Cethromycin is a ketolide, with 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 or 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 grants from TEDCO Maryland Innovation Initiative. Our research indicates cethromycin has activity against liver stage, blood stage, and dormant hypnozoite stage parasites. Cethromycin reaches high levels in the mouse liver, confirming suitable liver drug levels for dormant malaria therapy. In unpublished communication from a P. cynomolgi study done in 2011 at AFRIMMS by Dr. Greg Deye, one of the two monkey treated with cethromycin did not relapse after 14 days of 16 mg/kg dosing, indicating partial activity or possibly inadequate drug dose exposure. Importantly, this highly desirable multi-stage activity can be attributed to the unique chemical structure of cethromycin, combining the known activity of macrolides against the essential apicoplast organelle, and the potential benefits of the quinoline for enhancing hypnozoite activity.

The unmet medical need is a safe drug against dormant P. vivax or P. ovale, which infect 10 to 50 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 for community acquired pneumonia but was denied approval in 2011 based on lack of superiority over existing pneumonia drugs.

The patent for cethromycin base expired in 2016, so AliquantumRx Inc. developed and patented an improved version of the drug (a hydrochloride salt, HCl) in July 2023, “Salts and Polymorphs of Cethromycin for the Treatment of Disease”, US Patent US20210163522A1. This new drug version has a better solubility and possibly better bioavailability than the original. The novel cethromycin-HCl salt is expected to have better pharmacokinetic profile and hypnozoite activity.

AliquantumRx Inc. is in the process of nationalizing the patent worldwide – Canada, Europe (EPO), Japan, Australia, China, Israel, Singapore, South Africa and South Korea.