Breakthroughs Blog: Malaria

The World Health Organization’s (WHO’s) prequalification (PQ) program plays a critical role in certifying the quality, safety, and efficacy of medical products to expand access to health technologies in low- and middle-income countries (LMICs). In our PQ Pulse interview series, GHTC speaks with stakeholders involved in the PQ process about persistent challenges within this evolving regulatory ecosystem and potential reforms to promote equitable access to innovative medical products.  Our first guest is Pierre Hugo, Vice President of Market Dynamics and Global Supply Security at the Medicines for Malaria Venture (MMV), a nonprofit product development partnership working to advance accessible medicines to treat, prevent, and eliminate malaria. MMV works end-to-end along the research and development pipeline, developing novel products, engaging with regional regulatory bodies, and supporting local manufacturers.In our interview, which has been lightly edited and condensed below, Pierre discusses MMV’s experience navigating WHO PQ and his hopes for the future of the R&D ecosystem.Can you tell us about MMV and the unique role and perspective it brings to product development?We fill the gap and, by and large, are a risk mitigation tool as one of the product development partnerships, or PDPs, within the malaria space to discover, develop, and deliver malaria products. Regarding access, our key ethos is that no drug is a medicine until it's in the hands of the patient. It's all very good and well developing drugs, but if they aren't developed correctly or affordably for the target population and ultimately made available, it's a dead-end game. So, we try to ensure that in the last mile, or the death-mile, drugs are getting to the patients. WHO PQ and organizations like MMV play a very important role.Broadly speaking, how would you describe MMV's experience with engaging in the WHO PQ process?  We’ve got a number of products that are now WHO prequalified, working with our pharmaceutical partners. We see the whole PQ process as a critical mechanism to ensure that quality standards are adhered to and, ultimately, to make quality-assured products available in LMICs, where maybe those regulatory pathways are a little bit less mature. I think what's great to see is that the landscape is changing, with a lot more countries achieving WHO maturity-level 3 status [Editor note: a WHO designation for countries with stable, well-functioning regulatory systems]. Yes, there have been challenges. WHO has been very collaborative, the team has been engaging, and we are grateful for the support that WHO PQ provides.Looking forward, it's going to be critical to see how WHO PQ needs to evolve and change to further strengthen and work more closely with countries’ regulatory mechanisms or pathways.How do you see the regulatory landscape evolving in the coming years, including the potential role of the African Medicines Agency (AMA) and other regional bodies?  The AMA I think is the future; it's critical that it is a success. There's a fair amount of, I wouldn't say pessimism but [questions about] how long it will take for them to be up and running, simply because they just have so many different countries and regional regulatory systems.By and large, the East African collaborative registration or collaborative processes [The Eastern African collaborative registration process is a regional initiative that aims to facilitate the registration of medicines and medical products through a collaborative process, including joint assessments and mutual recognition of regulatory decisions] have been working to some success. There are other regional harmonization networks, but it takes time, and there is still a lot of work that is needed.How do you view recent reforms made to the PQ program? Overall, we are encouraged to see efforts that enable the fast-tracking of innovative product introduction. The new WHO framework for novel products [a reform implemented in 2024 to initiate parallel, rather than sequential, processes for recommending the use of novel products and evaluating them through PQ] is just entering its pilot phase. The new web portal [an online PQ application platform that will provide real-time information for applicants, regulators, and other stakeholders on the status of products in review] will give us greater transparency. The Coordinated Scientific Advice [a new procedure that allows product developers to engage with WHO early on to better understand the evidence that they will need to generate to support PQ review and generation of policy recommendations] should ensure that later review of the finished product is as streamlined as possible.There also needs to be some thought on how AMA will work with the European Medicines Agency, the US Food and Drug Administration, and WHO PQ to avoid complexity for local manufacturers.  