In this article Dr. Jeff Boden of of the global branding consultancy Kaleio, Inc. details how ibrexafungerp got its name
Authored By: Jeff Boden, Ph.D.
Article Posted: 22 April 2021
Ibrexafungerp is a novel antiungal agent that acts as an inhibitor of β(1-3)-glucan-synthase. The product is differentiated from competitors in the antifungal space through its ability to be dosed orally, engagement of the drug product at a unique enzymatic inhibition site, and its ability to overcome and prevent difficult-to-treat and drug-resistant infections.
The application for a nonproprietary designation was originally submitted to the International Nonproprietary Names (INN) Expert Group at the World Health Organization. Following the initial review of Scynexis’ request for an INN, the INN Experts assigned “ibrexafungin” as the nonproprietary name. The –fungin stem class is defined for “antifungal antibiotics (undefined group)” and modern members of this drug class are echinocandins (e.g., anidulafungin, caspofungin, micafungin). Echinocandins are cyclic lipopeptides with activity against β(1-3)-glucan-synthase. Inhibition of this enzyme ultimately disrupts the integrity of the fungal cell wall via diminished glucan synthesis.
In rebuttal, Scynexis requested consideration of a novel stem to represent their new class of antifungal agents. The Meeting Minutes from the April 2017 INN Consultation further describe Scynexis’ rationale for a novel stem:
“Substances with the -fungin stem are echinocandins, a class of structure represented by six amino acid cyclic structures linked to lipid, and can only be given i.v. In contrast, ibrexafungin was developed for oral administration, is a triterpenoid, and is chemically and biologically different from echinocandins.
Although ibrexafungin acts upon the same enzyme, β(1-3)-glucan-synthase, as echinocandins, it has a different mechanism of inhibition and is believed to bind to the enzyme at a different site. This results in fungal strains that are resistant to echinocandins being highly sensitive to ibrexafungin; indeed, combinations of echinocandins and ibrexafungin have additive activity. A different inhibitory mechanism is also supported by the observation that when specific changes in the amino acid sequence of the enzyme are introduced, they have a differential effect on the inhibitory activity of echinocandins versus ibrexafungin.
From a clinical point of view, doctors could erroneously assume that hypersensitivity and cross-resistance would be the same as for echinocandins, whereas it is not. Having a new stem would make it clear that ibrexafungin represents a distinct family from -fungin substances.”
Scynexis was successful in persuading the INN Expert Group that a novel stem was justified, and ibrexafungerp was ultimately confirmed as a recommended INN. The -fungerp stem was approved by the USAN Council in 2019 and is defined for, “Antifungals, triterpinoids.” This was a major win for Scynexis. The –fungin stem class of compounds contains additional, older, compounds that are not echinocandins and INN could have simply dismissed their request for a new stem and confirmed –fungin as the appropriate stem. A combination of novel molecular structure and efficacy against echinocandin-resistant strains appears to have been enough to convince the committee that a novel suffix was warranted.
Construction of novel name: IBREXA (fantasy prefix) + FUNG (alludes to -fungin mechanism of action targeting β(1-3)-glucan-synthase) + ERP (triterpenoid)
Disclosure: The content in this article from WHO documentation was repurposed with WHO permission.
It would be remiss of me not to include this meme usually otherwise titled “ermahgerd”, which has widely circulated on social media. There are no doubts that ibrexafungerp is a unique and eye-catching name for a drug.
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