New therapeutics for children with sickle cell disease: A time for celebration, caution, or both?

Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study

“…Instead, ODC of hemoglobin containing voxelotormodified species has the opposite hyperbolic shape, showing less proportional oxygen off-loading, that is, less oxygen delivery, when tissues are more hypoxic (Figure 2A). The need to balance voxelotor's ability to prevent sickling by increasing oxygen affinity against voxelotor's negative effect on oxygen delivery was ardently articulated in a commentary by Quinn and Ware, 29 and the recent NEJM review by Bunn. 30 High-affinity Hgb F also shifts ODC to the left, but the sigmoidal shape is maintained, as is shown in our patients with high Hgb F prior to starting voxelotor (Figure 2A).…”

“…(A) Hemoglobin and (B) the percent predicted peak oxygen consumption (% predicted peak VO 2 ) of each subject at baseline and after voxelotor therapy. (C) Peak VO 2 ranges of male and female subjects before (yellow bar, CPET#1) and after (red bar, CPET#2) voxelotor therapy, compared to healthy adolescents29,30 (green bar), and Olympic runners31,32 (teal bar). p-Values are calculated by two-tailed paired t-tests.…”

Efficacy and safety of pharmacological interventions for managing sickle cell disease complications in children and adolescents: Systematic review with network meta‐analysis

“…Therapeutic options for this disease are still limited, especially for the pediatric population, and current clinical practice guidelines are not straightforward for selecting therapies for this population 10–12 . Although recent pipelines in the context of clinical trials demonstrated promising results with gene therapies toward the cure of SCD, bone marrow or stem cell transplantations are the only available curative approaches for these patients 13 . Other nonpharmacological treatments as chronic blood transfusions can also be used to reduce symptoms; yet, these procedures are associated with several barriers including patients’ eligibility, treatment access, costs, and related complications (e.g., abnormally high levels of iron in the blood, reactions due to a mismatch between donors and recipients) 14,15 …”

“…[10][11][12] Although recent pipelines in the context of clinical trials demonstrated promising results with gene therapies toward the cure of SCD, bone marrow or stem cell transplantations are the only available curative approaches for these patients. 13 Other nonpharmacological treatments as chronic blood transfusions can also be used to reduce symptoms; yet, these procedures are associated with several barriers including patients' eligibility, treatment access, costs, and related complications (e.g., abnormally high levels of iron in the blood, reactions due to a mismatch between donors and recipients). 14,15 According to Tambor et al, 15 some pharmacological interventions collectively termed as "disease-modifying therapies," intended to prevent or reduce the occurrence of SCD-related symptoms and complications and to improve long-term outcomes, are globally available.…”