Why Biosimilar Drug Names Contain Unhelpful Gibberish
Have you ever wondered how drugs are named? Is there ever a discernible meaning behind drug names? Who manages this mess anyway–drug companies, the FDA or perhaps some toddler with magnetic letters on a refrigerator?
Earlier this year, the FDA released its final rule (PDF here) on how companies should name biosimilar drugs–the large protein molecules that have gone off patent and are made by an entity other than the innovator (the original drug developer). In this case, the agency is asking drugmakers to use letters that have no obvious meaning.
Drug brand names often make no obvious sense at all. Just taking a look at at the 2016 list of the 22 drugs approved by the Food & Drug Administration, we see Eucrisa for atopic dermatitis, Zinplava, a monoclonal antibody to prevent recurrence of Clostridium difficileinfections, and Zepatier, a two-drug formulation for hepatitis C infections.
In other cases, there's some method to the madness. Long-acting bronchodilators or leukotriene inhibitors for asthma often have "air" as part of their name (Advair, Singulair, Cinqair). Exondys 51 for Duchenne muscular dystrophy directs excision of the mutated exon 51 of the gene encoding dystrophin. Aleve (naproxen sodium), a former prescription drug that's now OTC, is used to alleviate pain and inflammation. (For more background on the brand naming process, I refer you to this nice article in STAT News by Mike Pile.)
Generic drug names, officially known as nonproprietary names, are assigned internationally by the World Health Organization and, here, by the United States Adopted Name (USAN) Council. The USAN assigns "simple, informative and unique names" to new drugs that are independent of the manufacturer's brand name. The Council includes representatives from the FDA, American Medical Association (AMA), American Pharmacists Association (APhA) and United States Pharmacopeia (USP).
Drug naming isn't just a wonky issue. Medical and pharmacy students are taught to primarily focus on a drug's nonproprietary name since that's what the drug will always be known as, regardless of manufacturer.
For biologics like monoclonal antibody therapeutics, the USAN has a very systematic approach to naming where each syllable carries interpretable information. Let's take the generic name for the breast cancer drug sold as Herceptin. It's called trastuzumab.
Starting from the right:
"mab" means the drug is a monoclonal antibody
"zu" means the antibody has been humanized from its original source
"tu" means that it's directed to a specific tumor
"tras" is simply a unique prefix to differentiate Herceptin from other "-tuzumabs"
How to name not-really-generic biosimilars
In 2015, the FDA approved the first biosimilar drug in the U.S. The drug, whose brand name is Zarxio, is a version of the white blood cell hormone, filgrastim, made by Sandoz instead of its original maker, Amgen. Amgen sells their filgrastim under the brand name, Neupogen.
Unlike small-molecule drugs, such as ibuprofen and aspirin, a biologic made by a new manufacturer may not be precisely the same as that made by the innovator. First off, the products are 100 to 1,000 times larger–and more complex–than a small-molecule drug. The biosimilars may also have differing additional tags, called post-translational modifications, than the innovator product.
So does one distinguish filgrastim made by Amgen from filgrastim made by Sandoz?
Sandoz, a division of Novartis, decided to use a suffix to reflect their product and gave Zarxio the generic name of filgrastim-sndz. At the time, the FDA was still visiting the topic but -sndz seemed, to me at least, a logical way to differentiate the biosimilar from the innovator product and give information that it was made by a company other than the innovator.
In January, the FDA ruled otherwise, maintaining that while biosimilars should still have a four-letter suffix, the suffix should carry no specific meaning. In their guidance document, they used the examples of replicamab-cxnm and replicamab-hjxf. The drugs share the same core name but differ between the innovators by the content of the suffix.
From the FDA's guidelines, here are the details:
The proposed suffix should:
Be unique
Be devoid of meaning
Be four lowercase letters of which at least three are distinct
Be nonproprietary
Be attached to the core name with a hyphen
Be free of legal barriers that would restrict its usage
The proposed suffix should not:
Be false or misleading, such as by making misrepresentations with respect to safety or efficacy
Include numerals and other symbols aside from the hyphen attaching the suffix to the core name
Include abbreviations commonly used in clinical practice in a manner that may lead the suffix to be misinterpreted as another element on the prescription or order
Contain or suggest any drug substance name or core name
Look similar to or be capable of being mistaken for the name of a currently marketed product (e.g., should not increase the risk of confusion or medical errors with the product and/or other products in the clinical setting)
Look similar to or otherwise connote the name of the license holder
Be too similar to any other FDA-designated nonproprietary name suffix
The issue seems to be the historic stance that a nonproprietary name should be independent of its manufacturer and the conflict that a biologic made by two different companies has notable differences.
Shortly after the final guidance document was released, I reached out to Sandoz/Novartis for their take. The Novartis head of global media relations, Eric Althoff, said, "Sandoz has previously stated that suffixes are unnecessary, however if the FDA required it--we suggest they be meaningful to help to improve pharmacovigilance. We are still assessing FDA’s final guidance issued yesterday and determining next steps. At this point it is too soon to comment further."
But in terms of pharmacovigilance–the process of post-marketing surveillance for adverse reactions–individual drugs already carry a universal product identifier called the National Drug Code (NDC) that identifies the drug manufacturer, the product's dosage form and unit size. It's this NDC number that's most helpful to FDA in tracking adverse reactions to a specific product and product type.
Nevertheless, the two biosimilars approved since Zarxio do indeed carry this noninformative four-letter suffix.
In August 2016, the FDA approved Sandoz's version of Amgen's Enbrel (etanercept). The Sandoz biosimilar is sold with the nonproprietary name etanercept-szzs under the brand name Erlezi.
In September 2016, the FDA approved Amgen's version of AbbVie's Humira (adalimumab). The Amgen biosimilar is sold with the nonproprietary name adalimumab-atto under the brand name Amjevita.
David Kroll, PhD, is a former academic pharmacologist and educator. Follow him on Twitter @DavidKroll or at Forbes.
