No new 'mabs' in medicine-New nomenclature for monoclonal antibodies.

Abstract

Monoclonal antibodies (mAb), easily recognisable by the stem ‘-mab’, have transformed the management of many life-threatening diseases, from cancer (e.g., ipilimumab [anti-CTLA4] in melanoma) to autoimmunity (e.g., adalimumab [anti-TNFα] in rheumatoid arthritis) (Bang & Keating, 2004; Lythgoe et al., 2022). Over 100 mAbs have now been approved by the FDA, accounting for 9 of the top 20 global therapeutics by sales, with cumulative earnings exceeding $75 billion (Mullard, 2021). The global therapeutic mAb market is predicted to continue to grow significantly, exceeding $300 billion by 2025, primarily driven by new mAb development (Lu et al., 2020). Naming or nomenclature for mAbs adheres to guidance set out by the United States Adopted Names (USAN) Council and the World Health Organisation International Non-proprietary Names (WHO INN) Programme (Geneva, 2021; Monoclonal Antibodies|American Medical Association, n.d.) The assigned name gives key information about the nature and functionality of the mAb. For example, ipilimumab (named pre-2011) consists of a prefix (-ipi) to permit a unique and distinctive name, substem (1) to indicate target (-lim meaning immunomodulator), substem (2) to indicate source (−u meaning fully human) and a final suffix to indicate functionality (-mab for monoclonal antibody). Over 800 mAb names have now been selected; however, providing new distinguishable names utilising the ‘-mab’ suffix has now become very challenging to nomenclature organisations (Monoclonal Antibodies|American Medical Association, n.d.). In December 2021, a significant update to the nomenclature designation for mAbs has been introduced concordantly by the USAN and WHO INN programme (Geneva, 2021; Monoclonal Antibodies|American Medical Association, n.d.). New mAb names will now consist of a prefix (carrying no specific meaning but should allow unique and distinctive naming), an inflix (indicating target class) and a suffix (denoting class of therapy). Previous guidance indicated use of the suffix ‘-mab’ to indicate mAb class; however, due to the popularity and naming challenges of this therapeutic class, the decision has been taken to replace this by four new suffixes to permit greater distinction (Table 1). Each new suffix has been developed to equally divide substances, which contain an immunoglobulin variable domain into distinct categories (three groups for monospecific immunoglobulins, and one for bispecific and multi-specific immunoglobulins). This new scheme should allow pharmacologically meaningful distinctions, and selection of distinguishable and pronounceable USAN/INNs. Furthermore, this new nomenclature guidance should reduce the requirement for significant future modifications; however, it is impossible to confirm this with absolute certainty. Names that have already been adopted as USAN or INNs will not be retroactively changed, and this new nomenclature will be applied only to new mAbs (Mullard, 2022). In the most recent update, WHO INN List 126 (May 2022), most new monoclonal antibodies conformed to the previous ‘mab’ suffix; however, the first five new monoclonal antibodies utilising this new nomenclature were specified, including crexavibart (antiviral), masavibart (antiviral), nepuvibart (antiviral), paridiprubart (toll-like receptor antagonist) and ogalvibart (antiviral) (International Nonproprietary Names for Pharmaceutical Substances (INN), n.d.). The number of new mAbs affected by this nomenclature change will increase as the new guidance becomes more widely accepted. Education of this nomenclature change is essential for both physicians on the frontline and pharmacologists and other scientists involved in new drug development. Physicians may be used to dealing with potential sequalae from mAb therapy, such as immune checkpoint inhibitor (e.g., ipilumumab) related toxicity in cancer patients, who may be used to easy recognition of mAbs based on suffix ‘-mab’. However, as the average clinical development time for new mAbs is around 6–9 years, the significance of this nomenclature change at the bedside is unlikely to be felt for many years (Lu et al., 2020). As the preclinical development of mAbs precedes clinical testing by many years, and only 10%–15% of mAbs named go on to become approved medicines in the United States or Europe, this change is likely to be of higher immediate importance for pharmacologists and other scientists involved in early drug development (Guimaraes Koch et al., 2022). Appreciating how the nomenclature system for mAbs has evolved over the past decade, and how mAbs, which may have identical targets, sources and functionality, may differ significantly in naming-only based solely on which version of the WHO INN nomenclature system was utilised, will be of high importance when comparing pharmacological characteristics (e.g., pharmacokinetics) and communicating key findings to others. Furthermore, there is a need to educate the doctors and scientists of tomorrow who are likely to be most affected by this change. MPL has received advisory fees from Clovis Oncology outside the submitted work.