Voxelotor (Oxbryta): A Comprehensive Clinical and Regulatory Monograph on a Novel Sickle Cell Disease Therapy and Its Market Withdrawal

I. Executive Summary

Voxelotor, marketed under the brand name Oxbryta, represents a landmark case in modern therapeutic development for rare diseases. Developed by Global Blood Therapeutics and later acquired by Pfizer, it was introduced as a first-in-class, small-molecule hemoglobin S (HbS) polymerization inhibitor, offering a novel, targeted therapeutic strategy for Sickle Cell Disease (SCD).[1] By directly addressing the root molecular pathology of SCD—the polymerization of deoxygenated HbS—Voxelotor was positioned as a potential disease-modifying agent, distinct from existing supportive care and symptom-management treatments.[2]

The drug's development was expedited through multiple regulatory pathways, culminating in an Accelerated Approval from the U.S. Food and Drug Administration (FDA) in November 2019 for patients aged 12 and older, with a subsequent expansion to children as young as four in 2021.[5] Marketing authorization from the European Medicines Agency (EMA) followed in February 2022.[2] These approvals were granted on the basis of a surrogate endpoint: a statistically significant increase in hemoglobin (Hb) levels, as demonstrated in the pivotal Phase 3 HOPE clinical trial.[4] This endpoint was deemed "reasonably likely to predict a clinical benefit," a cornerstone of the accelerated approval framework designed to hasten the availability of promising drugs for serious conditions with unmet medical needs.