Voxelotor for Sickle Cell Disease Wins FDA Nod for Patients as Young as 4

The oral polymerization inhibitor, a first-in-class therapy for sickle cell disease, was first approved by the FDA for adults and pediatric patients 12 years of age and older in 2019.

The FDA Friday approved the wider use of voxelotor (Oxbryta) in patients with sickle cell disease (SCD) as young as 4 years of age. In 2019, the oral polymerization inhibitor was approved by the FDA for adults and pediatric patients with SCD 12 years of age and older.

Voxelotor has a novel mechanism of action. The first-in-class therapy regulates the affinity of hemoglobin for oxygen, resulting in a decrease in the concentration of deoxygenated sickle hemoglobin (HbS), which forms polymers. It’s hypothesized that because oxygenated HbS cannot polymerize, modifying HbS to increase the proportion of oxygenated to deoxygenated HbS in red blood cells would alter disease severity.

In sickle cell disease, a lifelong, inherited blood disorder, red blood cells are abnormally shaped into a “sickle,” restricts the blood flow and limiting oxygen delivery to the body’s tissues, leading to severe pain and organ damage. It is also characterized by severe and chronic inflammation that worsens vaso-occlusive crises during which patients experience episodes of extreme pain and organ damage.

The FDA also approved a separate New Drug Application (sNDA) for voxelotor tablets for oral suspension, a 300-mg dispersible, once-daily tablet dosage form suitable for pediatric patients as well as for older patients who have difficulty swallowing entire tablets. The grape-flavored tablet dissolves in room-temperature clear drinks (such as water or clear soda).

In a statement, the Global Blood Therapeutics, the drug’s manufacturer, said voxelotor will now be available in 2 dosage forms for patients 4 years and older based on age, weight, and ability to swallow tablets: the 500-mg tablets and the dispersible tablets.

The FDA’s approval of the sNDA is based on data from the open-label phase 2a HOPE-KIDS 1 study, which showed that weight-based treatment with the dispersible tablet formulation resulted in rapid and sustained improvements in hemoglobin. Concurrent reduction of hemolysis was also shown.

In addition, the drug received a positive opinion from the Committee for Medicinal Products for Human Use of the European Medicines Agency, recommending marketing authorization for adults and pediatric patients 12 years and older.

Common adverse effects for patients were headache, diarrhea, abdominal pain, nausea, fatigue, rash, and pyrexia.