appeared well tolerated.

“These interim results support ongoing clinical evaluation of this drug as a potential disease-modifying therapy for adults and children with sickle cell disease,” Carolyn C. Hoppe, MD, pediatric hematologist/oncologist and director of the hemoglobinopathy laboratory at UCSF Benioff Children’s Hospital Oakland, said during a press conference.

Sickle cell disease is characterized by abnormal hemoglobin in red blood cells. Patients experience progressive pain that affects nearly every organ system, and the condition is associated with early mortality.

Bone marrow transplant and gene therapy can be curative but are not available for the majority of patients, so new effective therapies are needed to treat the disease and prevent its complications.

Voxelotor — previously known as GBT440 — targets the primary cause, Hoppe said.

“What’s triggering the disease is the sickle cell mutation, which causes polymerization in the red cell,” she said. “If we can interrupt that early on, we can hopefully disrupt or interrupt the biologic pathways that lead to the complications of the disease.”

The open-label GBT440-007 study enrolled 24 children and adolescents aged 12 to 18 years with sickle cell disease. All participants received 900 mg voxelotor daily for 24 weeks.

Efficacy of voxelotor in pediatric patients as measured by improvement in anemia served as the primary study objective.

Secondary outcomes included the effect of the agent on clinical measures of hemolysis, changes in total symptom score as determined by a novel patient-reported outcome measurement, safety and tolerability.

The safety population included all 24 patients enrolled (median age, 14 years; range, 12-17; 58% male). The efficacy population included 12 patients (median age, 13 years; range, 12-17; 50% male) who underwent treatment for at least 16 weeks.

The majority (88%) of patients enrolled were on stable dosing of daily hydroxyurea, the standard of care, and most either had zero (46%) or one (46%) vaso-occlusive crisis in the previous year.

“These patients were pretty typical of what we see in the clinic,” Hoppe said. “This was an unselected population for symptom severity.”

The efficacy analysis revealed what Hoppe called “a remarkable increase in hemoglobin level.”


Fifty-five percent of patients achieved a hemoglobin response of more than 1 g/dL at 16 weeks. Those responders were the study participants who demonstrated the greatest adherence and achieved the greatest exposure to voxelotor.

Ten of 12 patients demonstrated reduction in total symptom score from baseline to week 16. Five of 12 (41.6%) participants had a mean total symptom score of 0 by that time point.

Voxelotor also appeared well tolerated. One case of grade 3 rash occurred; all other adverse events were grade 1 or grade 2. Three patients (12.5%) experienced nausea, two (8.3%) experienced headache (8.3%) and two (8.3%) developed rash.

Researchers reported no serious drug-related adverse events, and no patients discontinued the study due to adverse events. The agent’s safety profile appeared similar to what has been observed among adults treated with the drug, Hoppe said.

Enrollment is underway for a second cohort in which a higher dose level — 1,500 mg daily for 24 weeks — will be studied.

Enrollment also is underway for the pivotal double-blind, placebo-controlled, randomized phase 3 HOPE trial, which will evaluate voxelotor in up to 400 adults and adolescents with sickle cell disease who have had at least one episode of vaso-occlusive crisis in the prior year.

“The improvement in symptom scores in very mildly symptomatic patients ... supports [this agent’s] use in a phase 3 trial,” Hoppe said. – by Mark Leiser


For more information:

Hoppe CC, et al. Abstract 689. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.


Disclosures: Hoppe reports research funding from, board of directors membership with and an advisory role with Global Blood Therapeutics. Please see the abstract for all other authors’ relevant financial disclosures.