By David Steensma, MD | April 2018
ASH Clinical News
Shakespeare claimed that a rose by any other name would smell as sweet. A medication with a confusing name, though, can cause a fatal mistake. That’s why pharmaceutical companies exert so much effort creating clear and distinctive contemporary drug names, sometimes with peculiar results.
The drug-naming process is complicated – with multiple steps and people involved – and is reminiscent of the 1970s “Schoolhouse Rock!” jingle about the gauntlet “just a bill” must travel to become a law.
A promising new molecule developed in a pharmaceutical company lab almost always begins life with an internal letter and number designation, derived from a screening library or a numbered series of chemically similar compounds. The alphabetical portion of this developmental name may reflect the molecule’s mechanism of action (e.g., “Signal Transduction Inhibitor #571” was “STI-571” long before it was “imatinib”). But, more commonly, it is shorthand for the company that developed it; so, LY3009104/INCB28050 is a JAK2 inhibitor developed by Lilly and Incyte, while PF-04449913 is a hedgehog pathway inhibitor developed by Pfizer. (That one raises its hand to “PF-04449913” when the teacher calls roll, but is known to its friends by the less pretentious “913.”)
Molecules that aspire to be drugs also go by lengthy chemical names, which almost no one ever uses, generated using the formal rules of the International Union of Pure and Applied Chemistry (IUPAC). Additionally, they get logged into many different chemical and pharmaceutical databases – the Royal Society of Chemistry’s bizarrely named “ChemSpider,” KEGG (Kyoto Encyclopedia of Genes and Genomes), the Chemical Abstract Service, and so on. Each of these databases uses its own unique identifier system.
Once a drug enters later-stage clinical trials and has a chance of regulatory approval, a good non-proprietary “generic” name is needed, using natural language rather than letters and numbers. This is where things can get interesting.
The Rules of the Name
Just as Adam was tasked with naming the animals in the Garden of Eden, drug companies get first crack at proposing a new drug’s generic name.
Names may be informed by chemical structure and IUPAC name, development history, or mechanism of action. Companies can choose to outsource drug-name creation to a committee or to a specialist naming company such as Miami-based Brand Institute. When I was once a member of a drug name focus group, I heard that the drug that secretly incorporated part of an ex-girlfriend’s name did not make it out of phase I testing due to excess toxicity. I could have predicted that.
I don’t know if God vetoed any of Adam’s animal name ideas, but once a company has made a drug name proposal, a delicate negotiation with regulators ensues. The drug’s name can’t overpromise – we’ll never see a “kurall” or “panaceon,” for instance. Drug names rarely include the name of a disease or a body part, but that seems to be a matter of taste rather than a rule. A drug name shouldn’t mean something in a major language – a lesson Chevrolet learned the hard way with their Nova, which translates to “it doesn’t go” in Spanish. (An apocryphal tale has it that sales of the Chevy Nova were poor in Mexico.) The immunomodulatory (IMiD) drug “lenalidomide” was originally going to be called “cenalidomide,” but cena means “dinner” in Italian, and changes to that recipe had to be made.
Most importantly, generic and brand names should not be easily confused with existing drug names. A drug that improves left ventricular ejection fraction in women will never be called “Cardifem,” because that would be far too easy to mix up with the brand name for diltiazem, “Cardizem.” There are already too many similarly-named drug pairs that can cause problems: sulfasalazine and sulfadiazine, dextromethorphan and dexamethasone, Lamictal and Lamisil, Valtrex and Valcyte, to name a few.
Once chosen, the pharmaceutical company submits newly proposed generic names to national nomenclature committees. In the U.S., the official committee is the five-member United States Adopted Names (USAN) council, housed within the American Medical Association. The International Nonproprietary Names (INN) program of the World Health Organization also creates a unique set of drug names that are globally recognized and, unlike trademarked brand names, public property.
Above all, organizations like USAN and INN are concerned with name clarity, which is why, for instance, drugs that by rights should have an alpha in them (e.g., epoetin alpha or darbepoetin alpha) instead use the seemingly incorrect alfa, since there are far (phar?) more ways to mispronounce ph than f.
Difficulty with ph is also why IUPAC’s a-(N-Phthalimido) glutarimide became “thalidomide” rather than “phthalidomide.” (This name has the side benefit of cutting down on accidental spitting in the clinic when discussing the drug.)
