Clinical Trial Updates (SCD)

Oxbryta (voxelotor)


Update: 31 March 2023

Preliminary draft guidance from England’s HTA body NICE states the product is not an acceptable use of National Health Service resources.

Previously the UK regulatory body MHRA grants marketing authorisation approval in

Oxbryta® (voxelotor) is intended for the treatment of haemolytic anaemia due to Sickle Cell Disease (SCD) in eligible adult and paediatric patients 12 years of age and older as monotherapy or in combination with hydroxycarbamide (hydroxyurea).

NICE will proceed to a public consultation on the preliminary recommendation, in advance of the final recommendation later in the year.



Update: 20 December 2022

Real-world data presented at the 64th American Society of Hematology Annual Meeting (ASH2022), held on December 10 –13 in New Orleans, showed:

  • A total of 4023 patients from the Symphony Health claims database were included in this analysis (mean [range] age: 34.5 [10 to 80] years; 59.8% female; mean [range] follow-up: 4.4 [0 to 26] months).
  • Compared with the 3-month pre-index period, significantly lower annualized rates of transfusions, VOCs, and hospitalizations, as well as lower annualized mean number of inpatient days, were observed. Specifically,
    o 50.6% (–61.4 to –41.0) decline rate for transfusions (n=248),
    o 23.1% (–29.9 to –19.3) decline rate for VOCs (n=1368),
    o 35.5% (–42.0 to –29.0) decline rate for VOC-related hospitalizations (n=757), and
    o 39.4% (–44.0 to –33.6) decline rate for all-cause hospitalizations (n=928).

Sources: Poster #807: Real-World Effectiveness of Voxelotor for the Treatment of Sickle Cell
Disease: Group and Pediatric Subgroup Analyses of Effects on Transfusions, VasoOcclusive Crises, and Hospitalizations


Update: 30 September 2022

Marketing authorization for Oxbryta® (voxelotor) has been granted by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA). The authorization enables the treatment of hemolytic anemia due to sickle cell disease (SCD) in adult and pediatric patients 12 years of age and older as monotherapy or in combination with hydroxycarbamide (hydroxyurea).

Voxelotor, an oral treatment taken once daily, is the first medicine authorized in the UK that directly inhibits sickle hemoglobin (HbS) polymerization, the molecular basis of sickling and destruction of red blood cells in SCD.



Update: 30 June 2022

Presented at EHA2022:

Data from the Retrospective Study to Evaluate Outcomes in Patients with Sickle Cell Disease Treated with Oxbryta (RETRO), the first multicenter, retrospective study to examine the real-world effectiveness of Oxbryta, demonstrated an improvement in anaemia and haemolysis as measured by an increase in Hb levels and decrease in markers of haemolysis – results consistent with the Phase 3 HOPE Study. A first-in-class, once-daily oral therapy, Oxbryta directly inhibits sickle haemoglobin polymerization, the root cause of the sickling and destruction of red blood cells in SCD. RETRO analyzed laboratory and clinical data from medical records of 216 patients treated at nine sites in the S., covering one year before and one year or more after initiation of Oxbryta treatment.

In the study, Hb levels increased and were maintained over the 12-month treatment period and peak Hb levels increased from baseline by a mean of 1.4 g/dL. Markers of haemolysis improved, with mean indirect bilirubin and mean reticulocyte percentage decreasing over the 12-month treatment period. Oxbryta was well tolerated, with the majority of treatment-emergent adverse events (TEAEs) being mild to moderate. Overall safety data was consistent with the Phase 3 HOPE Study of SCD patients ages 12 years and older.

In a separate retrospective analysis, researchers examined 12 years of data from the Clinical Practice Research Datalink and the Hospital Episode Statistics databases in the K., which provided sufficient data to observe end-organ damage events in patients with SCD. The analysis found that an increase in Hb of 1 g/dL was associated with a statistically significant (p<0.001) reduction in the risk for leg ulcers, pulmonary hypertension, chronic kidney disease, end-stage renal disease, acute chest syndrome and stroke.

