Sickle Cell Disease is an inherited disorder caused by a change in the structure of a DNA sequence that makes part of the protein known as haemoglobin abnormal. Haemoglobin is a compound found within red blood cells (RBCs) that binds oxygen and transport it from the lungs to the rest of the body. RBCs with the abnormal sickle cell haemoglobin do not function normally. They are stiff and when they lose oxygen they form into a shape of a sickle and stick together blocking small blood vessels. This blockage causes pain and breakdown of these cells which results in blood not having enough healthy red blood cells. The only current cure for SCD is a medical treatment where one’s bone marrow is infused with healthy blood-forming cells so as to replace the abnormal sickle cells. It is very expensive and chances of one getting a suitable donor are not high. 

There is, therefore, a need for treatments that can help alleviate the complications associated with the disease such as low level of healthy red blood cells and injury to the brain due to low oxygen levels. This study will involve participants with SCD who participated in voxelotor clinical trials. They will be enrolled to continue receiving voxelotor or started on voxelotor if they were receiving the alternative substance that has no effect on the body for comparison. All participants will receive voxelotor once a day in the form of tablets for swallowing, tablets for dissolving in water or a powder added to liquids. Participants who are 12 years old and above take 3 tablets that are 500mg each while those below 12 years will have their dose calculated using their body weight. The study will be conducted in multiple countries and involve approximately 70 global sites, with approximately 600 participants enrolled. Voxelotor presents the potential of been a drug that can be used in the early treatment of patients with sickle cell disease due to its ability to improve the low level of red blood cells by preventing their abnormal breakdown. Identified risks include mild reactions to the medication such as diarrhoea, abdominal pain, nausea, rash, and drug hypersensitivity, which were managed by dose reduction and/or treatment of symptoms without needing to discontinue treatment. Participants will therefore benefit from participating in this study and will be monitored for safety and SCD-related complications. Participants will be in the study for a minimum of 96 weeks and/or until they have access to voxelotor from an alternative source (e.g., through commercialization or a managed access program). The study will end when the last participant’s last visit occurs.

Sickle cell disease (SCD) is a rare, devastating, and debilitating disease marked by the pathophysiologic features of hemolytic anemia, vaso-occlusion, and progressive end-organ damage, with a clinical course characterized by life-long disability and early death.As current treatment options are limited, there remains a significant unmet medical need for novel therapies and for the early treatment of pediatric patients with SCD to mitigate the consequences of the disease.

Voxelotor (formerly known as GBT440) is an orally administered small molecule that inhibits HbS polymerization by allosterically modifying hemoglobin-oxygen (Hb-O2) affinity. It is approved in the United States for the treatment of SCD in adults and pediatric patients 4 years of age and older. By inhibiting HbS polymerization, voxelotor has been shown to improve RBC deformability and reduce blood viscosity. Treatment with voxelotor has also led to significant reductions in sickle cell counts in the peripheral blood, which supports the potential for voxelotor to serve as a disease-modifying therapy for SCD.

The objective of this OLE is to assess the safety of, and SCD-related complications with, long-term treatment with voxelotor in participants who have completed treatment in a GBT-sponsored voxelotor clinical study, based on the following parameters: 1. Adverse events (AEs), clinical laboratory tests, physical examinations (PEs), and other clinical measures 2.Frequency of SCD-related complications

This multicenter, nonrandomized OLE will be conducted globally and will be available to eligible participants from GBT-sponsored voxelotor clinical studies. Participants must have completed participation in their originating clinical study and must meet the entry criteria for this study to be eligible for enrollment. The study will be conducted at up to approximately 70 global clinical sites, and up to approximately 600 participants will be enrolled. All participants will receive voxelotor QD, administered orally as tablets, dispersible tablets, or a powder for oral suspension dosage form (packaged as stick packs). Participants aged ≥ 12 years will receive a voxelotor dose of 1500 mg QD. Participants aged < 12 years will receive a voxelotor dose based on their body weight, to provide exposure corresponding to the adult dose of 1500 mg QD. Participants may receive the study drug as long as receive clinical benefit that outweighs risk as determined by the Investigator for a minimum of 96 weeks and/or until they have access to voxelotor from an alternative source (e.g., through commercialization or a managed access program) and will end when the last participant’s last visit occurs.

Statistical programming and analyses will be performed using established statistical methods. Study data will be reported using summary tables, figures, and select data listings. Continuous variables will be summarized using mean, standard deviation, median, minimum, and maximum. Categorical variables will be summarized by presenting the number (frequency) and percentage in each category. All statistical analyses conducted will be descriptive and no formal statistical tests are planned. As appropriate, study data may be summarized separately based on the antecedent study.