Zydus Lifesciences receives DCGI approval to begin Phase III trials of Zintrodiazine, a novel anti-malarial candidate targeting drug-resistant P. falciparum and P. vivax, with prior Phase I data supporting safety and early efficacy.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Zydus Lifesciences has received approval from the Drug Controller General of India (DCGI) to initiate Phase III clinical trials of Zintrodiazine, a novel anti-malarial candidate targeting Plasmodium falciparum and Plasmodium vivax, including drug-resistant strains.
The late-stage program comprises two multi-centre, randomized, assessor-blind, active-comparator studies in India to evaluate the efficacy, safety, and tolerability of orally administered Zintrodiazine in patients with uncomplicated malaria.
The Phase III trial in P. falciparum will enroll 651 patients, while a separate study in P. vivax mono-infection will include 390 patients, with efficacy assessed using PCR-adjusted adequate clinical and parasitological response (ACPR) as the primary endpoint.
Secondary endpoints include recurrence of parasitemia and symptoms due to incomplete parasite clearance, new infections, parasite clearance time, and fever clearance time.
The development of Zintrodiazine comes amid increasing resistance to artemisinin-based combination therapies (ACTs), which remain the standard treatment for malaria. The WHO’s World Malaria Report 2025 notes that partial resistance to artemisinin derivatives has been confirmed or suspected in at least eight countries in Africa.
Zintrodiazine is being developed as part of a combination therapy as a potential alternative to current frontline treatments for both P. falciparum and P. vivax malaria.
Zydus Managing Director Dr. Sharvil Patel described the Phase III approval as an important milestone, highlighting the continued burden of malaria and the growing challenge of resistance to existing therapies, and reaffirming the company’s focus on developing an effective new treatment option.
Zydus has been collaborating with the Medicines for Malaria Venture (MMV) since 2016 to advance a Zintrodiazine-based combination therapy aimed at addressing emerging resistance and expanding treatment options. More than 180,000 malaria cases were reported in India in a recent year, underscoring the ongoing public health need.
Zintrodiazine (also known as ZY-19489) belongs to the triaminopyrimidine class of antimalarials, a newer chemical class with activity against asexual blood-stage parasites. Preclinical studies suggest a potential mechanism involving disruption of parasite haemoglobin metabolism and modulation of the Plasmodium falciparum chloroquine resistance transporter (PfCRT), which may impair parasite survival. Early clinical development includes a first-in-human Phase I study published in The Lancet Infectious Diseases, which demonstrated favorable safety, pharmacokinetics, and preliminary antimalarial activity in healthy volunteers.
Additional early-phase studies, including Phase I and Phase Ib combination trials with ferroquine, have been conducted in small cohorts as part of ongoing development.
Non-clinical studies further support its progression, with preclinical data indicating a favorable safety profile, including no significant effects on growth or neurodevelopment in juvenile models at clinically relevant exposures, supporting further clinical evaluation.
Reference
Bridget E Barber et al, Safety, pharmacokinetics, and antimalarial activity of the novel triaminopyrimidine ZY-19489: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study, pilot food-effect study, and volunteer infection study, The Lancet Infectious Disease, Volume 22, Issue 6 p879-890June 2022, https://doi.org/10.1016/S1473-3099(21)00679-4
Hitesh A Kadu et al, Juvenile toxicity and developmental safety of Zintrodiazine, a novel antimalarial candidate, in Wistar rats, Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag008, https://doi.org/10.1093/jac/dkag008
About the Writer
Nikita Jha, BPharm a pharmacy graduate specializing in medical writing, with a strong ability to interpret complex medical and regulatory information and translate it into clear, accurate, and evidence-based healthcare content. Known for her attention to detail and precision, she focuses on delivering high-quality scientific communication that supports drug safety and informed decision-making.