Efficacy and safety of recently approved drugs for sickle cell disease: a review of clinical trials

Ali, Muhammad Ashar; Ahmad, Asrar; Chaudry, Hafsa Tahir; Aiman, Wajeeha; Aamir, Sobia; Anwar, Muhammad Yasir; Khan, Anam

doi:10.1016/j.exphem.2020.08.008

Cited by 52 publications

(42 citation statements)

References 39 publications

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“…Moreover, the reduction in hemolysis was demonstrated to be independent of HU, and the increase in Hb levels was not associated with an increased number in VOCs. 42 Despite the increase in Hb levels and the reduction in hemolysis, the VOC reduction was non-significant. 41 For this reason, voxelotor may represent a therapeutic option in patients with hemolytic complications, such as severe anemia, more than in patients with frequent and severe VOCs.…”

Section: Pharmacological Therapiesmentioning

confidence: 94%

Innovative Treatments for Rare Anemias

et al. 2021

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Rare anemias (RA) are mostly hereditary disorders with low prevalence and a broad spectrum of clinical severity, affecting different stages of erythropoiesis or red blood cell components. RA often remains underdiagnosed or misdiagnosed, and treatment options have been limited to supportive care for many years. During the last decades, the elucidation of the molecular mechanisms underlying several RA paved the way for developing new treatments. Innovative treatments other than supportive care and allogeneic bone marrow transplantation are currently in clinical trials for β-thalassemias, sickle cell disease (SCD), and congenital hemolytic anemias. Recently, luspatercept, an activin receptor ligand trap targeting ineffective erythropoiesis, has been approved as the first pharmacological treatment for transfusion-dependent β-thalassemia. L-glutamine, voxelotor, and crizanlizumab are new drugs approved SCD, targeting different steps of the complex pathophysiological mechanism. Gene therapy represents an innovative and encouraging strategy currently under evaluation in several RA and recently approved for β-thalassemia. Moreover, the advent of gene-editing technologies represents an additional option, mainly focused on correcting the defective gene or editing the expression of genes that regulate fetal hemoglobin synthesis. In this review, we aim to update the status of innovative treatments and the ongoing trials and discuss RA treatments' future directions. Interestingly, several molecules that showed promising results for treating one of these disorders are now under evaluation in the others. In the near future, the management of RA will probably consist of polypharmacotherapy tailored to patients' characteristics.

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Section: Pharmacological Therapiesmentioning

confidence: 94%

Innovative Treatments for Rare Anemias

et al. 2021

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“…Hydroxyurea is an antimetabolite drug which is in use for over four decades [ 1 ]. It is one of the earliest drugs that showed promise in the management of haemoglobinopathies and is the first FDA approved drug for the treatment of sickle cell disease (SCD) [ 2 ]. Despite being in use for several years, many aspects of hydroxyurea are either unknown or understudied; specifically, its usefulness in β-thalassaemia major and haemoglobin E β-thalassaemia is unclear [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

A comprehensive review of hydroxyurea for β-haemoglobinopathies: the role revisited during COVID-19 pandemic

Yasara

Premawardhena

Mettananda

2021

Orphanet J Rare Dis

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Background Hydroxyurea is one of the earliest drugs that showed promise in the management of haemoglobinopathies that include β-thalassaemia and sickle cell disease. Despite this, many aspects of hydroxyurea are either unknown or understudied; specifically, its usefulness in β-thalassaemia major and haemoglobin E β-thalassaemia is unclear. However, during COVID-19 pandemic, it has become a valuable adjunct to transfusion therapy in patients with β-haemoglobinopathies. In this review, we aim to explore the available in vitro and in vivo mechanistic data and the clinical utility of hydroxyurea in β-haemoglobinopathies with a special emphasis on its usefulness during the COVID-19 pandemic. Main body Hydroxyurea is an S-phase-specific drug that reversibly inhibits ribonucleoside diphosphate reductase enzyme which catalyses an essential step in the DNA biosynthesis. In human erythroid cells, it induces the expression of γ-globin, a fetal globin gene that is suppressed after birth. Through several molecular pathways described in this review, hydroxyurea exerts many favourable effects on the haemoglobin content, red blood cell indices, ineffective erythropoiesis, and blood rheology in patients with β-haemoglobinopathies. Currently, it is recommended for sickle cell disease and non-transfusion dependent β-thalassaemia. A number of clinical trials are ongoing to evaluate its usefulness in transfusion dependent β-thalassaemia. During the COVID-19 pandemic, it was widely used as an adjunct to transfusion therapy due to limitations in the availability of blood and logistical disturbances. Thus, it has become clear that hydroxyurea could play a remarkable role in reducing transfusion requirements of patients with haemoglobinopathies, especially when donor blood is a limited resource. Conclusion Hydroxyurea is a well-tolerated oral drug which has been in use for many decades. Through its actions of reversible inhibition of ribonucleoside diphosphate reductase enzyme and fetal haemoglobin induction, it exerts many favourable effects on patients with β-haemoglobinopathies. It is currently approved for the treatment of sickle cell disease and non-transfusion dependent β-thalassaemia. Also, there are various observations to suggest that hydroxyurea is an important adjunct in the treatment of transfusion dependent β-thalassaemia which should be confirmed by randomised clinical trials.

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“…The goal of the conference was to build on the previous annual meetings' themes and address some of the areas that delegates suggested for further coverage such as the role of community staff in haemoglobinopathies and preconception counselling. In light of the emergence of new therapies on the horizon, comes complexities in decision-making, increasing cost, limitation in access and the need for new strategies to ensure a sustainability in provision [1,2]. Sickle cell disease (SCD) and Thalassaemia are the leading disorders of haemoglobin referred to as haemoglobinopathies.…”

Section: Introductionmentioning

confidence: 99%

Annual Academy of Sickle Cell and Thalassaemia (ASCAT) conference: a summary of the proceedings

et al. 2020

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The fourteenth annual ASCAT conference was held 21–23 October 2019. The theme of the conference was ‘Sickle Cell and Thalassaemia disorders new treatment horizon; while ensuring patient safety and delivering excellence in routine patient care.’ Over the three-day conference, topics on current and novel models of care, advances in bone marrow transplant and gene therapy, as well as the psychosocial aspects of mind, body and health related quality of life were discussed. In addition, blood transfusion, apheresis, iron chelation therapy and acute haemolytic complications were presented. Quality standards in the diagnosis and treatment of sickle cell and thalassaemia were reviewed. Experts from Europe, the United Kingdom, the Middle East, the United States and Africa reported up-to-date scientific data, guides to comprehensive care, and current research into developing cures and advancing current therapy were described. In addition, oral and poster presentations on novel research from all over the world were shown during the conference.

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Efficacy and safety of recently approved drugs for sickle cell disease: a review of clinical trials

Cited by 52 publications

References 39 publications

Innovative Treatments for Rare Anemias

Innovative Treatments for Rare Anemias

A comprehensive review of hydroxyurea for β-haemoglobinopathies: the role revisited during COVID-19 pandemic

Annual Academy of Sickle Cell and Thalassaemia (ASCAT) conference: a summary of the proceedings

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