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Challenges and new horizons for sickle cell disease

2018; Elsevier BV; Volume: 5; Issue: 2 Linguagem: Inglês

10.1016/s2352-3026(18)30005-x

2451-9960

The Lancet Haematology,

Metabolism and Genetic Disorders

Last year, the US Food and Drug Administration (FDA) approved the use of L-glutamine for the treatment of patients aged 5 years and older with sickle cell disease, on the basis of the results of a randomised phase 3 clinical trial. This trial demonstrated that patients treated with L-glutamine for 48 weeks had reduced frequency and length of hospital visits for sickle cell pain crisis compared with patients treated with placebo. As increased oxidant stress is a major contributor to the pathophysiology of sickle cell disease, increasing the amount of circulating glutamine helps red blood cells produce more of the antioxidant nicotinamide adenine dinucleotide, allowing sickle-shaped red blood cells to regain flexibility. Although L-glutamine is not a new drug or therapy, it is the first new treatment for sickle cell disease to secure FDA approval in almost 20 years. This causes access issues for patients in a different way. In the USA, some insurance companies may be reluctant to cover an old drug, and in many other countries it is not licensed for use. However, on Jan 8, the company that produces the licensed version of L-glutamine announced that an Early Access Program would help physicians and patients in the European Union, Turkey, the Middle-East, and South America access the drug prior to authorisation. It should be noted that the European Medicines Agency granted orphan drug status to L-glutamine in 2012. Ultimately, it will be interesting to see whether generic L-glutamine can be as efficacious as the drug that has already been tested. Although it is heartening that there is now another treatment for patients with sickle cell disease beyond hydroxyurea and blood transfusions, social challenges persist. Blood transfusions remain a common method of treatment for patients with sickle cell disease, but the majority of blood donors in countries like the USA and the UK are white, whereas the majority of those with sickle cell disease are black. In the UK, 40 000 more black donors of all blood groups are needed to meet the growing demand for better matched blood and to supply rare blood types common to that ethnicity, in particular the Ro subtype. Currently, only 1% of people who give blood in England are black. The UK National Health Service Blood and Transplant has been working to encourage donors from ethnic minorities via campaigns such as Represent Campaign, which partners with the Music of Black Origin (MOBO) organisation to highlight the need for black and Asian donors. Last year, the B Positive choir, which brings together people who live with sickle cell disease through music, made their television debut at the 2017 MOBO awards. There are also obviously issues surrounding ethnicity and provision of care. Racism has been highlighted as a barrier to provision of care in the USA, and there are issues with inadequate training for those in emergency departments who are generalists who know little about sickle cell disease and their patients' need for pain relief. These issues are compounded by the opioid addiction crisis sweeping the USA, which has made doctors wary of prescribing pain relief medication. Although there are obviously many challenges for patients with sickle cell disease, there are several promising therapies in development. Several early-phase clinical studies were presented at the recent American Society of Hematology (ASH) annual meeting that showed encouraging activity, from gene therapy to immunotherapy. The phase 1/2 HGB-206 study used the LentiGlobin BB305 lentiviral vector for the production of β-A-Thr87Gln globin protein, which allows cells to overcome shortage in globin synthesis and prevent cells from sickling. The phase 2 SUSTAIN study tested the anti-P-selectin antibody crizanlizumab to block the vaso-occlusive process with the aim of delaying the time to first sickle cell pain crisis in adults. Voxelotor, a haemoglobin S allosteric modulator, has just been granted breakthrough therapy designation by the FDA. Voxelotor works by increasing haemoglobin's affinity for oxygen, preventing the polymerisation of haemoglobin that results in the sickling of red blood cells. Further encouraging news is that 2018 sees Alexis Thompson, MD, a world-renowned expert in sickle cell disease and thalassaemia, serve as president of ASH for a year-long term. Sickle cell disease remains a challenging disease to manage and to treat. It is imperative that resources are allocated to allow further research and supportive care for patients with the disease. While steps are being taken in the right direction, now is the time to turn around the rising mortality and provide adequate care for all individuals with sickle cell disease. For more information on sickle cell disease see The Lancet Clinic http://www.thelancet.com/clinical/diseases/sickle-cell-disease For more information on sickle cell disease see The Lancet Clinic http://www.thelancet.com/clinical/diseases/sickle-cell-disease