In this post Dr. Jeff Boden of the global branding consultancy Kaleio, Inc. details how drugs are named, providing examples and insights.
Authored By: Jeff Boden, Ph.D.
Posted 15 February 2021
My name is Jeff Boden and I name drugs for a living. I am the President of the Nonproprietary Division at Kaleio, Inc., a global branding consultancy. I thought that it would be fun to share some insights into how the newest drug names were constructed. Before we get to that, let me provide some background on how drugs are named.
How Many Names a Drug is Assigned
During a product’s lifecycle, it will typically have 3 names:
- A product code or combination of letters and numbers
- A nonproprietary (generic) name, otherwise referred to as an INN or USAN
- A proprietary (brand) name
Who Assigns Drug Names
Nonproprietary names are assigned, in general, by two groups…
- In the United States, the United States Adopted Names (USAN) Council, part of the American Medical Association, is tasked with the selection of nonproprietary names. These names are referred to as USAN.
- Internationally, the International Nonproprietary Names (INN) Expert Group assigns names to drugs.
Both INN and USAN work very closely with one another to ensure that a single name is assigned to a particular molecular entity or biologic that can be unequivocally characterized by a structure or molecular formula. INN publishes a proposed INN (pINN) list twice a year. This list contains the name, structure, and description of each new drug that was named at either the April or October INN meeting.
The Drug Naming Rules
Drug developers must apply for a USAN and INN, which are required for marketing authorization by FDA and EMA. Most companies submit during Phase 1 or early Phase 2 clinical development because the name approval process takes approximately 2 years to complete. Submitters are allowed to propose up to 6 names in ranked order of preference on the INN application and the names are scrutinized for similarity with existing INN/USAN and brand names.
There are also a slew of written and unwritten rules that nonproprietary names must abide by. One of the most basic is that a nonproprietary name cannot contain the letters H, J, K, W, or Y (except in special circumstances, like when the drug is an interleukin (-kin is the stem for interleukins).
INN and USAN utilize a ‘stem’-based naming scheme for most drugs. The stem is the heart of a name and identifies its mechanism of action. Most stems appear in the suffix position, but they can also appear in the prefix or infix of a name. A “fantasy” prefix, which is intended to be a euphonious letter combination that is devoid of meaning, is combined with the stem to create a new INN or USAN. Also, when referring to an official INN/USAN name or stem in text, it should be italicized, so I hope I did not miss any below for fear of being shamed by my peers! 🙂
Breaking Down Drug Names – Some Examples
Now that you are familiar with the basic regulatory framework, let’s take a look a 5 of the newest drug names from proposed INN List 124.
Special note: I have not worked on any of the products listed below and have not provided any information that cannot be found on the internet.
Action and use: Liver-X nuclear hormone receptor (LXR) beta agonist
Comments: Abequolixron is a first-in-class LXR beta agonist in development by Rgenix. The drug is currently under investigation in a Phase 1 study for patients with advanced solid malignancies and lymphoma. The -lixron suffix (this is a suffix, not a stem, so it is OK that it is not italicized) was clearly created to connote “LXR” and the on suffix connotes the activity of an agonist (i.e., ‘turn on’). This is actually quite a long and strange name for being a first in class drug. Ibrutinib was the first BTK inhibitor to be named and utilized the –brutinib substem with a 1-letter prefix. First in class compounds/biologics usually have some liberty to be shorter than names that fall into a nomenclature scheme that is well established. In this case abequo- is the fantasy prefix, which is 3 syllables, and quite long regardless of product class. For example, the antibody drug class encompasses over 750 names, yet many recent antibodies have only a 2-syllable prefix.
Action and use: Antineoplastic; anti-[Homo sapiens ICOS (inducible Tcell costimulatory, activation-inducible lymphocyte immunomediatory molecule, AILIM, CD278)]
Comments: This antibody is KY1044 from Kymab and is under investigation in a Phase 1/2 study for patients with advanced cancer. This is the 5th ICOS-targeted biologic to be named. Others include feladilimab, izuralimab, rozibafusp alfa, and vopratelimab. It appears to me that Kymab has gotten crafty with their name. The –limab stem indicates that this is an immunomodulatory monoclonal antibody. The alomfi– prefix is supposed to be devoid of meaning. However, it does seem to allude to the target AILIM (activation-inducible lymphocyte immunomediatory molecule). If you are reading this and think that I am crazy, this is how drug names are created and about as close as INN will let you get to identifying the target of your drug in the prefix of your name.
Action and use: serine/ threonine kinase inhibitor
Comments: Defosbarasertib is also known as AZD 2811, which is in Phase 2 clinical development for the treatment of small-cell lung cancer. This is very interesting (to me). Barasertib is a serine/threonine kinase inhibitor that was named back in pINN 102 in 2009. The chemical structure is identical to that of defosbarasertib except that barasertib contains a phosphate moiety (shown below).
INN has defined the fos- stem for “phosphoro-derivatives” and this prefix stem is added to the beginning of drug names that contain such groups. For the most part, phosphoro-derivatives tend to be add-ons to existing drugs (e.g. fosifidancitinib, fosciclopirox, foscarbidopa, fosmanogepix, etc.). In this case the opposite has occurred. Here the parent drug product contained the phosphate and the new variation has removed it. Because the originally named barasertib should have been named FOSbarasertib, INN had to get creative when associating the structural relationship between these two compounds. This time around they have used the defos- prefix to identify the removal of the phosphate group in defosbarasertib. It is important to note that the defos- prefix has been used once before in a recommended INN. Defosfamide was assigned in 1962, back when most drug names were based on chemistry. In this case the defos- prefix likely was referring to “phosphorodiamidic acid.” As you can see, citing past precedent will not always get you where you want to go in drug naming as the nomenclature is constantly evolving.