Phase 1 data of GBT021601 (GBT601) support its progression into the Phase 2 portion of a Phase 2/3 trial:

    • Six adult patients with SCD (HbSS genotype) were studied in a single-arm, intra-patient single-dose and multiple ascending dose (MAD) trial to evaluate the safety and tolerability of GBT601, a next-generation HbS polymerization inhibitor.
    • In the MAD cohort at the end of treatment, a mean Hb occupancy of 32.6% was achieved, Hb increased by a mean of 2.3 g/dL, and there was an improvement in markers of haemolysis (reticulocytes, absolute reticulocytes, bilirubin and lactate dehydrogenase). In addition, improved red blood cell (RBC) health was reflected by ektacytometry results and peripheral blood smears. At the end of treatment, there was a mean decrease of 76.1% in the number of sickled RBCs (relative to pre-GBT601 dose measurements), and, following the 15-week washout period, the number returned near the pre-dose level. A similar trend was observed with Hb levels returning to near pre-dose levels following the washout period. There were no significant changes in the erythropoietin levels or other evidence of impaired oxygen delivery.
    • GBT601 demonstrated a favourable tolerability profile in both the SCD and the healthy volunteer portions of the trial. Overall, the majority of TEAEs were grade 1 or 2 and not related to GBT601. No TEAEs led to study discontinuation.
  • The Phase 2 portion of a planned, randomized, multicentre Phase 2/3 trial of GBT021601 (GBT601), to evaluate the safety, tolerability, and efficacy of GBT601 has been initiated.

About: GBT021601 (GBT601) has the same mechanism of action as Oxbryta (voxelotor), with the potential for improved clinical results by achieving higher haemoglobin levels and occupancy at a lower dose. GBT601 is being studied in a Phase 1 clinical trial and Phase 2 portion of a Phase 2/3 clinical trial.

  • The study will enroll up to 60 patients with SCD who are 18 to 65 years of age. Patients with haemoglobin (Hb) levels between 5.5 g/dL and 10.5 g/dL and 10 or fewer vaso-occlusive crises in the prior year are eligible for enrollment.
  • The study is planned to include sites in Africa, Europe, the Middle East, South America, and the United States, including several sites that are expected to begin enrolling patients in the near term.
  • The primary outcome measure is the number of participants with a change from baseline in Hb through Week 12. Secondary outcomes measures include assessments of PK and PD, as well as an assessment of the relationship between GBT601 and measures of anaemia and haemolysis.
  • Following the selection of the optimal safe and effective dose of GBT601 from the Phase 2 portion of the study, the Phase 3 portion will assess the efficacy and safety of the selected optimal dose compared to placebo in adult and pediatric SCD patients for 48 weeks. In addition, a third arm of the study will evaluate the PK and safety of single and multiple doses of GBT601 in an open-label single arm study with pediatric participants.



Update: 25 April 2022

  • The European Commission (EC) has granted Marketing Authorization for Oxbryta® (voxelotor) for the treatment of hemolytic anemia due to sickle cell disease (SCD) in adult and pediatric patients 12 years of age and older as monotherapy or in combination with hydroxycarbamide (hydroxyurea). Oxbryta, a once-daily, oral treatment, is the first medicine approved in Europe that directly inhibits sickle hemoglobin (HbS) polymerization, the molecular basis of sickling and destruction of red blood cells in SCD.
  • Available to eligible patients in the U.K. under an early access program. It received a positive scientific opinion by the U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA) under the Early Access to Medicines Scheme (EAMS).
  • A new formulation of Oxbryta (voxelotor) that is suitable for treating children as young as 4 is now available in the U.S. at specialty pharmacies. The U.S. Food and Drug Administration (FDA) expanded the approval of Oxbryta in late 2021 to treat children with sickle cell disease (SCD) as young as 4 — the therapy had previously been available as 500 milligram (mg) tablets and approved for use in patients ages 12 and older. At the time, the FDA also cleared a new oral suspension formulation of the therapy that is now available. The 300 mg oral
    suspension tablets, available in bottles of 60 or 90, include grape flavouring and are designed to be dispersed in room-temperature drinks like water or clear soda.



