Novartis and Medicines for Malaria Venture (MMV) have announced positive results from their phase II/III CALINA study, demonstrating that a novel formulation of Coartem® (artemether-lumefantrine) developed specifically for babies weighing less than 5kg with malaria has shown good efficacy and safety. The data has been submitted for regulatory review and was presented at the Multilateral Initiative on Malaria 8th Pan-African Malaria Conference in Kigali.
The study addresses a critical gap in malaria treatment, as there is currently no evidence-based treatment available for the smallest babies with malaria. These infants are typically treated with tablets meant for children above 5kg, adjusted by weight, which can lead to overdose and toxicity due to the immaturity of their metabolizing organs.
"We are pleased with the positive outcomes from our CALINA study and to be one step closer to bringing an effective malaria treatment to all age groups, including vulnerable newborn babies," said Shreeram Aradhye, President, Development and Chief Medical Officer at Novartis. "We have been committed to the fight against malaria for more than two decades, and this successful trial represents another milestone towards ensuring that all people have access to an appropriate antimalarial therapy."
A Tailored Solution for the Most Vulnerable
The new formulation, known as Coartem <5 kg Baby, uses a new ratio and dose of artemether-lumefantrine specifically designed to account for metabolic differences in babies under 5kg. The CALINA study is the first evidence-based trial conducted to evaluate a new antimalarial dose and regimen for all infants weighing under 5 kg with acute uncomplicated malaria.
Infants under 5 kg can be affected by placental malaria, leading to poor birth outcomes, or contract malaria from the bite of an infected mosquito. The prevalence of the disease in this age and weight group is poorly understood, and it is therefore often misdiagnosed.
"Infants below 5 kg make up a critical neglected group, and developing antimalarials specifically suited to their needs is essential to malaria control efforts," said Wiweka Kaszubska, Executive Vice President, Head of Product Development, MMV. "The success of the CALINA trial brings us one step closer to ensuring that all patients have access to appropriate and effective treatments."
Study Design and Results
The CALINA study was an open-label, single-arm, multicenter phase II/III study in young infants < 5 kg with uncomplicated Plasmodium falciparum malaria. It evaluated the pharmacokinetics, safety, tolerability, and efficacy of a new dose regimen (5mg:60mg) of artemether-lumefantrine.
The study consisted of a core segment (treatment and follow-up for 43 days) and long-term follow-up at 12 months of age to assess neurodevelopmental status. The trial was conducted across multiple African countries including Burkina Faso, Democratic Republic of Congo, Kenya, Mali, Nigeria, and Zambia.
The primary pharmacokinetic endpoint of the study was met for patients older than 28 days of age. For neonates 28 days of age or younger, although the sample size was too small for a conclusive statistical evaluation, the required value of the pharmacokinetic endpoint was also within the calculated interval.
The key secondary endpoint of lumefantrine C168 concentration was also met for cohort 1 and within range for cohort 2, indicating that the new dose regimen/formulation delivers exposures to artemether and lumefantrine proven to be safe and effective in pediatric patients of higher body weight.
Collaborative Effort to Combat Malaria
The CALINA study is led by Novartis, with the scientific and financial support of Medicines for Malaria Venture (MMV), and as part of the PAMAfrica consortium, which is funded by the European & Developing Countries Clinical Trials Partnership (EDCTP2).
"The CALINA trial is an example of the type of Europe-Africa collaboration we need to close malaria treatment gaps for vulnerable groups, and EDCTP is proud to be part of this endeavor," said Pauline Beattie, Operations Manager and Scientific Advisor, EDCTP Association.
This development comes as Novartis and MMV continue to advance their antimalarial portfolio. In 2021, they reported positive Phase 2b results for ganaplacide/lumefantrine, a novel non-artemisinin combination to treat uncomplicated malaria, which could help address the growing threat of resistance to current malaria treatments.
Addressing a Global Health Priority
Malaria continues to exert a massive burden on public health across the world, particularly in Africa. According to the World Health Organization, a child dies of malaria every two minutes. While significant progress has been made in recent decades in the treatment of malaria, the development of Coartem <5 kg Baby represents an important step toward ensuring that all age groups have access to appropriate antimalarial therapy.
This year's World Malaria Day theme – Health Equity, Gender, and Human Rights – underscores the need to ensure that the youngest and most vulnerable populations have access to the right treatment. If approved, Novartis and MMV aim to make the treatment available as soon as possible to the youngest infants, who currently lack evidence-based treatment options.
The development of Coartem <5 kg Baby builds on Novartis's long-standing commitment to the fight against malaria. Since introducing the first fixed-dose combination artemisinin-based combination therapy (ACT) in 1999, Novartis has delivered more than 1 billion courses of antimalarial treatment, largely at no profit.