If you had a hypothetical magic wand to wave to influence the program, what changes would you make?Something that is critical is to have clarity on timelines and the interaction between PQ and national regulatory bodies and lessons learned. Ultimately, what is the incentive for a manufacturer to go that extra mile to ensure that a product is quality approved [through PQ]? That's where the funders play a critical role in endorsing and supporting the process. Without that support, if you speak to a lot of the manufacturers, they say, “Well, there's no way I'll be going through the WHO PQ process. It's a major investment, and it's an additional long-term commitment that you need to make as a manufacturer.” So, ensuring that there is coordination between normative bodies, funders, procurement partners, and regulators is critical to ensure fast uptake of innovative products.The dream is to have a lot more quality-approved manufacturers in Africa, where over 95 percent of the patient population is. If you look at our new products coming down the line, like single-dose cures or long-acting injectables, greater upfront alignment is key, between WHO PQ and these stringent regulatory authorities, to offer clearer guidance in terms of what those regulatory expectations are for new products. We need to ensure that global procurement agencies, like the Global Fund to Fight AIDS, Tuberculosis and Malaria, the President’s Malaria Initiative, or UNICEF, are working as closely as possible with AMA and with WHO PQ to ensure the rapid uptake of new qualified drugs.I would love to see harmonization between PQ and national regulatory authorities to fast-track important innovation and ensure that new quality-assured drugs get to market faster.Putting on your advocacy hat, where do we, as an advocacy community, need to put our energy in the next couple of years to make some of those improvements become reality?  To unleash the potential [of PQ], we need to simplify the processes for manufacturers, ensure procurement commitments for a clear return on investment, and provide continuous and sustained funding to support manufacturers to embark on the lengthy quality assurance process. If I look at the manufacturers, we did an extensive exercise with the Africa Centres for Disease Control and Prevention to identify manufacturers throughout the whole continent that would want to take malaria products forward to be WHO PQ’d. We only had about 50 manufacturers that were interested in taking part in this initiative [out of 400], so that's a very low number. I mean, we're talking small molecules, not vaccines, and you've got to ask yourself why? They obviously don't see a need to have products WHO PQ’d, which is, on the one hand, a problem. The Africa Centres for Disease Control and Prevention and MMV and other partners believe that the African manufacturing sector can take its place long term alongside manufacturers from India and China, who today supply the vast majority of public health medicines for malaria on the continent.Big Pharma, if anything, is disinvesting in Africa. So, having those in-Africa partners is critical within the malaria space and, obviously, not just for malaria, but for HIV and tuberculosis and so forth.So, I'm just thinking that if manufacturers are going down the WHO PQ route, it might be a really nice carrot to say, “Look, if you are applying for the WHO PQ process, this is a financial incentive in place.” That could be a really nice carrot to keep the Big Pharma guys in the game.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. A research team at the Children's Hospital of Philadelphia has discovered a key process that could provide new insight into designing more effective antimalarial drugs, as rising antimicrobial resistance complicates the ongoing global fight against malaria by rendering current drugs less effective. One promising strategy to combat poor absorption or retention of drugs in the body is the use of prodrugs that can offer a more targeted attack. However, these prodrugs need to be activated, typically by an enzyme. By identifying the primary enzyme that activates multiple antimalarial drugs, these new findings could enable the development of prodrugs for malaria, which, by design, would also be less likely to lead to the emergence of drug resistance.New research shows that wastewater sampling, including in sewer systems and on airplanes, could predict new viral and bacterial outbreaks and the emergence of new variants of pathogens weeks or even months before they become widespread, in addition to being less invasive, more efficient, and faster than current methods. A new study from the US Centers for Disease Control and Prevention demonstrates how it was able to use wastewater sampling to detect the presence of avian flu in 2022 weeks before the virus was detected in poultry and then wild bird populations. Widespread and regular wastewater sampling would enable public health authorities to better surveil population and community health and, on a more micro level, help health care providers provide more accurate diagnoses and care for patients.  Last week, the Pediatric Praziquantel Consortium announced the first administration of its new pediatric schistosomiasis treatment to a preschool-aged child in Uganda, marking a critical step toward closing the long-standing treatment gap for young children for this parasitic disease, which affects millions of children in sub-Saharan Africa. The innovative therapy, designed specifically for children between three months and six years, is also child-friendly, palatable, and heat-stable, making it especially well-suited for this population and region. The rollout is part of a program aimed at integrating the treatment into health care systems and preparing for its broader rollout across the region, starting with Côte d’Ivoire, Kenya, Tanzania, and Senegal.