In yet another sign of the FDA’s enhanced flexibility under commissioner Scott Gottlieb, Global Blood Therapeutics $GBT has managed to convinced the regulator to allow its experimental drug, voxelotor, to be evaluated under the accelerated approval pathway for sickle cell disease (SCD), a group of inherited red blood cell disorders that typically afflict those of African ancestry.
SCD impacts hemoglobin, a protein found in red blood cells that carries oxygen throughout the body, and is characterized by episodes of searing pain as well as organ damage.
On Monday, the San Francisco-based biotech said the FDA had agreed to let it apply for voxelotor’s approval under this fast-track pathway on the basis of its data from an ongoing late-stage study that showed the drug was raising hemoglobin levels, which the company deemed a reliable indicator that the once-daily oral therapy would likely reduce the risk of stroke.
Voxelotor is designed to work by increasing hemoglobin’s affinity for oxygen. SCD patients have atypical hemoglobin molecules, which can distort red blood cells into a sickle, or crescent, shape. Symptoms such as anemia, repeated infections and periodic episodes of pain, begin to appear in early childhood. These episodes deprive the body of oxygen-rich blood, which can culminate in widespread tissue and organ damage, particularly in the lungs, kidneys, spleen, heart and brain, and drastically diminish life expectancy.
Earlier this year, the company reported data from the first tranche of its phase III HOPE study, which showed voxelotor met the main goal of an improvement in hemoglobin greater than 1 g/dL with voxelotor 1500 mg, compared with placebo at 12 weeks. As part of ASH, the company provided updated 24-week results, which demonstrated the drug conferred a sustained improvement in hemoglobin levels.
Data showed that 65% of patients taking voxelotor 1500 mg (p<0.0001) achieved a greater than 1 g/dL increase in hemoglobin at 24 weeks versus 10% of patients on the placebo. Meanwhile, 33% of patients on the lower 900 mg voxelotor dose achieved (p=0.0159) a similar increase in hemoglobin levels.
In addition, voxelotor therapy was associated with fewer vaso-occlusive crises (VOCs) – painful complications of SCD which occur when sickle shaped red blood cells get stuck inside blood vessels – despite substantial increases in hemoglobin.
The drug was well tolerated with similar safety profiles between the two doses, and there was was no evidence of impairment of tissue oxygenation at either dose, the company said.
“These data from the Phase 3 HOPE Study, including the clinically meaningful and statistically significant increase in hemoglobin, have been a key element in the discussions with the FDA which led to the agency’s agreement with GBT’s proposal for voxelotor under the subpart H accelerated approval pathway,” GBT chief Ted Love said in a statement.
The company plans to request a pre-NDA meeting for the first quarter of next year, it said on Monday. If approved, it will conduct a separate study post-approval to show the drug can definitively reduce the risk of stroke.
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