Voxelotor 500mg tablets

This systematic review aims to summarise the clinical outcomes of l-glutamine, crizanlizumab, and voxelotor in the treatment of sickle cell disease (SCD) based on clinical trials and real-world data and to identify any gaps in the observations. The review identified 97 studies reporting data until 31 May 2024. A pivotal phase III study of l-glutamine showed that patients treated with l-glutamine had a 25 % reduction in pain crises and 33 % fewer hospital days compared to placebo. l-glutamine was generally well tolerated with minimal side effects. Real-world studies of l-glutamine emphasize patient adherence and obstacles to medication accessibility and approval as key concerns. In the SUSTAIN study, a 5-mg/kg dose of crizanlizumab reduced the occurrence of vaso-occlusive crises (VOCs) and hospitalizations by 45 % and 41 %, respectively. Real-world studies of crizanlizumab showed a reduction in complicated VOC events. The high discontinuation rate and results of the STAND trial led to a significant decrease in the use of crizanlizumab. The HOPE trial demonstrated a 51 % improvement in hemoglobin response and a reduction in hemolytic markers in patients treated with voxelotor. While some real-world studies have reported a decrease in VOCs and hospitalizations, the results are inconsistent and not conclusive. Further studies are needed to assess the impact of these novel therapies on end-organ-specific complications of SCD.

Abstract licence: CC BY-NC-ND

Sickle cell disease (SCD) is an inherited blood disorder in which sickle hemoglobin (HbS) polymerizes, leading to red blood cell sickling and chronic hemolytic anemia, vaso-occlusive crises, and end-organ damage associated with early mortality. Despite standard of care, patients with SCD still experience complications and early mortality, highlighting remaining unmet treatment needs. Voxelotor is a first-in-class HbS polymerization inhibitor approved by the US Food and Drug Administration as a treatment for SCD and by the European Medicines Agency for hemolytic anemia due to SCD. In clinical studies, voxelotor has been shown to increase hemoglobin (Hb) and decrease hemolytic markers in patients with SCD. The objective of this study was to estimate the impact of voxelotor on the burden of SCD in France using a modeling approach, accounting for its anticipated adoption and diffusion over the next 5 years. We designed a sequential multi-cohort model to project and compare the cumulative incidence of SCD complications over a 20-year time horizon in a world with and without voxelotor. A distribution of patients was simulated across various levels of Hb response based on the phase 3 HOPE trial results, and relative risk reduction was adjusted using published meta-analysis results that projected risk reduction due to a 1 g/dL increase in Hb. In 6100 modeled patients with SCD treated with voxelotor, the model projected the number of deaths to decrease by 39.4%, with an increase of 1.8% in life-years gained. The model also projected life expectancy to increase by 15.8%, and incident cases of stroke, pulmonary hypertension, and chronic kidney disease to decrease by 19.8%, 24.5%, and 25.1%, respectively. The model suggests that improving Hb using a treatment such as voxelotor may have a positive public health impact by reducing the burden of SCD for patients and the healthcare system.

Abstract licence: CC BY 4.0