Voxelotor: A Novel Treatment for Sickle Cell Disease.

OBJECTIVE: To review the pharmacological characteristics, clinical evidence, and place in therapy of voxelotor for the treatment of sickle cell disease (SCD).

DATA SOURCES: A comprehensive literature search of PubMed (1966 to April 2020) was conducted. Key search terms included GBT440 , sickle cell , and voxelotor . Other sources were derived from bibliographies of articles, product labeling, manufacturer's website, and news releases. ClinicalTrials.gov was searched for additional studies.

STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were reviewed and evaluated. Case reports/series and phase 1 through 3 clinical trials were included.

DATA SYNTHESIS: SCD is an inherited disorder associated with significant morbidity and early mortality. Three medications approved for SCD reduce SCD-associated complications but do not selectively ameliorate the underlying disease. Voxelotor is a novel agent that targets the pathophysiology of SCD. A phase 3 trial reported an increase in mean Hb level from baseline for voxelotor compared with placebo (1.1 vs -0.1 g/dL; P < 0.001). Voxelotor is generally well tolerated, with common adverse effects including headache, diarrhea, nausea, and arthralgia.

RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Voxelotor may be considered for patients with SCD who have continued anemia and hemolysis despite being on maximum tolerated dose of hydroxyurea or in those who are hydroxyurea intolerant. Voxelotor is costly; therefore, both cost and benefit should be weighed before prescribing.

CONCLUSION: Voxelotor appears to be safe and effective as monotherapy or in combination with hydroxyurea for patients with SCD who are 12 years of age and older.