The European Medicines Agency (EMA) has recommended two drugs for the treatment of schistosomiasis and sleeping sickness for use outside of the European Union. The medicines were submitted through a procedure known as EU Medicines for All (EU-M4All), which enables the EMA, in cooperation with the World Health Organization (WHO), to provide scientific opinions on high-priority human medicines that are intended for markets outside of the European Union.
A rpraziquantel was recommended for the treatment of schistosomiasis in younger children aged 3 months to 6 years. It is derived from praziquantel, the standard treatment for schistosomiasis developed in the 1970s, and is the first medicine specifically formulated for preschool-aged children.
Fexinidazole (Fexinidazole Winthrop) is used to treat human African trypanosomiasis, or sleeping sickness, caused by Trypanosoma brucei rhodesiense. It is the first oral treatment for the acute form of the disease in adults and children aged 6 years or older who have a body weight ≥ 20 kg (44 lb).
Bilharzia: Thousands of Deaths Every Year
Schistosomiasis, a neglected tropical disease also known by the name bilharzia, stems from blood flukes (trematode worms) that inflict long-term damage to organs such as the bladder, kidneys, and liver. The disease is found throughout Africa, and in parts of South America, the Caribbean, the Middle East, and Asia. More than 250 million people required preventive treatment for schistosomiasis in 2021, with an annual toll of at least 20,000 deaths. Schistosomiasis can have severe consequences in children, including impairment of physical and cognitive development, and the lack of a suitable pediatric formulation has limited the ability to control the disease.
Arpraziquantel induces muscular paralysis in the schistosome worms, causing them to loosen their grip on mesenteric vein walls. They migrate to the liver and are eventually destroyed and eliminated. The positive opinion is based on supporting evidence from phase 2 and phase 3 clinical trials, including the results of the phase 3 trial in Côte d’Ivoire and Kenya, demonstrating the safety and efficacy of arpraziquantel, leading to cure rates of 90% or higher.
The development of arpraziquantel was driven by the Pediatric Praziquantel Consortium, with funding through the European and Developing Countries Clinical Trials Partnership (EDCTP) and the Japan-based Global Health Innovative Technology Fund.
Human African trypanosomiasis is a potentially fatal disease transmitted by infected tsetse flies found in 36 African countries. It manifests with neuropsychiatric symptoms that disrupt sleep patterns and can lead to death. The EMA recommendation covers both first-stage (hemolymphatic) and second-stage (meningo-encephalitic) Tb rhodesiense sleeping sickness, a severe and lethal form prevalent in Eastern and Southern Africa, and follows positive results from clinical trials conducted in Malawi and Uganda by the Drugs for Neglected Diseases Initiative (DNDi), supported by the EDCTP through the HAT-r-ACC consortium, which brings together partners with expertise in sleeping sickness.
Data from DNDi’s phase 2/3 clinical trial, presented recently at the European Congress of Tropical Medicine and International Health, demonstrated the high effectiveness and safety of fexinidazole against Tb rhodesiense sleeping sickness. Over 12 months of follow-up, only one patient with the advanced form of the disease relapsed, requiring treatment with the standard arsenic derivative.
EU Medicines for All
“The regulatory pathway was introduced in 2004 as part of a wide-ranging set of reforms to the EU pharmaceutical legislation,” Martin Harvey Allchurch, head of international affairs at the EMA and in charge of EU-M4all, told Medscape Medical News. “It stemmed from increasing interactions between WHO and EMA and reflected realization of the global health impact of the agency’s scientific assessments.”
He added that the first products through the pathway were for HIV/AIDS. “These were products that had been approved for use in the EU, but for which there were significant public health needs outside of the EU,” he noted.
The impact of the initiative on healthcare delivery and patient outcomes was reviewed in 2019, and the findings were published in the Expert Review of Clinical Pharmacology.
“At the time of publication, there had been 10 positive opinions under the pathway, but these had resulted in 138 regulatory approvals in 90 countries: 75 approvals in Africa, and the remainder in Latin and South America, Middle East and Southeast Asia, and non-EU Europe and Central Asia,” said Allchurch.
“The latest figures I have from earlier this year — based on 15 positive opinions — is that 158 regulatory approvals had been granted in 93 countries, largely reflecting the same geographic spread,” he added.
Commenting on how the EU-M4All scheme has evolved over the years, Allchurch explained that since 2021, the procedure can also be performed in parallel with a centralized procedure to accelerate medicine accessibility at a global scale. The scheme has also widened its criteria to include any product type (including generics) and therapeutic area, provided that the EMA and WHO agree on its eligibility.