Disease Focus : Bridging the Gap in Sickle Cell Disease Management across Africa

In a world increasingly focused on combating cancer, sickle cell disease (SCD) has emerged as a significant risk factor for haematological malignancies. SCD and its variants, such as Sickle Cell Anemia (SS) and Sickle Beta-Zero Thalassemia, are characterized by a transformation in the shape of red blood cells. Instead of their normal, smooth, doughnut-like structure, these red blood cells take on a crescent or half-moon shape.

 Because of this abnormal shape, these sickle cells become rigid and sticky, which can impede blood flow. This impairment hinders the body’s ability to produce sufficient haemoglobin, the protein responsible for transporting oxygen. The absence of adequate haemoglobin can lead to organ oxygen deprivation. Individuals with SCD often experience a range of debilitating symptoms, from mild to severe pain, swelling of the hands and feet, recurrent infections, delayed growth, vision impairments, and, in severe cases, acute chest syndrome.

Despite the availability of low-cost preventative therapies, inadequate resource allocation has hindered progress made in reducing the burden of SCD as compared to other public health initiatives in Africa. This article will highlight the prevalence, management options, and recent breakthroughs in SCD treatment in Africa, which are all essential for enhancing the quality of life for affected individuals.

A CONTINENT IN CRISIS

With sickle cell disease (SCD) being considered more prevalent in Africa, the World Health Organization (WHO) estimates that as of 2022, approximately 66% of the 120 million global cases originated in Africa. Nigeria has the highest disease burden in Africa and the globe, with over 150,000 births per year. The Federal Ministry of Health in Nigeria further estimates that about 50-90% of these individuals die before the age of five, with approximately 24% of Nigerians possessing the sickle cell trait.

Apart from Nigeria, other nations, such as Kenya, also bear this burden, with roughly 14,000 infants born with sickle cell disease annually. The Kenyan Ministry of Health data further indicates that this disease burden is consistent with malaria endemic patterns, with high prevalence in the lake region, western and coastal regions, and widespread prevalence in urban and commercialized areas due to migratory trends.

In 2019, the WHO reported that 38,403 people in Africa died from sickle cell disease, a 26% increase from 2000. This increased burden was caused by insufficient investment in disease-fighting activities, leaving many regional public health facilities needing help to provide the necessary preventive, early detection, and care services. Additionally, a lack of competent professionals and inadequate services at lower-level health facilities limit an effective response to the disease.

 In recognition of this crisis, Dr Matshidiso Moeti, WHO Regional Director for Africa, has been keen on calling for better resource allocation. “Most African countries do not have the necessary resources to provide comprehensive care for people with sickle cell disease despite the availability of proven cost-effective interventions for prevention, early diagnosis, and management of this condition,” she said.

A MULTI-PRONGED APPROACH

Given that there is no definitive treatment for SCD, standard medications have been used to help minimize disease-related adverse effects. These drugs include hydroxyurea, which reduces the frequency of sickle cell crises; voxelotor (Oxbryta), which diminishes sickling while increasing the number of red blood cells; crizanlizumab (Adakveo), which makes red blood cells more slippery and reduces pain crises; and L-glutamine, which is taken orally to relieve pain.

Although bone marrow transplant is currently the only known cure for SCD, it is considered complex and risky and only available to select people. Scientists have also developed novel methods, such as gene therapy, which is regarded as a potential cure for sickle cell anaemia. Gene therapy involves replacing a defective gene with a healthy one, which allows the body to create normal red blood cells.

According to Nicole Verdun, M.D., director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research, “Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited.”

As of December 2023, the FDA authorized Casgevy and Lyfgenia as emerging gene therapies, a significant step forward in SCD treatment as a potential alternative therapy for patients aged 12 and above. Casgevy uses CRISPR gene-editing technology, a revolutionary technique that allows for precise gene editing to increase foetal haemoglobin production, improve oxygen supply, and prevent sickling. In contrast, Lyfgenia inserts a gene into the patient’s blood stem cells, resulting in normal haemoglobin.

