A HPBCD solubilized novel fusion inhibitor of influenza virus was found orally active in mice

Posted by

A group of researchers employed by different subsidiaries of Janssen Research & Development, Scripps Research Institute, Department of Epidemiology, as well as Harvard T.H. Chan School of Public Health recently published their results on the efficacy of a new chemical entity encoded JNJ4796 in preclinical studies in Science magazine.

JNJ4796 is a piperazine derivative developed for influenza virus inhibition. The in vivo pharmacokinetic (PK) profiles of the compound was evaluated in mice (the compound was formulated as a 0.25 mg/ml solution in 20% w/v HPBCD for intravenous administration, while the substance was administered per os formulated as 1.33 mg/ml solution in 20% w/v HPBCD).

JNJ4796 protected mice from lethal challenge of 25 times the median lethal dose
(LD50) of H1N1 A/Puerto Rico/8/1934 virus. Doses of 50 and 10 mg/kg of JNJ4796 twice
daily, initiated one day before challenge and continuing for 7 days, resulted in 100% survival at day 21.

Besides this impressive efficacy it is also notable that cyclodextrin was employed right in the early phase of drug development. Consequently PK, dosage regimen, and safety data will be inseparable from the fact that a cyclodextrin-enabled form of the active was applied. Even without direct evidence it may be assumed that the well-known solubilizing and permeation-enhancing effect of CD was manifested in the success of the experiments in one way or the other. Therefore all experimental data generated with the CD-formulation will be a ‘gold standard’ for the later stages of development, especially due to the planned oral delivery of the drug candidate.


van Dongen et al., Science 363, eaar6221 (2019)

patent application WO2018141854: Piperazine Derivatives For Influenza Virus Inhibition

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.