Global Blood Therapeutics announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted Great Britain 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).
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Voxelotor, an oral treatment taken once daily, is the first medicine authorized in Great Britain that directly inhibits sickle hemoglobin (HbS) polymerization, the molecular basis of sickling and destruction of red blood cells in SCD.
SCD affects approximately 15,000 people in the UK. People living with SCD experience progressive, serious complications and morbidities, including organ damage, which lead to decreased quality of life and early mortality.
Furthermore, economic disadvantages and health inequalities experienced by many patients with SCD can have negative societal impacts in areas such as access to healthcare, education and employment.
In 2021, voxelotor was the first SCD treatment to receive a Promising Innovative Medicine (PIM) designation from the MHRA, which subsequently granted the medicine a positive scientific opinion under the Early Access to Medicines Scheme (EAMS).
This enabled healthcare professionals to treat selected patients with voxelotor prior to market authorization based on clinical factors to address a clear unmet medical need.
The marketing authorization by the MHRA, which follows the European Commission (EC) authorization earlier this year, is based on results demonstrating clinically meaningful and statistically significant improvements in hemoglobin (Hb) levels, accompanied by a reduction of hemolysis markers, for patients treated with voxelotor.
Data from the Phase 3 HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS Polymerization) Study of 274 patients 12 years of age and older with SCD showed that, after 24 weeks of treatment, 51.1% of patients receiving voxelotor achieved a greater than 1 g/dL increase in Hb compared with 6.5% receiving placebo (p<0.001), with significant improvements in markers of hemolysis in indirect bilirubin and reticulocyte percentage.
In the HOPE Study, the most common adverse reactions occurring in ≥10% of patients treated with Oxbryta with a difference of >3% compared to placebo were headache (26% vs. 22%), diarrhea (20% vs. 10%), abdominal pain (19% vs. 13%), nausea (17% vs. 10%), fatigue (14% vs. 10%), rash (14% vs. 10%) and pyrexia (12% vs. 7%).
Results from the HOPE Study were published in June 2019 in The New England Journal of Medicine and the analysis of the complete data from the HOPE Study was published in The Lancet Haematology in April 2021.
The EC decision, which was granted in February 2022, provides marketing authorization in all EU member states, as well as the additional member states of the European Economic Area, including Iceland, Liechtenstein and Norway. The MHRA grants marketing authorization in Great Britain.
It is estimated that more than 100,000 people in the United States, 52,000 people in Europe, up to 100,000 people in Brazil, and millions of people throughout the world have sickle cell disease (SCD).
SCD occurs particularly among those whose ancestors are from sub-Saharan Africa, though it also occurs in people of Hispanic, South Asian, Southern European and Middle Eastern ancestry. SCD is a lifelong inherited blood disorder that impacts hemoglobin, a protein carried by red blood cells that delivers oxygen to tissues and organs throughout the body.
Due to a genetic mutation, individuals with SCD form abnormal hemoglobin known as sickle hemoglobin. When sickle hemoglobin becomes deoxygenated, it polymerizes to form rods, which deforms the red blood cells into sickled – crescent-shaped, rigid – cells.
The recurrent sickling process causes destruction of the red blood cells, hemolysis and anemia (low hemoglobin due to red blood cell destruction), which drives vascular inflammation contributing to blockages in capillaries and small blood vessels (vaso-occlusion) that impede the flow of blood and oxygen delivery throughout the body.
Episodes of painful vascular occlusions are commonly referred to as vaso-occlusive crises (
OCs).
The diminished oxygen delivery to tissues and organs can lead to life-threatening complications, including stroke and irreversible organ damage.
Complications of SCD begin in early childhood and can include neurocognitive impairment, acute chest syndrome, and silent and overt stroke, among other serious issues. Early intervention and treatment of SCD have shown potential to modify the course of this disease, reduce symptoms and events, prevent long-term organ damage, and extend life expectancy. ■