Novartis malaria treatment Coartem® Baby receives WHO prequalification, paving way for greater access for newborns and young infants

WHO Prequalifies Novartis' Coartem Baby for Newborn Malaria

Novartis announced that its malaria treatment, Coartem® (artemether-lumefantrine) Baby, has received World Health Organization (WHO) prequalification. This marks the first and only antimalarial specifically developed for newborns and young infants weighing 2 to 5 kilograms, addressing a long-standing treatment gap. The prequalification is a crucial step for enabling widespread access through public sector procurement by UN and other agencies. Novartis plans to make the treatment available on a largely not-for-profit basis in malaria-endemic regions, with initial introduction already in Ghana, aiming to reach more vulnerable patients.

• Coartem Baby fills a significant unmet medical need, being the first and only antimalarial specifically formulated for infants weighing 2 to 5 kilograms. Previously, infants under 4.5 kg lacked an approved treatment, often receiving formulations intended for older children, which carried risks of side effects and toxicity. This new formulation ensures appropriate dosing and improved safety for the smallest malaria patients.
• WHO prequalification is a vital milestone that enables United Nations and other procurement agencies to fund and purchase Coartem Baby for public sector distribution. This process assesses the quality, safety, and efficacy of treatments, ensuring that the medicine meets international standards. Novartis is committed to making the treatment available on a largely not-for-profit basis in regions where malaria is endemic, significantly expanding its reach.
• Coartem Baby was developed through a key collaboration between Novartis and Medicines for Malaria Venture (MMV), with additional support from the PAMAfrica consortium, co-funded by the European & Developing Countries Clinical Trials Partnership and the Swedish International Development Cooperation Agency. This partnership highlights a successful model for translating scientific innovation into real-world public health impact, ensuring that even the most vulnerable patients are not left behind in the fight against malaria.

WHO Prequalification: A Milestone for Infant Malaria Treatment

Over the past three years, several critical populations have been identified as key targets for malaria interventions, reflecting persistent gaps in prevention, treatment, and control efforts. Children under 5 years remain the most vulnerable population, with targeted interventions including spatial repellent devices like transfluthrin-based Mossie-GO™ in Uganda, and continued challenges in Nigeria where this age group faces high morbidity and mortality despite available interventions. Northern states in Nigeria report the highest malaria prevalence among children, with rural areas disproportionately affected, while countries like Cameroon have focused on rollout studies for the RTS,S/AS01 malaria vaccine targeting children aged 11-30 months.

Pregnant women represent another critical target population, particularly in sub-Saharan Africa where intermittent preventive treatment in pregnancy (IPTp) coverage remains suboptimal. Studies across 20 sub-Saharan African countries revealed that only a median 3.9% of women completed eight or more antenatal contacts, significantly limiting access to preventive interventions. In the Democratic Republic of Congo, which accounts for 12% of global malaria cases, pregnant women face malaria in pregnancy prevalence rates between 17% and 40%, with a concerning 26% asymptomatic pooled estimate creating silent transmission reservoirs. The situation is particularly dire in conflict zones of Eastern DR Congo, where armed conflict has decimated infrastructure, leading to critical shortages of insecticide-treated nets and intermittent preventive treatment.

Geographically vulnerable populations have been identified through micro-stratification studies, revealing specific high-risk areas requiring targeted interventions. In Nepal, approximately 100,000 people representing 3.62% of the country's total population live in high-risk areas, with the Far- and Mid-western regions containing the majority of high-risk villages. Thai-Myanmar border populations continue to be targeted due to importation of infections complicating elimination efforts in Thailand, while Sumba Island in Indonesia experiences high transmission rates driven by multiple Anopheles mosquito species. Resource-limited areas face compounded challenges, with public health systems struggling to adapt to climate change impacts on malaria transmission, fragmented coordination, funding gaps, and emerging artemisinin resistance hindering implementation of promising innovations including diagnostics, vaccines, and surveillance systems.

Closing the Long-Standing Treatment Gap for Newborns

Current malaria treatment faces significant obstacles that threaten global control efforts and patient outcomes. These challenges span drug resistance, vaccine development limitations, and complex biological factors that complicate therapeutic approaches.

