A diagnosis of sickle cell disease (SCD) heralds a lifetime of crises marked by substantial pain, infections, anemia, and an increased risk of stroke. Sub-Saharan Africa is home to the majority of people living with SCD. About 236,000 babies are born with SCD in sub-Saharan Africa each year (more than 80 times more than in the United States),1 and up to 90% will die in infancy, usually before their fifth birthday.1
In the United States, by contrast, people with SCD often live into their 40s or older. A major 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 was approved by the US Food and Drug Administration (FDA). It has been greatly underutilized in sub-Saharan Africa. Concerns about the drug’s toxic effects and effects on vulnerability to malaria initially prevented its widespread use. Recent studies have shown that hydroxyurea is safe and effective in children in sub-Saharan Africa, and that the treatment reduces vaso-occlusive crises, malaria incidence, and mortality.two
Despite these benefits, efforts to introduce hydroxyurea in sub-Saharan Africa have been limited due to a shortage of physicians in rural settings, insufficient equipment for routine blood screening, and relatively high costs. The Novartis Africa sickle cell disease program operates 11 treatment centers in Ghana that administer hydroxyurea, serving more than 2,000 patients, with plans to expand to Kenya, Uganda and Tanzania. Although admirable, this initiative represents only a small step in guaranteeing access to hydroxyurea throughout the subcontinent. We believe that a much greater effort is required. An internationally backed multinational program to support therapies for SCD could prevent the deaths of hundreds of thousands of children. A structure already exists to implement such a program: the US President’s Emergency Plan for AIDS Relief (PEPFAR).
PEPFAR denotes the United States President’s Emergency Plan for AIDS Relief. Information on PEPFAR operations is from the US Department of State.
PEPFAR is a US-led interagency effort that launched in 2003 with strong bipartisan support; its objective is to combat the HIV pandemic by supplying and negotiating the prices of antiretroviral drugs and establishing basic medical services and social support.3 The program dramatically expanded capacity-building resources by funding African medical institutions to train additional health care personnel and invest in infrastructure for laboratory testing throughout sub-Saharan Africa, including regions with a high incidence of SCD ( watch Map).3
Administration of hydroxyurea requires physician supervision and periodic blood tests to support dose titration, efficacy, and safety. We believe that it would be feasible to take advantage of the PEPFAR framework to expand the distribution, use, and monitoring of SCD medicines in resource-limited settings. These services could be incorporated into existing PEPFAR initiatives. Employing PEPFAR-trained African health professionals could alleviate practical challenges in rural areas; for example, existing PEPFAR staff and sites in these regions could perform routine clinical follow-up for people with SCD. These efforts could alleviate bottlenecks in the provision of SCD care. Although capacity to diagnose SCD is limited in much of sub-Saharan Africa, improving access to treatments could create incentives for national health care systems to improve testing and encourage enthusiasm for participation in screening programs community based.
Before implementing a PEPFAR-based SCD treatment expansion, a needs assessment should be conducted to identify potential barriers and facilitators. 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 SCD therapies could provide another avenue to support drug monitoring and disease surveillance. For example, trials of hydroxyurea 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 plans for recruiting personnel and for acquiring, using, and maintaining the equipment needed to monitor drug efficacy and toxicity.two The pooling of resources would offset the costs, and such coordination may require only minor additions to efforts that have already included local community leaders and governments.
A PEPFAR-based program that subsidizes or negotiates drug prices for SCD would be another critical tool to expand treatment access and foster 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 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 more than US$14; For a drug that requires lifetime use, this amount can be prohibitive, since the median household income is less than $30 a day. PEPFAR negotiated drastic price reductions for antiretrovirals. A similar effort to work with pharmaceutical companies to lower the price of generic formulations of hydroxyurea to $0.10 per dose, for example, would translate into substantial savings for the program and reduce financial barriers for patients. Price negotiation approaches used for antiretroviral drugs could be applied to SCD therapies, and efforts to reduce prices could take advantage of PEPFAR’s existing procurement and supply chain management systems. A PEPFAR-based program should also recognize the cooperation of pharmaceutical companies by emphasizing tools like the Access to Medicines Index, which ranks companies based on their efforts to make medicines affordable and accessible in 106 low- and middle-income countries. . Drawing attention to such practices could foster engagement, competition, economic growth and positive recognition, encouraging companies to offer more life-saving medicines at reasonable prices.
Additional promising medicines for SCD are on the horizon, and the global health community can begin to develop a platform to support their deployment in regions of greatest need. In addition to the voxelotor trial, a phase 3 trial for me-glutamine, an antioxidant that prevents the adherence of sickle cells to the microvasculature, and both drugs have been approved by the FDA for use in adults and some children. With an effective delivery platform, new therapies could be rapidly introduced in sub-Saharan Africa.
Other international agencies and organizations could provide critical 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, the Tuberculosis and Malaria. The Global Fund, an international organization founded in 2002, has disbursed more than $50 billion, including funding for insecticide-treated mosquito nets to prevent malaria transmission and medicines for millions of people with tuberculosis or AIDS. Like PEPFAR, it has provided critical infrastructure support to health systems in regions that have high rates of SCD, and its reach could grow to encompass 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 rollout of new therapies and minimize the need for clinical trials. redundant in low-income countries. countries. The fundamental objective will be to generate evidence on the safety and efficacy of these medications for all children with SCD.5 Using the resources established 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 could allow for further expansion and development of drug delivery systems. health care, particularly systems to address other childhood illnesses.
Pharmaceutical companies are guiding gene therapies and biologics through lines of research and development without a clear strategy for introducing these drugs to populations most in need. We believe that the medical community should advocate for effective, safe, and affordable therapies for SCD throughout sub-Saharan Africa. Leveraging existing platforms like PEPFAR could help achieve this important goal.