Pyramax®, a fixed-dose combination of pyronaridine and artesunate co-developed by MMV and Shin Poong Pharmaceutical Co. Ltd., South Korea, is the newest ACT combination to be approved by a Stringent Regulatory Authority. It is the only ACT to be granted a positive scientific opinion under the European Medicines Agency’s (EMA) Article 58 procedure, and is the only ACT to be specifically indicated for the blood-stage treatment of both of the two main strains of malaria: P. falciparum and P. vivax. WHO currently recommends artesunate-pyronaridine in areas where other ACTs are failing.1 Pyramax is also the first Korean product included in WHO’s list of prequalified medicines for malaria and was added to the WHO’s Model List of Essential Medicines (EML) and Model List of Essential Medicines for Children (EMLc) in 2017.
This once-daily, 3-day therapy is indicated for the treatment of uncomplicated P. falciparum and P. vivax malaria in adults and children over 20kg (Pyramax tablets) and in children and infants between 5 and 20 kg (Pyramax granules).
After a restricted label was granted in 2012, via the EMA's Article 58 procedure, Pyramax was assessed in a phase IIIb/IV safety and efficacy study in West Africa (WANECAM) over 4 years to increase the availability of "real life" safety data after repeat dosing. The interim analysis of this study, published in 2016 in Lancet Infectious Diseases2, evaluated the safety and efficacy of Pyramax when administered to patients in the study each time they suffered repeated bouts of malaria over their 2-year follow-up period. The results of the interim analysis, since confirmed by the final results of the study, published in 2018 in the Lancet3 indicated that the safety profile of Pyramax is similar following re-treatment to that seen with initial treatment.
This positive data was instrumental in informing the EMA’s decision to grant a revised label for Pyramax tablets in 2015, removing restrictions on repeat dosing, on use only in areas of high resistance and low transmission, and on requirements for liver-function monitoring. In addition, a positive scientific opinion was granted for Pyramax granules, a child-friendly paediatric formulation. Today, both Pyramax tablet and granule presentations are cross-referenced on the WHO’s list of prequalified medicines, enabling them to be purchased with donor funds.
A large Phase IV real-life study is currently underway in five African countries to evaluate the safety of Pyramax when used in community settings. The CANTAM study completed recruitment in April 2019 with over 8,500 malaria episodes. As of January 2019, 7,363 patients have already been treated with Pyramax in community settings in this study.
In addition, in 2018 a study to evaluate the use of Pyramax in asymptomatic carriers was initiated in The Gambia and Zambia. This study will provide important data to the malaria community - both healthcare providers and policy makers - to inform global efforts to reduce the burden of, and ultimately to eradicate malaria. Its focus is on a population of individuals - currently not well understood - who are infected with P. falciparum parasites, but who display none of the symptoms associated with this serious and debilitating disease. Since these individuals do not have symptoms they rarely seek treatment, but being infected they can still transmit the infection if bitten by a mosquito. The study is assessing the efficacy of Pyramax administered for 3 days, versus 2 days and versus 1 day in clearing a P. falciparum infection in asymptomatic carriers. Results are expected to be available by 2019.
In October 2019, WHO issued an information note on Pyramax stating that “artesunate- pyronaridine can be considered a safe and efficacious artemisinin-based combination therapy (ACT) for the treatment of uncomplicated malaria in adults and children weighing 5 kg and over in all malaria-endemic areas.” The note aims to clarify any perceived discrepancy between the inclusion of the medicine in the WHO list of prequalified medicines for malaria and Model List of Essential Medicines, and the recommendations in the 2015 WHO Guidelines for the Treatment of Malaria, which are expected to be updated in due course.