Biosimilars: Prepare for evolving landscape, complexities
The new year started with one FDA-approved biosimilar drug on the market and at least five others in the pipeline. The newcomers represent an evolving pharmaceutical landscape for which pharmacists must prepare. At first glance, biosimilars may seem like “generic biologics,” but pharmacists should resist the tendency to see them this way. In terms of regulations, naming, pricing, labeling, and prescribing, the new medications bring previously unseen complexities to the field.
Three types of biologics
FDA recognizes three types of biologic drugs. In addition to innovative biologics (reference products), the agency distinguishes biosimilar biologics from interchangeable biologics.
“With chemical drugs that pharmacists are used to, there’s the brand and there’s the generic, which is typically substitutable. With biologics, there’s going to be three, and the relationship between them is not analogous to that of branded and generic small-molecule drugs,” said Erika Lietzan, JD, an associate professor of law at University of Missouri School of Law.
Biosimilars. Biosimilars, such as the already approved filgrastim-sndz (Zarxio—Sandoz), are similar to the reference product, but FDA does not deem them interchangeable. They can only be approved for indications for which the reference drug is approved, but they do not have to be approved for all of those indications. Likewise, the biosimilar cannot introduce new routes of administration, dosages, or strengths. It can be approved under some or all of the same as the originator product. FDA requires that there be no clinically meaningful differences between the biosimilar and the reference product.
“Right now, it looks like they’re going to have basically identical package inserts, with whatever is not approved being cut out,” Lietzan said.
Interchangeable biologics. For FDA to deem a biosimilar interchangeable with the reference product, the drug must meet the same criteria as biosimilars, in addition to a couple of other measures. The biologic will be expected to produce the same clinical result as the reference product in any given patient. Further, the risk of switching or alternating should be no greater than the risk of using the reference product alone. Currently, there are no interchangeable biologics on the market.
What’s in a name?
Unlike many generic small-molecule drugs, biosimilars will carry brand names just as their originator counterparts do. It’s unclear whether interchangeable biologics will have a brand name.
FDA has not yet finalized a naming framework for biosimilars, but they have proposed that biosimilars and their reference products share the same nonproprietary, or “core,” name. Further, under the proposed framework, for all three types of biologics, that core name will be followed by a four-letter suffix. The only currently approved biosimilar carries a suffix that identifies the manufacturer, as in “sndz” for Sandoz in filgrastim-sndz. Before additional biosimilars gain approval, FDA could institute use of random suffixes rather than manufacturer-specific ones, according to the draft guidance the agency issued this year.
The proposed naming convention has garnered both opposition and support.
APhA opposes manufacturer-linked suffixes. “An ownership change would necessitate a product name change, which could negatively impact patients,” APhA wrote in comments to FDA. The organization also opposes suffixes that distinguish a biosimilar from its reference product. “Using unique nonproprietary names could raise questions about the appropriate use, safety, and efficacy of biologic/biosimilar products, which could lead to clinical and policy decisions that are not scientifically justified,” according to the comments.
Biosimilar pricing is sure to reflect the research-heavy approval process. “Biosimilars will be less expensive than their reference products, but much more expensive than generic small-molecule drugs because the companies have to do a lot of research to support approval, and it looks like biosimilars will be branded,” Lietzan said.
Prescribing and dispensing
Because biosimilars are not interchangeable and have a brand name, they could be prescribed by name. “It won’t be like a prescription for Prozac that the pharmacist automatically fills with generic fluoxetine. In the case of biosimilars, the prescriber will have to specify the biosimilar,” Lietzan said. However, it’s possible, Lietzan added, that payers will require that treatment-naive patients start on a biosimilar rather than an original biologic because of cost.
More biosimilar approvals are expected in the first half of this year. Others are surely on the horizon. “As FDA and other regulators get more comfortable with this and the science has been around longer,” Lietzan said, “I think we’ll see a lot more.”