A diagnosis of sickle cell disease (SCD) portends a lifetime of seizures marked by significant pain, infections, anemia, and an increased risk of stroke. Sub-Saharan Africa is home to the majority of people living with sickle cell disease. Approximately 236,000 babies are born each year with sickle cell disease in sub-Saharan Africa (more than 80 times more than in the United States),1 and up to 90% will die in childhood, usually before their fifth birthday.1
In the United States, by contrast, people with SCD often live into their 40s or beyond. A significant contributor to this disparity is differential access to hydroxyurea, a chemotherapeutic agent that reduces the frequency of sickle cell crises and prolongs survival. The clinical benefit of hydroxyurea in people with SCD was first demonstrated more than two decades ago, and it was approved by the United States Food and Drug Administration (FDA) in 1998. So While hydroxyurea has become the standard of care for SCD in the United States, it has been grossly underutilized in sub-Saharan Africa. Concerns about the drug’s toxic effects and its effects on susceptibility to malaria initially prevented its widespread use. Recent studies have demonstrated that hydroxyurea is safe and effective in children in sub-Saharan Africa, with the treatment reducing vaso-occlusive crises, malaria incidence and mortality.2
Despite these benefits, efforts to introduce hydroxyurea throughout sub-Saharan Africa have been limited due to a shortage of rural clinicians, insufficient equipment for routine blood monitoring, and relatively high costs. The Novartis Africa Sickle Cell Program runs 11 treatment centers in Ghana that administer hydroxyurea and serve more than 2,000 patients, with plans to expand to Kenya, Uganda and Tanzania. Although admirable, this initiative represents only a small step towards access to hydroxyurea throughout the subcontinent. We believe a much greater effort is needed. A multi-country program with international support to support sickle cell therapies could prevent the deaths of hundreds of thousands of children. A framework for implementing such a program already exists: the President’s Emergency Plan for AIDS Relief (PEPFAR).
PEPFAR is the President’s emergency plan for the fight against AIDS. Information on PEPFAR operations comes from the US State Department.
PEPFAR is a US-led interagency effort that was launched in 2003 with strong bipartisan support; its objective is to fight the HIV pandemic by supplying and negotiating the prices of antiretroviral drugs and by setting up basic medical and social support services.3 The program has significantly increased resources for capacity building by funding African medical institutions to train additional health personnel and investing in infrastructure for laboratory testing across sub-Saharan Africa – including high-incidence regions sickle cell anemia (see map).3
Administration of hydroxyurea requires clinician supervision and periodic blood testing to support dose titration, efficacy, and safety. We believe there is potential to leverage the PEPFAR framework to expand the distribution, use, and monitoring of sickle cell drugs in resource-limited settings. These services could be piggybacked on existing PEPFAR initiatives. Employing PEPFAR-trained African health professionals could alleviate practical difficulties in rural areas; for example, existing PEPFAR staff and sites in these areas could perform routine clinical follow-up for people with sickle cell disease. These efforts could reduce bottlenecks in the delivery of SCD care. Although diagnostic capacity for sickle cell disease is limited in much of sub-Saharan Africa, improving access to treatment could spur national health systems to improve testing and foster enthusiasm for participation. community screening programs.
Prior to implementing a PEPFAR-based sickle cell treatment scale-up, a needs assessment should be conducted to identify potential barriers and facilitators. Using implementation science in the context of the PEPFAR framework to overcome barriers would be essential.
Leveraging the infrastructure used to conduct recent studies of sickle cell therapies could provide another avenue to support drug monitoring and disease surveillance. For example, the hydroxyurea trials and the phase 3 clinical trial of voxelotor, an anti-polymerization drug, involved research consortia or hospitals in Kenya, Uganda and Egypt. These studies established the basic infrastructure and plans for recruiting staff and for acquiring, using and maintaining the equipment needed to monitor drug efficacy and toxicity.2 The combination of resources would offset the costs, and such coordination might require only minor additions to efforts that have already included local community leaders and governments.
A PEPFAR-based program that subsidizes or negotiates the prices of sickle cell drugs would be another critical tool to expand access to treatment and foster sustainability. Using a recent analysis of a hydroxyurea formulation in sub-Saharan Africa,4 we have estimated that such a program would have an initial cost of less than $100 million per year (based on a figure of $67 per person treated). Funding for this program could be added to PEPFAR’s current $7 billion annual budget.3 A daily dose of hydroxyurea in Tanzania currently costs over US$1.4; for a drug requiring lifetime use, this amount can be prohibitive since the average household income is less than $30 per day. PEPFAR has negotiated dramatic price reductions for antiretrovirals. A similar effort to work with pharmaceutical companies to lower the price of generic hydroxyurea formulations to $0.10 per dose, for example, would result in substantial savings for the program and reduced financial barriers for patients. . Price negotiation approaches used for antiretroviral drugs could be applied to sickle cell therapies, and efforts to reduce prices could leverage PEPFAR’s existing supply chain and procurement systems. A PEPFAR-based program should also recognize the cooperation of pharmaceutical companies by emphasizing tools such as the Access to Medicines Index, which ranks companies on their efforts to make medicines affordable and accessible in 106 low- and middle-income countries. Raising attention to such practices could foster engagement, competition, economic growth and positive recognition, thereby encouraging companies to offer more lifesaving medicines at reasonable prices.
Other promising drugs for sickle cell disease are on the horizon, and the global health community can begin to develop a platform to support their implementation in regions that need them most. In addition to the voxelotor trial, a phase 3 trial was recently completed for I-glutamine, an antioxidant that prevents the adhesion of sickle cells to the microvasculature, and both drugs have been approved by the FDA for use in adults and some children. With an efficient distribution platform in place, new therapies could be rapidly introduced in sub-Saharan Africa.
Other international agencies and organizations could provide essential support for such a program, including the World Health Organization, the United Nations Children’s Fund, the Bill and Melinda Gates Foundation and the Global Fund to Fight AIDS, tuberculosis and malaria. The Global Fund, an international organization founded in 2002, has disbursed more than US$50 billion, including funds for insecticide-treated bed nets to prevent malaria transmission and medicines for millions of people with tuberculosis or of AIDS. Like PEPFAR, it has provided crucial infrastructure support to health systems in regions that have high rates of sickle cell disease, and its reach could expand to encompass sickle cell disease.
Support from PEPFAR, the Global Fund, other international health agencies and stakeholders, and regulators such as the FDA and the European Medicines Agency could accelerate testing, certification, and implementation of new therapies and minimize the need for redundant clinical trials in low-income countries. countries. The fundamental objective will be to generate evidence on the safety and effectiveness of these drugs for all children with sickle cell disease.5 Using resources put in place by PEPFAR and Global Fund-supported efforts to build a drug delivery pipeline would also be an important step towards creating sustainable programs – which could allow for further expansion and development of systems. health care, especially systems to treat other childhood illnesses.
Pharmaceutical companies are pushing gene therapies and biologics through research and development pipelines without a clear strategy to get these drugs to the populations that need them most. We believe the medical community should advocate for effective, safe and affordable therapies for sickle cell disease across sub-Saharan Africa. Leveraging existing platforms such as PEPFAR could help achieve this important goal.