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. Last week, the Gates Foundation, the Novo Nordisk Foundation, and Wellcome announced the launch of the Gram-Negative Antibiotic Discovery Innovator, a new $50 million effort to boost the discovery of new antibiotics for gram-negative bacteria as the global threat of antimicrobial resistance continues to rise and there remains a lacking pipeline of novel antibiotics. The effort will function as a consortium, where multiple funders, research institutions, and industry partners share data and work collectively. Specifically, the project will focus on the discovery of direct-acting small-molecule antibiotics with broad-spectrum activity against Enterobacteriaceae, with Klebsiella species selected as the pathogen to be used in all proposed projects.An innovative, one-dose vaccine designed to offer high-level protection against malaria could transform global malaria efforts if proven effective in further studies. The Sanaria® PfSPZ-LARC2 Vaccine, designed by Sanaria and the Seattle Children’s Research Institute’s Center for Global Infectious Disease Research, uses advanced genetic engineering to delete two critical genes from the malaria parasite, ensuring that the parasite cannot advance to the blood stage and that the vaccine cannot cause or transmit disease. A pivotal study published last month demonstrated the remarkable potential of this approach, and clinical trials are scheduled for later this year.Last week, the Coalition for Epidemic Preparedness Innovations (CEPI) announced $5 million in funding to Ethris to support proof-of-concept research of spray-dried RNA vaccines that remain stable at room temperature and are suitable for mucosal delivery, an approach that could make these vaccines more accessible in low-resource settings and faster to roll out during outbreaks. The spray-drying technique is widely used for other health technologies and applying it to RNA vaccines helps minimize dependence on cold storage and complex delivery systems, especially in low-resource settings. Nasal delivery medicines are also well-established but used with RNA vaccines, this approach could also support their ability to remain stable and could help to offer mucosal immunity, which scientists believe can help reduce virus transmission.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. On World Neglected Tropical Diseases (NTDs) Day last week, the Global Health Innovative Technology (GHIT) Fund announced that it is investing $12.7 million across eight projects to further the development of new technologies to help address NTDs and a range of other diseases. Specifically, the funding aims to further the development of new diagnostics and drugs for leishmaniasis, dengue, malaria, Lassa fever, Rift Valley fever, Ebola, and Marburg, which is being led by various global product development partnerships and companies, including Medicines for Malaria Venture, PATH, and the Drugs for Neglected Diseases initiative.   Newly published research led by the global collaborative endTB project found three new safe and effective drug regimens to treat tuberculosis (TB) resistant to rifampin, the most effective first-line TB antibiotic currently available. These findings help expand the toolkit of treatments for patients with drug-resistant TB in the face of rising resistance globally, offering regimens that are shorter, less toxic, and do not require injections compared to currently available options. The new regimens use two drugs, bedaquiline and delamanid, which have been in use for just over a decade, in combination with older medications. The trial, launched in 2017, involved hundreds of patients across seven countries, including populations often excluded from clinical trials: children, people infected with HIV or hepatitis C, and women who became pregnant while on treatment, ensuring these groups are not excluded from new treatment recommendations.A recently published study found that a prophylactic antibody-based immune therapy protected monkeys against severe disease caused by H5N1 avian influenza, as the outbreak in the United States continues to cause concern. The broadly neutralizing antibody targets a relatively stable region of the virus and is therefore less prone to losing its efficacy than antibodies targeting viral structures that are prone to mutate, helping to ensure that the protection conferred by the therapy can withstand the possible emergence of virus variants. If proven successful in further studies, the therapy could be used to prevent severe disease in at-risk populations and protect first responders and other health care providers in the early stages of an outbreak, and more broadly, this research helps set the stage for the development of medical countermeasures in the case of future outbreaks of influenza.