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U.K. MHRA Grants Marketing Authorization for GBT’s Oxbryta for Treatment of Hemolytic Anemia in SCD

July 26, 2022

The Medicines and Healthcare products Regulatory Agency (MHRA) has granted Great Britain marketing authorization for Global Blood Therapeutics’ Oxbryta for the treatment of hemolytic anemia due to sickle cell disease.

The approval of Oxbrya is for adult and pediatric patients 12 years of age and older as monotherapy or in combination with hydroxycarbamide (hydroxyurea).

Sickle cell disease (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 (VOCs). 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. SCD affects approximately 15,000 people in the United Kingdom.

Oxbryta (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.

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 percent of patients receiving voxelotor achieved a greater than 1 g/dL increase in Hb compared with 6.5 percent receiving placebo, with significant improvements in markers of hemolysis in indirect bilirubin and reticulocyte percentage. 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.

In November 2019, the U.S. Food and Drug Administration granted accelerated approval for voxelotor tablets, under the brand name Oxbryta, for the treatment of SCD in adults and children 12 years of age and older, and in December 2021, the FDA expanded the approved use of Oxbryta for the treatment of SCD in patients 4 years of age and older in the United States. As a condition of accelerated approval for patients ages 4 and older in the United States, GBT is studying Oxbryta in the HOPE-KIDS 2 Study, a post-approval confirmatory study using transcranial Doppler (TCD) flow velocity to assess the ability of the therapy to decrease stroke risk in children 2 to 14 years of age.

Author: Rare Daily Staff

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