Biosimilar Filgrastim Approved, but With "Placeholder" Generic Name
Efforts to make biosimilar biological products available in the United States passed a milestone on March 6 when FDA approved an agent that is biosimilar to filgrastim, a granulocyte colony-stimulating factor.
Known generically for the time being as filgrastim-sndz (Sandoz Inc.), the biosimilar has the same indications as Neupogen, Amgen Inc.’s 24-year-old filgrastim product.
Similar, Not Interchangeable
Sandoz’s Zarxio is “highly similar” to but not interchangeable with Neupogen, FDA’s John Jenkins said during a media briefing on the approval of the nation’s first biosimilar.
Approval of biologicals as biosimilar products became possible with enactment of the Biologics Price Competition and Innovation Act of 2009. That law also made possible the approval of biologicals as interchangeable products.
“Sandoz did not request approval of Zarxio as an interchangeable product,” Jenkins, director of the Office of New Drugs, told reporters.
But in the five years since the act became a law, FDA has not issued any guidance to companies on how they should demonstrate interchangeability of their biosimilar product with its reference product.
Publication of such guidance, or at least a draft of it, is planned for this year, the agency announced in late February.
Jenkins said the FDA reviewers of Sandoz’s application to market Zarxio concluded that “there are no clinically meaningful differences between it and Neupogen.”
In January, FDA’s external advisers had questioned the results of a pharmacokinetics study that compared the times to recovery of absolute neutrophil count after doses of Sandoz’s and Amgen’s filgrastim products.
But in the end the advisers agreed that the newest filgrastim should be licensed as a biosimilar to Neupogen (see February 15, 2015, AJHP News).
The labeling for filgrastim-sndz has the same information on clinical studies, pharmacokinetics, and adverse reactions, including immunogenicity, as in the labeling for filgrastim.
Jenkins called FDA’s approach for the labeling of the first biosimilar “not that different from the approach we’ve taken in the past for other situations, such as for generic [drug] applications.”
“The prescribing information,” explained Leah Christl, associate director for therapeutic biologics in FDA’s Office of New Drugs, “is there for the prescriber to make an informed decision about whether or not the product is appropriate … to prescribe to a particular patient.”
Information such as the results of the studies to show biosimilarity, Jenkins said, was included in the biological license application to help FDA render a decision, not to help clinicians prescribe the drug.
Something to Consider
Less than a week after the first biosimilar’s approval, Indiana University (IU) Health started preparing itself for this new type of product, said Dawn Moore, vice president and chief pharmacy officer.
The pharmacy and therapeutics (P&T) committee decided to develop a subcommittee that will evaluate how FDA-approved biosimilars “fit into our system” from a clinical standpoint, she said.
A year-old Indiana law allows pharmacists to substitute an FDA-approved interchangeable biosimilar for its reference product if the prescriber has not disallowed the substitution on the prescription.
The law and FDA’s approval of filgrastim-sndz as biosimilar to but not interchangeable with filgrastim, Moore said, means that the subcommittee must carefully word its evaluation of the newer product.
A possible outcome of any evaluation involving a biosimilar, she said, is that the P&T committee declares a “formulary type of parity” and implements a policy whereby the health system preferentially uses one product over the other.
The Indianapolis-based health system earlier evaluated Teva Pharmaceuticals USA’s filgrastim product, tbo-filgrastim, but decided not to use it, she said.
Counting most against tbo-filgrastim, which is not a biosimilar, was the fact that it had only one of filgrastim’s five indications, Moore said.
In addition, the pricing “was not that advantageous for us,” she said, noting that the healthcare setting, such as an outpatient facility, for a product’s use is a factor in a systemwide purchasing decision.
IU Health participates in the federal 340B Drug Pricing Program and can thus purchase many pharmaceuticals for outpatient use at a substantial savings.
“Reimbursement may be another factor in how this plays out with biosimilars as well,” Moore predicted. Third-party payers may decide to set the same reimbursement rate for all filgrastim products, for example.
Sammuel V. Anderegg, pharmacy manager of the oncology service line at Georgia Regents Medical Center in Augusta, said his health system had evaluated tbo-filgrastim and decided not to add it to the formulary as an alternative or replacement for filgrastim.
During the discussion by the oncology P&T subcommittee, he said, most of the concern centered on the lack of data from the pediatric and bone marrow transplant populations. There was also concern about the immunogenicity of tbo-filgrastim.
The labeling for tbo-filgrastim states that the incidence of development of antibodies to the therapeutic protein in patients receiving the product “has not been adequately determined.”
Sandoz included information from the immunogenicity studies of its filgrastim product in the publicly available briefing document for the January meeting of FDA’s advisers. Filgrastim-sndz’s FDA-approved labeling, however, does not have immunogenicity information specific to the biosimilar.
With regard to biosimilars in general, Anderegg said Georgia Regents’ P&T committee will evaluate the available clinical information and discuss whether to add a particular product to the formulary and, if a product is to be added, how that should be done.
“Are we going to approve these in addition to what’s on formulary?” he posed as one possibility. “Or are we going to approve this [specific biosimilar] as a preferred product and take the brand name off of the formulary?”
Perhaps a Temporary Name
FDA chose filgrastim-sndz as Zarxio’s non-proprietary name, calling the hyphenated name a “placeholder” while the agency decides on its “comprehensive naming policy for biosimilar and other biological products.”
But “filgrastim-sndz,” Anderegg said, may be mistaken for “filgrastim” by users of computerized prescriber order-entry systems and personnel in pharmacy storage areas.
“It’s just another four letters at the end of the typical generic name,” he said of the placeholder, and not everyone reads the final letters in a familiar-looking drug name.
In Jenkins’s prepared remarks for the media, the FDA official said the agency intends “in the near future” to issue draft guidance on how companies should name their biosimilar products for the U.S. market.
Not Without a Fight
How soon the biosimilar product will be available for U.S. healthcare professionals to prescribe is unclear.
A lawsuit by Amgen against Sandoz is under consideration by a federal judge.
At issue is whether Sandoz violated a provision of the Biologics Price Competition and Innovation Act, part of the Affordable Care Act.
According to the legal news service Law360, statements made on March 13 by the federal judge presiding over the case put in doubt Amgen’s ability to obtain a preliminary injunction preventing Sandoz from immediately launching its biosimilar product.
[This news story appears in the April 15, 2015, issue of AJHP.]