A diagnosis of sickle cell disease (SCD) predicts a life of crises characterized by significant pain, infections, anemia and an increased risk of stroke. Sub-Saharan Africa is home to the majority of people with SCZ. Each year, approximately 236,000 babies with SCD are born in sub-Saharan Africa (more than 80 times as many as in the United States),1 and up to 90% die during childhood, usually before their fifth birthday.1
In contrast, in the United States, people with SCD often live in their 40s or older. A major cause of 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 US Food and Drug Administration (FDA) in 1998. While hydroxyurea has become the standard treatment for SCD in the United States, it has been vastly underutilized in Sub-Saharan Africa. Concerns about the drug’s toxic effects and its effects on malaria vulnerability initially prevented its widespread use. Recent studies have shown that hydroxyurea is safe and effective in children in sub-Saharan Africa, with treatment reducing vaso-occlusive crises, malaria incidence and mortality.2
Despite these benefits, efforts to introduce hydroxyurea in sub-Saharan Africa have been limited due to a lack of rural clinicians, insufficient equipment for routine blood monitoring, and relatively high costs. The Novartis Africa Sickle Cell Disease Program operates 11 treatment centers in Ghana that administer hydroxyurea and serves more than 2,000 patients, with plans to expand to Kenya, Uganda and Tanzania. While admirable, this initiative is only a small step towards access to hydroxyurea across the subcontinent. We believe that a much greater effort is required. A multi-country program with international support to support therapies for SCD could prevent the death of hundreds of thousands of children. One structure already exists for implementing such a program: the US President’s Emergency Plan to Fight AIDS (PEPFAR).
PEPFAR stands for the US President’s emergency plan to fight AIDS. Information on PEPFAR operations comes from the United States Department of State.
PEPFAR is a US-led multi-agency effort launched in 2003 with strong bipartisan support; the aim is to fight the HIV pandemic by supplying and negotiating prices of antiretroviral drugs and establishing basic medical and social support services.3 The program dramatically expanded capacity building resources by funding African medical institutions to train additional health personnel and investing in laboratory testing infrastructure across sub-Saharan Africa – including regions with a high incidence of SCD (see Map).3
Administration of Hydroxyurea requires physician supervision and periodic blood tests to support dose titration, efficacy and safety. We believe it would be feasible to leverage the PEPFAR framework to expand the distribution, use, and monitoring of drugs for SCD in resource-constrained environments. These services can be grafted onto existing PEPFAR initiatives. Hiring PEPFAR-trained African health workers could alleviate the practical difficulties in rural areas; For example, existing PEPFAR staff and sites in these regions could perform routine clinical follow-up for people with SCD. Through these efforts, bottlenecks in care for SCZ can be removed. While the capacity to diagnose SCD is limited in much of sub-Saharan Africa, better access to treatments could spur national health care systems to improve testing and spark enthusiasm for participation in community-based screening programs.
Before implementing a PEPFAR-based extension of SCD treatment, a needs assessment should be performed to identify potential barriers and facilitating factors. It would be critical to use implementation science in the context of the PEPFAR framework to address barriers.
Leveraging the infrastructure used to conduct recent studies of therapies for SCD could provide another opportunity to support drug and disease surveillance. For example, hydroxyurea studies and the phase 3 clinical trial of voxelotor, an antipolymerization drug, involved research consortia or hospitals in Kenya, Uganda and Egypt. These studies established the basic infrastructure and blueprints for recruiting personnel and for acquiring, using and maintaining the equipment needed to monitor the efficacy and toxicity of drugs.2 Combining resources would offset the costs, and such coordination may require only minor additions to efforts that have already involved local community leaders and governments.
A PEPFAR-based program that subsidizes or negotiates drug prices for SCZ would be another critical tool to expand access to treatment and promote sustainability. Using a recent analysis of a hydroxyurea formulation in sub-Saharan Africa,4 we estimate that such a program would have an initial cost of less than $100 million per year (based on a cost 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$14; for a drug to be used for a lifetime, this amount can be prohibitive, given that the median household income is less than $30 a day. PEPFAR caused drastic price reductions for antiretrovirals. A similar effort to work with drug companies to lower the price of generic hydroxyurea formulations to $0.10 per dose, for example, would translate into substantial savings for the program and reduced financial barriers for patients. Price negotiation approaches used for antiretroviral drugs can be applied to therapies for SCD, and efforts to lower prices can benefit from PEPFAR’s existing supply chain management and procurement systems. A PEPFAR-based program should also recognize collaboration between pharmaceutical companies by emphasizing instruments such as the Access to Medicine Index, which ranks companies based on their efforts to make medicines affordable and accessible in 106 low- and middle-income countries. Bringing attention to such practices can promote engagement, competition, economic growth and positive recognition, encouraging companies to make more life-saving medicines available at reasonable prices.
More promising drugs for SCD are on the horizon and the global health community can begin to develop a platform to support their implementation in regions of greatest need. In addition to the voxelor study, a Phase 3 study was recently completed for: Iglutamine, an antioxidant that prevents sickle cell attachment to the microvasculature, and both drugs are FDA-approved for use in adults and some children. With an effective delivery platform, new therapies can be rapidly introduced in sub-Saharan Africa.
Other international bodies and organizations could support such a vital 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 $50 billion, including funds for insecticide-treated bed nets to prevent the transmission of malaria and medicines for millions of people with tuberculosis or AIDS. Like PEPFAR, it has provided critical infrastructure support to health systems in regions with high SCD rates, and its scope could grow to include SCD.
Support from PEPFAR, the Global Fund, other international health agencies and stakeholders, and regulatory agencies such as the FDA and the European Medicines Agency could accelerate the testing, certification and implementation of new therapies and minimize the need for redundant clinical trials in low-income countries. The fundamental goal will be to generate evidence on the safety and efficacy of such drugs for all children with SCD.5 Using resources set up by PEPFAR and Global Fund-supported efforts to build a drug delivery pipeline would also be an important step toward creating sustainable programs — one that expands and expands further. development of health care systems, in particular systems to address other childhood diseases.
Pharmaceutical companies are pushing gene therapies and biologics through research and development pipelines without a clear strategy for introducing these drugs to the population in greatest need. We believe the medical community should advocate for effective, safe and affordable therapies for SCD in sub-Saharan Africa. By leveraging existing platforms such as PEPFAR, this important goal can be achieved.