THE EVOLVING LANDSCAPE OF SICKLE CELL DISEASE TREATMENTS

As hydroxyurea and other drugs become more widely available worldwide, a significant unmet need for innovative treatments for sickle cell disease (SCD) remains. Sickle cell anaemia, which has long been categorized as an orphan disease, has prompted both the U.S. FDA and the European Medicines Agency (EMA) to incentivize pharmaceutical companies.

These incentives include shorter approval periods and lower development costs for innovative therapies, encouraging greater investment in SCD treatments. Major pharmaceutical corporations have often been promised extended exclusivity periods, free from generic competition.

With SCD becoming increasingly prevalent in regions like Africa, there is a growing opportunity to attract investments in these emerging markets. One major beneficiary of these incentives is Novartis. The company has now developed child-friendly formulations of hydroxyurea to facilitate easier medicine administration for children who struggle to swallow capsules. Additionally, Novartis is conducting two clinical trials in Ghana and Kenya for its next-generation SCD medication. If approved, these trials would represent the first use of biological therapy, rather than a vaccine, in multicenter clinical studies in Sub-Saharan Africa, excluding South Africa.

Pfizer, a Novartis competitor, also holds a substantial market share. In August 2022, Pfizer spent US$5.4 billion on Global Blood Therapeutics, the creator of Oxybryta, to extend its SCD portfolio. This acquisition expanded Pfizer’s rare haematology portfolio by introducing two new pipeline assets, GBT601 and inclacumab, both of which target SCD. Similarly, in September 2022, Danish pharmaceutical titan Novo Nordisk paid US$1.1 billion for Forma Therapeutics to extend its blood disorder medicine portfolio.

Unlike traditional SCD therapies, novel gene treatments are gaining traction in the SCD treatment landscape. Casgevy, developed collaboratively by Vertex Pharmaceuticals and CRISPR Therapeutics, and Lyfgenia by Bluebird Bio, are emerging as promising alternatives to bone marrow transplants. Dr Cece Calhoun, MD, MBA, a haematologist-oncologist at Yale Medicine, notes that these therapies represent a significant advancement. Additionally, Editas Medicine has entered this competitive arena with EDIT-301, an experimental gene editing treatment for SCD that could rival Casgevy.

HARNESSING AFRICA’S BOTANICAL POWER

Conventional medications, such as hydroxyurea, have long been the primary treatment for sickle cell disease (SCD). However, traditional African treatments present considerably more advanced health and wellness concepts than many biomedical scientists might expect. In regions like Nigeria, doctors have been using Fagara (Fagara zanthoxyloides) to alleviate the agonizing symptoms of sickle cell anaemia. This plant possesses unique properties that inhibit the stickiness of platelets and blood cells, offering an alternative approach to managing the disease.

Nigeria has also developed Niprisan, a remarkable drug formulated by the Nigerian National Institute for Pharmaceutical Research and Development (NIPRD). This phytochemical blend is derived from four indigenous plants: Piper guineenses seeds, Pterocarpus osun stems, Eugenia caryophylum fruit, and Sorghum bicolor leaves. While Niprisan is not a cure for sickle cell anaemia, it has proven effective in significantly reducing the frequency of painful crises in patients without causing toxicity or severe adverse effects.

STRENGTHENING AFRICA’S FIGHT AGAINST SCD

With Africa disproportionately affected by Sickle Cell Disease (SCD), the use of technologies such as newborn screening (NBS) remains underutilized. However, Africa could benefit from lessons learned in developed nations, where healthcare systems have successfully integrated NBS programs into antenatal care. This early detection approach not only improves data collection and analysis but also enhances accurate monitoring of disease impacts and outcomes. Furthermore, it promotes scientific research, training, and collaboration, all of which are crucial in shaping a comprehensive SCD treatment plan.

 In June 2024, WHO Africa took another significant step by issuing major recommendations to intensify Africa’s fight against SCD. These recommendations, captured in the ‘Guidance Framework for Sickle Cell Disease Management’ and the ‘Harmonised Guide for Sickle Cell Disease Management,’ offer precise, actionable solutions. They aim to help countries improve the quality of care, expand access to treatments, and enhance overall health outcomes in the fight against SCD across the region.

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