Can PEPFAR expand access to sickle cell disease treatment in Africa?

Of the 300,000 children born with sickle cell disease, or SCD, each year 236,000 live in sub-Saharan Africa. It is estimated that between 50-90% of these children will die before they turn five, usually from infection or severe anemia, making the disease “an invisible killer of children” in the region.

As many as 45% of people in sub-Saharan Africa are carriers of the sickle cell trait, making it the most prevalent genetic disease in the region. However, comprehensive care and newborn screening for the debilitating disease are not widely available, despite the existence of effective treatment.

The drug hydroxyurea —which is considered the standard of care for SCD in high-income countries —  decreases the frequency of pain episodes and prolongs survival for those suffering from the disease. While it gained FDA approval for use in adults in 1998, it’s still not widely available in low- and middle-income countries. Researchers were initially concerned about its use in children, particularly in countries with high rates of malaria infections, but a 2019 study deemed it safe for use in children in SSA as well.

In the United States, comprehensive SCD care has managed to reduce childhood mortality by 70%. However, deaths in Africa for both children and adults increased by 26% between 2000 and 2019 as a result of low investment in efforts to combat the disease.

Researchers say leveraging a program like the U.S. President’s Emergency Plan for AIDS Relief could help increase access to the drug by leveraging current lab infrastructure and health care workers.

Barriers to treatment

In people with SDC, red blood cells are “sickle”-shaped and therefore don’t bend or move as easily, blocking blood flow to the rest of the body. This can lead to serious symptoms including extreme pain episodes, life-threatening infections, stroke, or anemia. For those living with the disease and the frequent pain, keeping up with school and work can become impossible and often leads to poor mental health.

But many public health facilities in Africa lack the services for prevention, early detection, and care for sickle cell disease. A lack of health personnel with knowledge of the disease and its treatment, as well as a lack of services at lower-level health facilities, also hamper an effective response, according to WHO Africa.

While some pharmaceutical companies such as Novartis are implementing programs to help expand access to SCD diagnosis and treatment, “a much larger effort is required”, writes Dr. Mark A. Travassos, a pediatric infectious diseases specialist and associate professor of pediatrics at the University of Maryland School of Medicine in a recently published article in The New England Journal of Medicine.  

“A multicountry program with international backing to support therapies for SCD could prevent hundreds of thousands of children from dying. One structure for implementing such a program already exists: the U.S. President’s Emergency Plan for AIDS Relief,” Travassos and his co-author, Dr. Albert E. Zhou, who was affiliated with the University of Maryland School of Medicine at the time, wrote.

PEPFAR has been instrumental in expanding the capacity of the region’s healthcare workforce and laboratory testing infrastructure since its launch in 2003. It’s also uniquely positioned to negotiate the prices of medications such as hydroxyurea to make them accessible to patients in low-income settings, Zhou said.

Buying medications in larger volumes will generally result in lower prices. In the past, PEPFAR brokered a major cost reduction for antiretrovirals — which at the time were quite unaffordable — by improving supply chain and procurement systems, Zhou explained. Adapting land and sea-based transport instead of air cargo, for example, helped lower transportation costs by up to 85%.

Leslie Emegbuonye, the country director for Clinton Health Access Initiative in Ghana, said hydroxyurea treatment in the country is often limited to private sector providers and urban settings. SCD clinics in the country are also few and inequitably distributed, meaning patients must travel long distances to receive specialist care or seek care in private clinics, she said.

The drug was introduced in Ghana in 2018 but was only included in the National Health Insurance Scheme for treatment in children this year. The pediatric formulation of the drug, Hydroxyurea FCT, was recently launched in the country by Novartis, but isn’t included in the scheme, meaning caregivers who are able to find it end up paying for it out-of-pocket, Emegbuonye wrote in an email.

Ultimately, the prices of the drugs, including hydroxyurea, trickle down to the patient. In Ghana, “Poor financing mechanisms and subsidies to make the medication affordable amongst target populations” and “the absence of centralized or coordinated procurement and supply chain systems for improved access” leaves it largely inaccessible to patients, he said.

Leveraging PEPFAR infrastructure

HIV patients in sub-Saharan Africa faced similar access issues with antiretrovirals two decades ago, but initiatives such as PEPFAR and The Global Fund to Fight AIDS, Tuberculosis and Malaria found ways to finance and build out monitoring and treatment programs for HIV/AIDS in the region, explained Zhou.

A major barrier to the expansion of SCD treatment in the region is the limited healthcare personnel and the lack of capacity to monitor and treat patients in rural settings, he said. But PEPFAR has already invested in the education and training of healthcare providers in the treatment of HIV/AIDS.

“So our proposal is to extend the current capacity,” he said. “If we provide these nurses with further training for sickle cell disease management and treatment, this will not only empower the community but can also serve as another mechanism to roll out hydroxyurea.”

Using a 2020 analysis of a hydroxyurea formulation in sub-Saharan Africa, Travassos and Zhou estimate that a PEPFAR-based program would have an initial cost of less than $100 million per year, which equates to around $67 per person treated.

“This seems like a relatively small figure that can have a really massive impact across the continent,” Zhou said.

Patients on the medication need to have their blood count closely monitored to track side effects and adherence. One of the benefits of PEPFAR programs is that that kind of setup, as well as trained clinicians, already exist to monitor HIV patients' response to antiretrovirals, explained Travassos.

“So it doesn't seem like a huge leap to extend to use some of those devices and the same personnel to do that, to begin with, hydroxyurea,” he said.

A 2021 report on the integration of noncommunicable disease prevention and care into global health initiatives found examples of PEPFAR and Global Fund initiatives that were successfully expanded to NCDs. For example, in Zambia, an HIV/AIDS program found that women entering the clinics were at a higher risk of cervical lesions, so they began an expansion into cervical cancer screening.

“Over time, the development of the infrastructure and human resources through this funding [from PEPFAR] allowed the programme to offer these services to all women in the catchment area, regardless of their HIV status, with low marginal costs,” it said.

A multistakeholder approach

Addressing access to SCD treatment is ultimately a multistakeholder issue and larger efforts are needed, said James Hazel, research program manager at Access to Medicines Foundation. Increasing awareness and positive recognition through initiatives such as the Access to Medicine Index can really help incentivize pharmaceutical companies to price their medications competitively, according to Zhou.

In a country like Tanzania, where a daily dose of hydroxyurea costs more than $14 and the average household income is less than $30 per day, the medication — which requires lifelong use — is out of reach for most patients.

“Novartis and other companies have made great efforts to expand access, but unfortunately, it still only serves just a very small subset of the effective population,” he added.

Hazel believes that pharmaceutical companies are uniquely positioned to expand access in areas ranging from research and development of new products, all the way down to providing access to products already on the market.  

There could be redundancy or overlap of initiatives from multiple companies operating in the same low-income market, which is why it’s important that companies look to build capacity and strengthen health systems beyond simply their own products, Hazel explained. Instead, companies should look to invest in changes that are sustainable and beneficial to communities across the board, not just to one disease or one therapeutic.

We push companies to engage in collaborations — not only with governments and nonprofits — but with other pharmaceutical companies too, he said. “Pre-COVID there was more reluctance to engage in those cross-company partnerships. Now, I think we're starting to see an increased willingness to do so.”

Travassos said such collaborations need to move beyond clinicians and researchers, and move into the arena of the policymakers, political forces, governmental forces, and nongovernmental forces who can implement large-scale changes.

“There's an acute need and a desperation for it that they can immediately address,” he said.