The Drugs for Neglected Diseases initiative (DNDi) is very pleased to announce the two 2022 Projects of the Year, which recognize DNDi R&D teams and key partners for outstanding progress in the areas of pre-clinical and clinical research. Nominated by the DNDi Scientific Advisory Committee and selected by the DNDi Executive Board, the 2022 awards recognize two projects from among the more than 50 active projects in DNDi’s R&D portfolio.
The partners and staff who collaborate on the 2022 Projects of the Year were celebrated during the WorldLeish7 scientific conference in Cartagena, Colombia, during a special joint convening of the redeLEISH and LEAP platforms, in August 2022.
CpG-D35 project for cutaneous leishmaniasis – 2022 Project of the Year in pre-clinical evaluation
CpG-D35 is being developed as a combination therapy for the treatment of complicated cutaneous leishmaniasis and potentially for post-kala-azar dermal leishmaniasis (PKDL) in partnership with Ajinomoto Bio-Pharma Services (GeneDesign, Inc.) and the University of Tokyo.
Leishmania parasites can persist in host cells by evading or exploiting immune mechanisms. Modulating the immune response with CpG oligonucleotides may improve the effectiveness of chemotherapies in complicated forms of the disease. This project aims to produce an immunomodulator to stimulate the innate immune system and fight parasitic infection as an adjunct to drug therapy.
In 2021, the CpG-D35 clinical programme progressed to first-in-human clinical trials with a single ascending dose study in healthy volunteers initiated and completed in the UK. Overall, CpG-D35 was found to be well tolerated and safe, and none of the criteria for stopping dose escalation were met. Based on these results, plans are underway to progress to a multiple ascending dose study in patients with cutaneous leishmaniasis in 2022.
Miltefosine + paromomycin combination for visceral leishmaniasis – 2022 Project of the Year in clinical research
Since 2010, the first-line treatment for visceral leishmaniasis in Eastern Africa has been a 17-day sodium stibogluconate plus paromomycin (SSG+PM) combination therapy. It is an improvement over the previous 30-day SSG monotherapy, but the treatment is still lengthy and painful, requiring patients to be hospitalized, and has potential toxic side effects.
Based on the good efficacy of the miltefosine and paromomycin (MF+PM) combination therapy in South Asia, DNDi and AfriKADIA consortium partners conducted a Phase III clinical trial in Ethiopia, Kenya, Sudan, and Uganda to assess the safety and efficacy of miltefosine plus paromomycin (MF+PM) as an alternative to the standard of care in Eastern Africa.
The study was completed in 2021 and results published last week showed that the MF+PM combination therapy was as effective as SSG+PM in adults and children but with fewer injections, a shorter treatment duration, and no risk of the potential life-threatening toxicity associated with SSG. MF+PM also reduced the risk of subsequent post-kala azar dermal leishmaniasis, which is a source of ongoing visceral leishmaniasis transmission in communities.
Based on the evidence that it is an equally effective but more patient-friendly treatment, we will disseminate the study results with WHO and countries in East Africa for MF+PM to be adopted as an alternative therapy for visceral leishmaniasis.
‘These two projects represent the significant investments we are making in leishmaniasis. In recent months, DNDi and partners have delivered a number of new treatments using existing medicines for leishmaniasis, while continuing to advance promising new chemical entities through our research and development portfolio,’ said Dr Laurent Fraisse, Director of R&D, DNDi. ‘My heartfelt congratulations and thanks to our partners and DNDi teams for their valuable work and steady commitment to delivering medical innovation for neglected patients.’