Novartis and MMV Move to Pivotal Study with New Class of Drug for Malaria
Partners Novartis and Medicines for Malaria Venture (MMV) are moving into Phase III for a combination treatment targeting the rise of artemisinin-resistant Malaria infection, the companies announced Wednesday.
The Novartis compound ganaplacide utilizes a unique, entirely new mechanism of action compared to current antimalarials. When combined with a new, once-daily formulation of lumefantrine, an antimalarial drug currently used, the treatment showed potential to clear normal malaria infection and artemisinin-resistant parasites and block transmissions.
A two-arm Phase II clinical trial included 349 patients older than 12 and 175 patients under 12. In patients with acute uncomplicated malaria due to Plasmodium falciparum infection, the response to ganaplacide/lumefantrine was similar to that observed in patients receiving the "gold standard" artemether-lumefantrine control therapy.
Historically, artemisinin combination therapies (ACTs) have been highly effective in treating P. falciparum malaria. Recent years brought reports from the Greater Mekong subregion of emerging parasite resistance to artemisinin and signs of resistance to the drugs typically combined with it. Infection rates are much lower in this area, so it wasn't a significant concern. However, in the last two to three years, the drug resistant malaria has shown up in parts of Africa, mainly northern Uganda and Rwanda.
"That's a first warning sign we've had," Tim Wells, CSO for MMV, told BioSpace.
"Given that it takes us so long to development, we have to get a move on and get some medicines that don't contain artemisinin out there. If you lose your frontline drugs to resistance, then we would go back to the days of before artemisinin were launched. You'd have maybe a million five children dying every year instead of the current 600,000."
Resistance to artemisinin and the partner drug leads to high treatment failure rates.
In this MMV-backed Novartis combo, the ganaplacide kills the parasite quickly while its partner drug, lumefantrine, hangs around the body longer to clear up any straggler parasites. Ganaplacide's unique mechanism works not only on the parasite's blood stage but also in the liver, potentially indicating some prophylactic activity.
The dosing schedule is optimized at three days like currently prescribed ACTs but at a once-a-day dose instead of two. Wells hopes fewer doses will improve treatment adherence.
"The good news is that we know that the mechanism of action is completely different from anything else that's out there," Wells said.
Researchers are constantly testing primary parasites from multiple African centers to ensure current drugs can work against the newest mutations of P. falciparum. Wells was excited to share, "there are no strains of parasites out there in the field which are resistant to this [ganaplacide]."
Wells projected a timeline of a Phase III trial launch in 2023, with hopes to submit to the FDA in 2025. The study will be extensive and cover multiple countries, predicting where the disease will be and when to maximize trial results.
Novartis has been investing in malaria for over 25 years and has been partnering with MMV since 2007.
"We've been in the game for the long term for malaria," Caroline Boulton, Novartis' Global Program Head for Malaria, told BioSpace.
"I think we share the vision of MMV in trying to really move along that path towards malaria elimination. That's what all of our efforts are around here."
It released the first fixed-dose ACT combo, coartem, in 1999. In 2021, the company reached a milestone of delivering 1 billion drug courses, mainly at no profit. Boulton shared that results are expected in mid-2023 in a trial for a specific infant formulation of coartem, a serious unmet need in the market.
Novartis renewed its commitment to tropical disease and malaria elimination in June with a $250 million five-year commitment to R&D.