Cethromycin is a ketolide, which showed in vitro activity against a number of selected Gram-positive, Gram negative, atypical bacteria and protozoa.
Ketolides are erythromycin A derivatives with a keto group replacing the cladinose sugar and an aryl alkyl group attached to the lactone macrocycle.
Ketolides have extensive tissue distribution, favorable pharmacokinetics (oral, once – a – day) and useful anti inflammatory/immunomodulatory properties.
We have discovered a novel curative oral single dose antimalaria liver stage activity for Cethromycin. The research was supported by a phase I Grand Challenges Exploration award from the Bill and Melinda Gates Foundation, the Johns Hopkins Malaria Research Institute, The Bloomberg Family Foundation, an R21 grant from the National Institute of Allergies and Infectious Diseases and a phase I/II grant from the Maryland Innovation Initiative.
Cethromycin is superior to azithromycin for liver-stage malaria, similar to azithromycin for curative blood-stage and lacks gametocyte-stage activity like azithromycin. The mechanism of action is well defined against the malaria plant-like, chloroplast-like organelle. Pharmacokinetic studies in mice confirm suitable liver drug levels for dormant malaria therapy.
The unmet medical need is a safe drug against dormant P. vivax or P. ovale, which infect 10 to 100 million people each year. Currently, the only drugs licensed to treat dormant malaria – primaquine, and the more recently approved tafenoquine, require a blood test for glucose-6 phosphate dehydrogenase deficiency to prevent a life threatening hemolytic event.
Cethromycin has been used safely in over 5,000 people in phase I-III clinical trials but was denied approval in 2011 based on lack of superiority over existing pneumonia drugs.
A full patent application for the use of Cethromycin to treat liver stage malaria was filed by JHU on Aug. 25, 2015 (PCT/US15/46665). AliquantumRx obtained an exclusive license under all of Johns Hopkins IP rights in January 2019. The license is not a worldwide exclusive as another group jointly worked with JHU on the Cethromycin IP. We have filed a provisional patent application “Salts and Polymorphs of Cethromycin for the Treatment of Disease” on December 2, 2019 to gain worldwide exclusive rights. We also plan novel drug combinations for dormant liver stage activity and other indications. The composition patent for Cethromycin, owned by Abbott and licensed to Advanced Life Sciences Inc., expired in 2016.