Decoding Drug Names
With new biologics and small molecules, there is often a code that regulates which name fragments or stems will comprise the final drug name. For example, only the ri- is unique to rituximab. The rest of the name tells us that rituximab is an anti-tumor (-tu-), chimeric murine/human (-xi-), monoclonal antibody (-mab).
Most small-molecule tyrosine kinase inhibitors (TKIs) end with -tinib, histone deacetylase inhibitors end with –stat, and proteasome inhibitors end with -zomib. Beyond oncology, we have all the glucocorticoid -onides, proton pump inhibitor –prazoles, anti-lipid -statins, and many other families that share a surname.
There is always room for cleverness like vemurafenib, which targets a V-to-E (ve-) mutation (-mu-) in BRAF V600E (-raf), commonly observed in hairy cell leukemia and certain lung cancers.
Even seemingly complicated names like the newly approved chimeric antigen receptor T-cell product for relapsed/refractory acute lymphocytic leukemia, tisagenlecleucel, can be broken down into their constitutive etymologic parts. The unique component of the name tisa- evokes T cells, but all the rest is formula: –gen implies transfer of genetic material in the CD19/costimulatory construct, –lec– designates selection and manipulation for cell enrichment, –leu– stands for leukocytes, and –cel indicates it is a cellular therapy.
After undergoing all of these naming layers – developmental name, IUPAC name, registry designations, non-proprietary/generic name – a single drug already has as many names as Andrew Lloyd Webber’s Jellicle Cats, even before the marketing people get involved. Unlike generic names, commercial names created by marketers can vary by country and need to be approved by the U.S. Food and Drug Administration (FDA), European Medicines Agency, or other regulatory agencies.
Brand names sometimes seem purposefully designed to be simpler than the non-proprietary names so clinicians will use the trade name preferentially. While physicians can certainly handle long words – seven-syllable hydrochlorothiazide rolls off the tongue for most of us – it is much easier to say the three-syllable “Yescarta” than the nine-syllable linguistic disaster “axicabtagene ciloleucel.” “Synribo” certainly beats “omacetaxine mepesuccinate” hands down. “Lasix” is a brilliant brand name, partly because it conveys the message that the drug’s activity lasts about six hours and partly because it has half as many syllables as “furosemide.”
The same constraints about clarity and connotation also apply to brand names. The FDA worried that the “Glivec,” the European brand name for imatinib, could be confused with a hypoglycemic, so the brand name in the U.S. became “Gleevec.” “Rev-imid” would have been a great name for a “revolutionary new IMiD,” but apparently this sounded too much like French slang for “wet dream,” so an “l” was added, and we now have “Revlimid.”
The preponderance of high-scoring Scrabble letters like x, j, z, and q in brand names is intentional as they connote high-tech and cutting-edge, and are harder to confuse with real words.
Just as diseases are only rarely named after patients – Lou Gehrig’s disease and Münchausen syndrome are on the small list of exceptions – it is uncommon for a person’s name to make it into a drug. But there are a few examples, such as “dasatinib,” named in honor of Bristol-Myers Squibb researcher Jagabandhu Das, PhD, who made key suggestions about its chemical structure at an early stage of development.
Rumor Has It …
Folk etymology is the bane of linguists, who have to explain again and again that woodchucks never had anything to do with lumber, and that a bonfire is not French for “good fire.” These urban legends also plague drug names. Since drug companies don’t have to provide any rationale for the proposal of either generic or brand names, the origin can be quickly obscured.
Where did the ima- in imatinib come from? I’ve been told by several people that because it is the mother of all kinase inhibitors, it was given the prefix ima-, the Hebrew word for mother. I’ve also heard that it means, “I’m a TKI!”, reminiscent of “Hello, My Name Is …” nametags at high school reunions. I was even once told (confidently!) by a colleague that it was named after Chinese-American architect I.M. Pei, because imatinib’s structure fits into ABL kinase as perfectly as a Pei-designed building fits into its surrounding landscape.
Finally, after much barking up dead ends, I learned the truth: Imatinib was initially going to be zimatinib, named after Novartis scientists Jürg Zimmermann, PhD, and Alex Matter, MD, who were crucial to its development. But, USAN frowns on names starting with z or x (and I have to imagine that Coors’ introduction of its beer alternative, Zima, in 1993 was also a strike against zimatinib). So, the z was dropped.
Yet, just as children will always think hamburger has something to do with ham, or that bridegrooms are related to horse grooms, the other stories will undoubtedly persist. You now know better.