4. eflimrufusp alfa
Action and use: EGFR1/VEGFR2/FGFR1-Fc-fusion protein; angiogenesis inhibitor
Comments: It is not apparent which company is developing this fusion protein, but Google patents suggests that it might be RemeGen’s RC28. This one might look pretty weird but if you understand the fusion protein nomenclature scheme, it is actually self-explanatory. The fusion protein nomenclature scheme was defined in 2018 and reserved for use in naming multifunctional proteins derived from a single nucleotide sequence, which may contain two or more genes, or portions of genes, with or without amino acid linker sequences. In addition to the suffix –fusp, a syllable formed from a one consonant and one vowel are added before the suffix to indicate: (a) consonant – the pharmaceutical action; and (b) vowel – the targeting. In eflimrufusp we have -RU-, indicating that this is a receptor/untargeted fusion protein. But that’s not all! Ef– is a prefix stem for Fc-fusion proteins and according to the fusion protein nomenclature scheme, in a multifunctional fusion protein that has more than one pharmacological action, but also contains a stabilizing Fc fragment, both ef- and -fusp should be used. And that’s how we get to eflimrufusp. The -lim- infix is the only “fantasy” part of this name, but it is actually somewhat misleading because -lim- has traditionally been used as an infix stem in the monoclonal antibody scheme to identify immunomodulatory antibodies… But I digress. Alfa has been added as a second word to identify that the protein is glycosylated. If another developer comes along with the same protein with a different glycosylation profile, that product will receive ‘beta’ as a second word.
5. exagamglogene autotemcel
Action and use: Genetic modification, which disrupts the binding site for the GATA1 transcription factor
Comments: Again, not entirely clear who owns this but I’d bet that it is CTX001, in development by CRISPR Therapeutics for the treatment of hemoglobinopathies. This product consists of autologous CD34+ stem cells that have been genetically modified using CRISPR/Cas9 gene editing. Targeted disruption of the erythroid lineage-specific enhancer region of BCL11A via site-specific cleavage causes a double strand break. The break is subsequently repaired by nonhomologous end-joining (NHEJ), leading to the transcriptional repression of BCL11A. BCL11A is a repressor of γ-globin gene transcription. Therefore, induction of γ-hemoglobin expression is a potential strategy to treat patients suffering from hemoglobinopathies.
Exagamglogene autotemcel is a genetically modified cell therapy and therefore has a 2-word name, where the first word identifies the genetic manipulation and the second word identifies the cell type. –gene is the common stem that is assigned to all gene therapies. This stem is preceded by a defining infix that specifies the exact gene that is expressed. In this case, the CRISPR/Cas9 editing enhances the expression of the γ-globin gene. The -gamglo- infix has been utilized to identify γ-globin. Previously, other gene and cell therapy products have been developed that introduce a functional copy of the β-globin gene, and these have been assigned the -beglogene suffix. So you can see how -gamglo- and -beglo- are representative of γ− and β-globin, respectively. Exa- is the fantasy prefix.
For the second word, autotemcel is used to identify the cells as autologous stem cells. The auto- prefix was designated for autologous cell-based gene therapies in 2019 to avoid oversaturation of the cell therapy naming space. INN decided that there was little utility in assigning fantasy prefixes to autologous cells as they are specific to each individual patient. However, allogeneic cells and non-genetically modified autologous cells are assigned distinct prefixes.
Action and use: Enoyl-acyl carrier protein (ACP) reductase (FabL)
Comments: Nilofabicin, or CG-549 (CrystalGenomics) is a potential first-in-class antibiotic targeting ENR (Enoyl-acyl carrier protein reductase) or FabI (Fatty acid biosynthesis type I). According to CrystalGenomics’ website it is being developed to target MRSA (Methicillin Resistant Staphylococcus aureus) and VRSA (Vancomycin Resistant Staphylococcus aureus) and is currently under investigation in a phase 2a study in the United States.
The -fabicin suffix clearly connotes the activity of this class of antibacterial as a FabL inhibitor (fab + icin). This suffix is not yet an official INN/USAN stem but may be added to the stem list in the coming years. This suffix has been used once before in afabicin (named in 2015, Debio 1450; has completed a Phase 2 study in Acute Bacterial Skin and Skin Structure Infections (ABSSSI), which highlights my previous point about first-in-class names tending to have shorter prefixes. In afabicin, the prefix is simply ‘a’. The fantasy prefix in nilofabicin is ‘nilo’ and any future member of this mechanistic class of antibacterial agents should expect to receive a prefix of at least two syllables. Targeting the activity of ENR may prove to be an effective and novel means to treat MRSA and VRSA infections by disrupting fatty acid biosynthesis. Because FabL is present only in bacteria, there should be minimal side effects associated with this drug.
ABOUT THE AUTHOR
Dr. Boden leads all Nonproprietary (INN/USAN) naming projects for the organization. He is an expert in the policies and procedures of the INN Expert Group and USAN Council and, in total, has submitted over 1000 nonproprietary naming applications; more than anyone in the world. Prior to joining Kaleio he served as Vice President of the Nonproprietary Naming Division at Brand Institute and led all related operations of the company from their Miami headquarters. In addition to his work in Nonproprietary Naming, Dr. Boden has previously held positions in pharmaceutical R&D for Alkermes, Integene, and Goodwin Biotech. He earned his BA in Biology from the College of the Holy Cross and has a PhD in Cancer Biology from the University of Miami.
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