As new therapies designed to cut off sickle cell disease pathology at the root advance through the clinic, the field is moving beyond endpoints centered on pain crises to readouts based on hemoglobin. A single, standardized hemoglobin endpoint seems unlikely, however, as different classes of disease-modifying candidates boost different versions of hemoglobin.
The first test will be Global Blood’s NDA for voxelotor, which hinges on boosting endogenous hemoglobin levels. But a negative result will have little read through to the next disease-modifying therapies in line, which rely on engineered or fetal forms of hemoglobin.
Following the 2017 approval of Endari L-glutamine from Emmaus Life Sciences Inc. (Pink:EMMA), the first new sickle cell disease (SCD) therapy in almost 20 years, FDA is now considering two candidates for approval, which it will evaluate based on different primary endpoints.
Approval of the anti-P selectin antibody crizanlizumab from Novartis AG (NYSE:NVS; SIX:NOVN) will depend on the same established metric behind Endari's approval: reduction of vaso-occlusive crises (VOCs), painful episodes caused by blocked blood flow. An FDA decision is expected in early 2020.
The mAb is one of at