• Drug resistance represents the primary treatment challenge, with Plasmodium falciparum developing resistance to all current antimalarial options, including chloroquine-resistant strains emerging in most malarious areas and artemisinin resistance documented in Southeast Asia with prolonged parasite clearance times

• Vaccine development remains elusive despite decades of research, as traditional vaccination methods have proven unsuccessful for malaria unlike other eradicated diseases, with specific vaccine candidates like Pfs48/45 hindered by poor expression in both prokaryotic and eukaryotic hosts

• Complex parasite biology creates significant therapeutic barriers, including a 48-hour life cycle with synchronized replication, variation in immune recognition and drug action across different life cycle stages, and intricate interactions between parasite dynamics, host immunity, and drug effects

• Drug discovery and screening present substantial technical challenges, requiring screening of 1-2 million compounds per campaign across multiple stages before pre-clinical trials, with in vitro antimalarial screening complicated by assay variability across laboratories globally

• Regional resistance patterns are rapidly evolving, with Southeast Asian artemisinin and partner drug resistance potentially causing an additional 78 million cases over five years if spread to Africa, while surveillance data from multiple regions show increasing frequencies of resistance markers to key antimalarials

• Multi-drug resistance is expanding geographically, with therapeutic failure rates reaching 83.1% for chloroquine in India-Myanmar border regions and 95.4% of P. falciparum samples in Papua New Guinea carrying resistance alleles to either Fansidar or chloroquine

The Global Burden of Malaria and Access for Infants

Recent global malaria data reveals significant regional variations in disease burden, with the most comprehensive estimates coming from the Eastern Sub-Saharan Africa region for 2023. Among women of reproductive age in this region, Mozambique reported the highest prevalence rate at 19,627 cases per 100,000 population, while Eritrea had the lowest at 842 cases per 100,000. For incidence, Mozambique also led with 16,076 new cases per 100,000 women of reproductive age, compared to Eritrea's 2,267 new cases per 100,000. Despite these high numbers in certain countries, the region showed substantial reductions in both prevalence and incidence rates in 2023 compared to 1990 baselines, with exceptions noted in Djibouti and Ethiopia.

Global burden analysis from 1990-2021 data demonstrates that malaria dominates vector-borne parasitic diseases, accounting for 42% of all cases and 96.5% of deaths within this disease category. The Eastern Africa region specifically experienced significant improvements over this period, with malaria incidence rates decreasing by 54%, prevalence by 61.8%, mortality by 62%, and disability-adjusted life years (DALYs) by 63.8% from 1990 to 2021. However, regional disparities persist, with South Sudan recording the highest age-standardized incidence and prevalence rates in 2021, while Uganda had the highest mortality and DALY rates.

Country-specific data from recent years shows considerable variation in malaria burden across endemic regions. Tanzania reported an 8% prevalence among children aged 6-59 months, with regional variations ranging from below 1% in some areas to 23% in Tabora region. In contrast, Ethiopia's Enor-Ener Woreda showed a 21.1% prevalence among febrile children under five years, while Rwanda's Ngoma District recorded a 61.2% prevalence among febrile patients aged five years and older. The disease burden remains most concentrated among children under five years globally, with DALYs peaking in neonates aged 7-27 days, highlighting the critical need for targeted interventions in this vulnerable population.

Closing the Treatment Gap for the Smallest Malaria Patients

The World Health Organization's prequalification of Novartis's Coartem® Baby marks a significant milestone in the global fight against malaria, particularly for the most vulnerable populations. For years, a critical treatment gap has existed for newborns and young infants weighing between 2 and 5 kilograms, a demographic highly susceptible to severe malaria with limited dedicated therapeutic options. Existing artemether-lumefantrine formulations are typically indicated for patients weighing 5 kg or more, and adapting doses for smaller infants presents considerable challenges due to their unique physiology and the risk of either underexposure, which can foster resistance, or overexposure, leading to toxicity. This new, specialized formulation directly addresses these concerns, promising more precise and safer treatment for the smallest patients.

The WHO prequalification is not merely a regulatory nod; it is a powerful catalyst for widespread access. It enables public sector procurement by UN agencies and national governments, facilitating the distribution of this life-saving drug in malaria-endemic regions, often on a not-for-profit basis as planned by Novartis. This model is crucial for overcoming the historical barriers of affordability and ensuring equitable access, which have previously seen effective treatments remain out of reach for many due to price disparities between public and private sectors.

However, the path forward is not without its complexities.

• The persistent threat of artemisinin resistance, evidenced by the expansion of specific genetic mutations and the detection of residual submicroscopic parasitemia after treatment in some areas, necessitates continuous vigilance and robust surveillance.

• Operational challenges in distribution, ensuring adherence to diagnostic testing before treatment, and improving dispensing practices remain critical. Studies have highlighted issues such as inadequate explanation of dosing regimens and the continued dispensing of antimalarials without prior parasite confirmation.

• While artemether-lumefantrine demonstrates high efficacy, some evidence suggests that other artemisinin-based combination therapies may offer prolonged protection against recurrent malaria, particularly in high-transmission settings. This raises considerations for long-term malaria control strategies in infants, where preventing re-infection is paramount.

Ultimately, Coartem Baby represents a vital step towards eliminating malaria-related mortality in infants. Its success will hinge not only on its availability but also on concerted efforts to ensure appropriate use, combat resistance, and strengthen health systems to deliver this crucial intervention effectively to every child who needs it.