Update: 10 January 2022

  • The EMA has recommended granting a marketing authorisation in the EU for Oxbryta (voxelotor) for the treatment of haemolytic anaemia (excessive breakdown of red blood cells) due to sickle cell disease in patients 12 years of age and older. Oxbryta is to be used on its own or in combination with hydroxycarbamide (also known as hydroxyurea).
  • The main study that EMA’s recommendation is based on was a Phase 3, randomized, double-blind, placebo-controlled, multicentre study. The study investigated the safety and efficacy of voxelotor in 274 patients with sickle cell disease aged 12 to 65 years. Patients enrolled in the clinical trial had a baseline haemoglobin level between 5.5 and 10.5 g/dL. 90 patients received 1500 mg of voxelotor, 92 patients received 900 mg of voxelotor and 92 patients received a placebo. After 24 weeks of treatment, 51.1% of patients treated with 1,500 mg of voxelotor had a greater than 1 g/dl increase in their haemoglobin levels compared to 6.5% of those receiving placebo. These results were observed when Oxbryta was used on its own or in combination with hydroxyurea, which is the standard treatment for patients with sickle cell disease.
  • The most common side effects reported in clinical trials for Oxbryta included headache, diarrhea and abdominal pain.
  • The FDA has granted accelerated approval forOxbryta (voxelotor) to treat sickle cell disease in paediatric patients aged four up to 11 years. The FDA had previously granted accelerated approval for Oxbryta for patients aged 12 years and older with sickle cell disease.
  • Oxbryta is the first FDA-approved treatment for children with SCD that directly inhibits sickle hemoglobin polymerization, the root cause of the sickling and destruction of red blood cells in SCD.



Update: 27 October 2021

  • The U.S. Food and Drug Administration (FDA) has agreed to consider Global Blood Therapeutics’ (GBT) request to expand the use of Oxbryta (voxelotor) to children as young as 4 with sickle cell disease (SCD).
  • The oral therapy is currently conditionally approved — when given at a daily dose of 1,500 mg — to treat SCD patients ages 12 and older.
  • In a separate application, also now under FDA review, the company is asking for approval of a weight-based, dispersible tablet form of Oxbryta that is grape-flavored and can be mixed with water or other drinks at room temperature for easier swallowing. This new 300 mg formulation provides similar benefits to the tablet form available to older patients, GBT reported, and allows for weight-based dosing in younger children.
  • The FDA granted priority review to both applications, effectively shortening the process from 10 to six months. A final decision is expected on or before Dec. 25.



Update: 30 June 2021

A new analysis of data from 45 children with SCD, aged 4 to 11 years, enrolled in the open-label Phase 2a HOPE-KIDS 1 Study (GBT440-007) showed that treatment with Oxbryta (1,500 mg or weight-based equivalent dispersed in a pediatric-appropriate formulation) resulted in rapid and sustained improvements in hemoglobin.

An increase in hemoglobin of greater than 1 g/dL from baseline was observed in 47% of patients as early as two weeks and sustained through 24 weeks, consistent with results in patients ages 12 years and older in the Phase 3 HOPE Study. Concurrent improvements in markers of hemolysis were also observed. Relevant data was presented at EHA2021.



Update: 08 January 2021

No update available.


Update: 05 November 2020

72-week analysis of the Phase 3 HOPE Study of Oxbryta® (voxelotor) tablets will be presented at ASH2020 in December 2020.



Update: 25 August 2020

The European Medicines Agency (EMA) has granted Oxbryta® Priority Medicines (PRIME) designation, and the European Commission (EC) designated Oxbryta as an orphan medicinal product for the treatment of patients with SCD.

The company plans to submit a Marketing Authorization Application (MAA) to EMA to treat hemolytic anemia in sickle cell disease (SCD) patients ages 12 years and older by mid-2021.

The planned MAA will include data from the Phase 3 HOPE Study and the Phase 2 HOPE-KIDS 1 Study, both of which enrolled patients at clinical sites in Europe.

The company also intends to initiate an Early Access Program in Europe for patients and physicians who may need access to Oxbryta® prior to potential marketing authorization.

USA: Discussions for the potential use of Oxbryta® (voxelotor) for the treatment of sickle cell disease (SCD) in children ages 4 to 11 years are underway under the FDA’s accelerated approval pathway.


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