Biosimilar development in the U.S. has gained significant momentum over the past year. With last month’s approval of Amjevita, Amgen’s biosimilar of AbbVie’s blockbuster inflammatory disease drug Humira, there are now four approved biosimilars in the U.S.
Although patent challenges may block Amjevita and two of the three other biosimilars from reaching the market for some time, the approvals make clear that cheaper competition is inbound for many leading biologic drugs.
Once it reaches market, Amjevita could begin chipping away at Humira’s impressive revenue stream — some $8.4 billion in U.S. sales last year.
Biosimilars of Amgen’s Neupogen and Enbrel, as well as Johnson & Johnson’s Remicade have already been approved, posing a threat to another $10 billion in combined branded drug revenue (from 2015).
Clearly, biosimilars are taking on some major markets. And continued biosimilar development is a major transformation for the biologics industry in the U.S., which has lagged behind Europe and other markets in permitting biosimilar drugs.
One thing still in dispute, however? What to call them.
A rose is a rose?
Biosimilar brand names, also known as proprietary names, have so far followed the pharma industry’s well-worn tradition of incongruous consonant combinations and softly evoked homonyms. Zarxio. Inflectra. Erelzi. Amjevita.
But the Food and Drug Administration has struggled to decide on how to distinguish between the nonproprietary names of biosimilars and their biologic reference products.
This isn’t a problem for the generic industry. All generic copies of the popular statin Crestor, for example, can be identified by the nonproprietary name rosuvastatin. Each is identical to the other.
Unlike generic drugs, however, biosimilars are not chemically identical to the drug they imitate. Rather, biosimilars are “highly similar," showing no clinically meaningful differences in safety and efficacy.
Since biosimilars are each slightly different than the reference biologic, the FDA has attached a suffix of four consonants to the end of each non-proprietary name to distinguish between the two. Infliximab (Remicade) becomes infliximab-dyyb (Inflectra). Adalimumab (Humira) becomes adalimumab-atto (Amjevita).
In draft guidance for industry published in August 2015, the FDA indicated each suffix should be unique to each product and carry no meaning. As Janet Woodcock, head of the FDA’s Center for Drug Evaluation and Research, explained in a blog post, the naming proposal is designed to prevent inadvertent substitution of biologics and make pharmacovigilance for biosimilar products easier.
Not everyone agrees, however. While PhRMA and BIO, two major trade associations in the space, support differentiated nonproprietary names for all biologics, both disagree that the attached suffix should be meaningless.
PhRMA, for example, recommends the suffix should be derived from the name of the license holder, much like the filgrastim-sndz used for Zarxio, approved several months before the FDA’s naming proposal.
Amgen also supports distinguishable naming. “Assigning a distinguishable nonproprietary name to every biosimilar will help support patient and physician confidence, ensure manufacturer accountability, ensure reliability of supply and create a successful marketplace,” the company said in a statement to BioPharma Dive.
Novartis, on the other hand, believes biosimilars should follow in the tradition of generic drugs. "It is not necessary to modify the existing naming system that has worked well for over 60 years. Biosimilars and interchangeable biologics should share the same non-proprietary name as their respective reference products," the Swiss pharma wrote in a comment on the FDA’s proposal in the Federal Register.
Furthermore, Novartis argues that if a suffix must be imposed, then each company should be given one suffix that is derived from the company’s name. "Evidence reveals that random letter suffixes will not be well remembered, defeating the stated FDA proposes of safety and enhanced pharmacovigilance."
Subject to change
While the debate over suffixes may seem a case of splitting hairs, it is not an insignificant matter to the companies and providers who will be dealing with biosimilar entrants.
All four biosimilars currently approved are not considered "interchangeable" with their reference biologic, meaning pharmacists cannot choose to dole out the biosimilar in place of the biologic — a common practice with generics and small-molecule drugs. A suffix would help differentiate the products to alert providers to the difference. But it would also open the door to new challenges.
In addition to the memory issues raised by Novartis, assigning suffixes to biosimilars could mean all biologics will have to be renamed to include new four-letter suffixes. Indeed, the FDA’s draft guidance proposes to apply the convention to all biologics in order to "encourage routine use" of suffixes and "avoid inaccurate perceptions" of safety based on whether or not the biologic carries a suffix.
The FDA has already put forward a companion regulation which would immediately change the nonproprietary names of six biologics, including Neupogen and Zarxio. Filgrastim (Neupogen) would become filgrastim-jcwp and filgrasim-sndz (Zarxio) would be renamed filgrastim-bflm.
Final guidance on nonproprietary naming is "still forthcoming," according to an emailed statement from the FDA.
In the meantime, "for all approved biosimilars, the FDA has designated ‘placeholder’ nonproprietary names (i.e. ‘infliximab-dyyb’)," the FDA said. These placeholder names would be subject to change if they conflicted with any final guidance the agency issues in the future.
While PhRMA and BIO both support retroactive renaming of biologics (with caution), others in the industry, such as AbbVie, disagree.
The concept of generic drug names is widely accepted and understood by healthcare providers, patients and the public. With biosimilars already suffering from a lack of awareness, nailing a consistent and understandable approach to biosimilar names may be more important than just four letters.