WHO Targets Pediatric Hydroxyurea for Sickle Cell Disease

What the WHO target changes

WHO’s September 2026 guidance update identifies the lack of suitable pediatric hydroxyurea formulations as an access problem, not simply a matter of prescribing practice. Its target product profile is intended to describe the characteristics a product should have to meet the needs of children and adolescents with sickle cell disease, particularly in health systems where compounding capacity and specialist services are limited.

A target product profile is a planning instrument. By defining preferred and minimally acceptable product characteristics, it can give manufacturers, regulators, donors and procurement agencies a common destination. That can reduce the risk that developers produce technically viable medicines that are difficult to dose, store, distribute or afford in the settings with the greatest burden.

The profile does not approve a product, guarantee quality or replace national treatment guidelines. It also does not establish a new hydroxyurea dose. Licensed indications, dosing, laboratory monitoring and regulatory requirements remain country- and product-specific.

Why formulation has become a policy issue

Hydroxyurea is an established disease-modifying treatment for sickle cell disease. Yet presentations designed around adults can be poorly suited to younger children who cannot reliably swallow solid dosage forms or who need doses adjusted for body size. Manipulating capsules or tablets may introduce dosing variability, occupational exposure concerns and additional work for families, pharmacies and clinics.

Extemporaneous compounding can address some of those problems, but it depends on trained personnel, validated preparation procedures, appropriate containers and reliable stability information. Those capabilities are not uniformly available. A commercially manufactured pediatric formulation could make dosing more reproducible and reduce reliance on local preparation, provided the product is acceptable to children and remains stable under realistic transport and storage conditions.

These requirements have direct procurement implications. A low unit price is not enough if the formulation requires unavailable equipment, frequent replacement, cold-chain capacity or packaging that leads to waste. Purchasers need to consider the complete cost of delivery, including freight, storage, dispensing tools, caregiver instructions and losses after opening.

The evidence supporting treatment access

The formulation priority rests on clinical evidence that hydroxyurea benefits children with sickle cell anemia, rather than evidence that one new pediatric presentation is already superior to another.

In the double-blind BABY HUG trial, 193 infants aged 9 to 18 months were randomized to hydroxyurea at 20 mg/kg per day or placebo for two years. The treatment did not significantly improve the trial’s coprimary measures of splenic and renal function. It did, however, reduce several prespecified clinical events: investigators recorded 177 pain events with hydroxyurea versus 375 with placebo, and 24 dactylitis events versus 123, with reported p-values of 0.002 and less than 0.0001, respectively.

Evidence from sub-Saharan Africa also supports the feasibility of delivering hydroxyurea in settings with a high disease burden. REACH was an open-label, phase 1/2 study involving 635 children aged 1 to 10 years in Angola, the Democratic Republic of Congo, Kenya and Uganda. After dose escalation, reported rates per 100 patient-years fell from 98.3 to 44.6 for vaso-occlusive pain, from 46.9 to 22.9 for malaria and from 3.6 to 1.1 for death.

REACH did not include a concurrent untreated control group. Its before-and-after comparisons therefore cannot establish that hydroxyurea alone caused every observed reduction. Together with randomized evidence, however, the findings support WHO’s premise that pediatric access is clinically important and feasible when treatment is paired with follow-up and laboratory capacity.

Turning a product profile into purchasing power

The clearest near-term use is tender design. National programs and pooled purchasers can translate the target profile into specifications covering dosage-form suitability, dose flexibility, shelf life, storage conditions, packaging, administration devices and quality documentation. Consistent specifications can also make demand more predictable for manufacturers considering investment in a pediatric product.

Procurement should preserve competition where possible. Specifications that are unnecessarily tied to a single concentration, package size or delivery device could narrow the supplier base without improving clinical use. Conversely, tenders based only on the lowest acquisition price may favor products that shift costs and complexity to clinics or caregivers.

The target profile may also guide product development. Manufacturers can use it to assess whether a liquid, dispersible tablet or another age-appropriate presentation is likely to meet program needs. Developers still must demonstrate pharmaceutical quality, stability, dose uniformity and, where required, bioequivalence or other clinical evidence acceptable to relevant regulators.

For US clinicians and policymakers, the profile is not an FDA standard and does not alter approved labeling. Its relevance lies in the framework it provides for evaluating pediatric usability and for supporting international procurement, humanitarian programs and global supply strategies.

Equity depends on the delivery system

A better formulation will not resolve the wider treatment gap by itself. Children must first receive an accurate diagnosis and remain connected to care. Programs also need trained prescribers, dependable blood-count testing, systems to respond to toxicity or treatment interruption, and financing that protects families from unaffordable recurring costs.

Geographic equity matters as well. Central procurement may lower prices, but medicines must still reach rural facilities without repeated stockouts. Packaging and instructions should support safe administration across languages and literacy levels. Pharmacovigilance systems need a practical route for clinicians and families to report suspected adverse effects and product-quality problems.

Demand forecasting is another vulnerability. Orders based only on the number of children currently receiving hydroxyurea will underestimate need where diagnosis and treatment coverage are low. Forecasts should account for planned screening expansion and treatment initiation while avoiding purchases that exceed local capacity to monitor and retain patients.

Important limits and unanswered questions

WHO’s update establishes a policy direction, not evidence that a particular pediatric formulation improves adherence, safety or clinical outcomes. Comparative studies will be needed to determine whether new presentations reduce dosing errors, improve persistence or offer acceptable value relative to quality-assured existing products and validated compounding.

The pivotal trials also do not answer every implementation question. BABY HUG studied infants with sickle cell anemia under trial conditions, while REACH was open-label and enrolled children at specialized African sites. Neither design fully captures routine delivery across all sickle cell genotypes, health systems or adolescence. Affordability, supplier capacity, intellectual-property considerations and manufacturer conflicts will need assessment for each resulting product and procurement arrangement.

Questions clinicians ask

Is WHO recommending a new pediatric hydroxyurea dose?

No. The target product profile addresses the characteristics of an age-appropriate medicine and the access gap it is intended to fill. Clinicians should continue to use applicable product labeling and national or institutional guidance for patient selection, dosing, escalation and laboratory monitoring.

Should treatment wait for a new pediatric formulation?

The profile does not imply that existing quality-assured hydroxyurea should be withheld when treatment is indicated and can be delivered safely. Its purpose is to make future products easier to procure and use, especially where swallowing difficulties or limited compounding capacity impede access.

What should purchasers evaluate beyond price?

Purchasers should assess regulatory status, pharmaceutical quality, dose flexibility, stability, storage requirements, packaging, administration tools and expected waste. They should also determine whether clinics can provide the diagnostic, laboratory and follow-up services needed to convert medicine availability into safe, sustained treatment.

References

1. WHO moves to expand access to lifesaving sickle-cell treatment and care for children — World Health Organization, 2026
2. A multicentre randomised controlled trial of hydroxyurea (hydroxycarbamide) in very young children with sickle cell anaemia — The Lancet, 2011
3. Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa — The New England Journal of Medicine, 2019