Last updated Feb. 24, 2022, by Marta Figueiredo, PhD
 Fact-checked by Joana Carvalho, PhD
Oxbryta (voxelotor) is a daily oral therapy developed by Global Blood Therapeutics (GBT) for sickle cell disease (SCD).
It was given accelerated approval by the U.S. Food and Drug Administration (FDA) in November 2019 to treat SCD patients, 12 and older, becoming the first therapy to target the disease’s underlying cause. The FDA extended Oxbryta’s approval in December 2021 to include children as young as 4.
Oxbryta, alone or in combination with standard hydroxyurea treatment, was also approved by the European Commission in February 2022 for SCD patients, 12 and older. The therapy is available as well in the United Arab Emirates for this patient population. Health authorities in the U.K. are deciding whether to approve it.
In December 2020, GBT launched an early access program for Oxbryta in Europe and other areas outside the U.S. to treat patients 12 and older who have no alternative treatment options and are unable to access the medication through clinical trials.
How does Oxbryta work?
Oxbryta is a small molecule that addresses the underlying cause of SCD, which is the clumping and sticking of faulty hemoglobin molecules into rigid, long rods that deform red blood cells into a sickle or crescent-like shape. Hemoglobin is the protein inside red blood cells that is responsible for oxygen transport.
This sickling destroys red blood cells (hemolysis), lowers hemoglobin levels, and blocks small blood vessels, triggering vaso-occlusive crises (VOCs) — when sickled red blood cells block blood flow to the point that tissues become deprived of oxygen.
The therapy works by binding to hemoglobin and increasing its affinity to oxygen, preventing its clumping and the subsequent sickling and destruction of red blood cells. As such, the therapy is expected to restore normal red blood cell function and oxygen delivery to tissues, reducing anemia, hemolysis, and VOCs.
Oxbryta in clinical trials
Oxbryta’s approval for patients 12 and older was supported by positive findings from a pivotal Phase 3 trial, called HOPE (NCT03036813). The global study assessed the safety and effectiveness of Oxbryta (900 mg or 1,500 mg tablets) against a placebo in 274 SCD patients, ages 12 to 65.
Top-line results from the first six months of treatment showed that 51% of the 90 patients receiving 1,500 mg of Oxbryta — the now-approved dose — achieved a hemoglobin response, defined as a hemoglobin increase of at least 1 gram per deciliter (g/dL), compared with 7% of those on a placebo.
The higher dose also significantly lowered the levels of bilirubin and reticulocytes — two biomarkers of hemolysis.
These benefits were seen regardless of concurrent use of hydroxyurea, a standard treatment to reduce VOC frequency and the need for blood transfusions.
HOPE’s longer-term data, comprising nearly 1.5 years of treatment, confirmed the six-month findings and revealed that Oxbryta also was superior to a placebo at lowering VOC frequency and easing, or fully healing, painful leg ulcers. The therapy was found to be generally safe and well-tolerated.
The GBT-sponsored Phase 2 HOPE-KIDS 1 study (NCT02850406) is evaluating Oxbryta’s safety, pharmacokinetics, and early effectiveness in up to 155 children, ages 9 months to 17 years, with SCD. The study is divided into four parts (A to D), each involving children of different ages assigned to receive single or multiple doses of the therapy, given at the 1,500 mg approved dose or a weight-based equivalent dose.
Recently presented interim data covered the first 45 children, ages 4–11, treated with Oxbryta for at least six months in group C (which includes children ages 12–17). The therapy was found to result in similar rises in hemoglobin levels and reductions in hemolysis to those observed in older patients who received the approved dose in HOPE.
These findings supported Oxbryta’s approval expansion to children as young as 4 in the U.S.
GBT also launched the international, placebo-controlled Phase 3 HOPE-KIDS 2 study (NCT04218084) to serve as a confirmatory trial for Oxbryta’s full approval in the U.S. The study may still be recruiting up to 224 children, ages 2–14, with SCD at sites across the U.S., Africa, and Europe.
Children with SCD are at a higher risk of stroke due to disease-associated increased blood flow in certain brain arteries. The main goal of HOPE-KIDS 2 is to assess whether Oxbryta is superior to a placebo at reducing this stroke risk — as assessed through a non-invasive ultrasound that detects changes in brain blood flow — after 24 weeks of treatment.
Secondary goals include other stroke risk evaluations and changes in the levels of hemoglobin and markers of hemolysis over time. The trial is expected to conclude in March 2026.
A multicenter Phase 4 study, called ActIVe (NCT04400487), is investigating Oxbryta’s effects on physical activity and sleep quality, as measured by a validated wrist-worn device, in up to 50 SCD patients, ages 12–55, living in the U.S. Enrollment is ongoing and the study is anticipated to end by February 2023.
Other details
Oxbryta, available in the form of 500 mg tablets and 300 mg dispersible tablets, is administered once daily with or without food at a recommended dose of 1,500 mg for patients 12 and older, and weight-based doses for children 4 to 12. Dispersible tablets are available only for the younger group.
Patients weighing 40 kg (about 88 lbs) or more should receive a 1,500 mg daily dose, while those weighing 20 (22 lbs) to 40 kg should be given 900 mg per day. Children weighing between 10 kg (22 lbs) and 20 kg should be treated with 600 mg once daily.
Lower doses are recommended for SCD patients with severe liver impairment. Details can be found on Oxbryta’s prescribing information label.
The therapy is contraindicated for patients with a history of allergic reactions to its active substance, voxelotor, or any of its ingredients.
Patients on Oxbryta can develop allergic reactions, such as generalized rash, hives, mild shortness of breath, mild facial swelling, and higher-than-normal levels of eosinophils, a type of white blood cell involved in such reactions. In the presence of any of these symptoms, Oxbryta should be stopped immediately and appropriate medical treatment administered.
The therapy’s most common side effects in patients 12 and older include headache, diarrhea, abdominal pain, nausea, rash, and fever. Vomiting was also noted in children younger than 12.
Given that there is no human data on Oxbryta’s use during pregnancy and breastfeeding, the therapy should be used during pregnancy only if its benefits outweigh potential risks. Breastfeeding is not recommended during Oxbryta treatment and for at least two weeks after the last dose.
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