Biosimilar Naming Decision Nears as Applications Arrive At FDA

Several recent events have ratcheted up the pressure on the Obama Administration to offer some finality on the ongoing naming debate for biosimilars.

The contentious debate on biosimilar naming conventions in the US may soon be reaching a conclusion.

Developments at FDA and in Congress, coupled with a proposal from a global health organization, have come together in recent weeks to set the stage for resolution of the debate over whether biosimilar products should have the same nonproprietary (“generic”) name as the innovator reference product, or be distinguished via some form of prefix or suffix.

Between mid-July and mid-August, Sandoz Inc. announced that the Food and Drug Administration has accepted its 351(k) application for filgrastim and Celltrion Inc. similarly disclosed it had submitted its Remicade biosimilar; Senate Republicans have written to HHS Secretary Sylvia Burwell demanding the immediate release of FDA guidance on biosimilar naming, and the World Health Organization has released a proposal with its recommendations for naming.

Those developments put together ramp up the pressure on the administration and FDA to come to a decision soon. The debate stems around whether to give biosimilars identical international non-proprietary names (INNs) to the innovator product, and if not, how the names should be different.)

Sandoz’ application for filgrastim, a biosimilar to Amgen Inc.’s Neupogen, is the first product to file for approval under the biosimilar pathway created under Biologics Price Competition and Innovation Act of 2009. (Also see "Biosimilar Reimbursement Under The Sequester: The Lower The Price, The Bigger The Spread" - Pink Sheet, 29 Jul, 2014.)

The Sandoz application was filed in May. Given that biosimilars receive a 10-month review, that suggests a user fee deadline sometime before the end of March 2015. That, then, is the de facto deadline for FDA to make a final decision on naming. The policy announcement, however, will probably come sooner.

FDA has developed a draft guidance on naming and HHS is currently reviewing it. The Senate letter from Republican members of the Health, Education, Labor, & Pensions Committee urges HHS to take swift action on the guidance, asking “does FDA intend to approve the first biosimilar before policies on these key scientific questions are publicly released?” (Also see "FDA, WHO Biosimilar Naming Proposals Take Shape" - Pink Sheet, 11 Aug, 2014.)

Generic Pharmaceuticals Association CEO Ralph Neas said that he hopes the guidance will come out soon. “I think everyone is waiting with anticipation… but I don’t think anyone really has any [idea on] timing on when that is going to happen.” GPhA is in the process of looking through the WHO proposal now, and will provide comments before the September 19 deadline.

Balancing Access and Safety

Innovator companies have argued for unique non-proprietary names for biosimilars to assure better post-market tracking of potential adverse events and to assure patient safety. Payors and biosimilar developers have countered that separate non-proprietary names will limit uptake of the new therapies and undercut the competitive case for biosimilars. ( (Also see "The Name Game: Will Innovators’ Latest Battlefront Kill Biosimilars?" - Pink Sheet, 8 Jul, 2013.)

Many generics and biosimilar supporters argue that the current system for naming generics works. They point out that INNs aren’t used for track and trace purposes; the product is identified by its brand name or other codes. In a July 1 letter to FDA Commissioner Margaret Hamburg, thirty-two organizations, including several pharmacies and insurance companies, stated:

“While we agree that it is important to gather data that allows providers to better understand how biologics and biosimilars are performing among various patient groups and to assist in the tracking of adverse events, as we mention above, we believe that the current mechanisms in place (e.g., NDC code, lot number, brand name, manufacturer, etc.) are sufficient. In addition, because adverse events and product recalls for small-molecule and biologic drugs already are successfully identified using the national drug code (NDC code) and lot number, there is no compelling evidence that biosimilars should be handled differently.”

Proponents of the “same name” further argue that calling the follow-on products something different from the innovators will hinder market uptake of biosimilars by confusing prescribers and patients, costing the health care system billions of dollars. In the same letter, they state:

“Moreover, we are concerned that distinguishable names for every biologic, biosimilar, and interchangeable biologic could confuse both providers and patients, and have the unintended effect of slowing the uptake of these cost saving products. Estimates from various economic impact studies predict savings between $42 billion to as high as $108 billion over the first 10 years of biosimilar market formation.”

Another letter to Hamburg from the National Council for Prescription Drug Programs warned that making changes to names would create several operational problems while trying to implement a whole new system. Changes to the current databases would take time and resources, and would “result in confusion, errors, and misunderstanding” during the transition, they argue.

“The compendia groupings are used as the basis for a variety of outcomes many of which will be disrupted if standard nonproprietary naming conventions for determining acceptable “established names” are violated. Each process will have to be individually rebuilt to ensure patient safety and restore functionality to the system.”

Biosimilar sponsors also state that naming biosimilars differently than the innovator undermines the argument that biosimilars are equal to innovator products, while also implying that those products that do share INNs would be considered interchangeable, and therefore tilting the favor toward those companies.

At the February 4 Federal Trade Commission workshop on biosimilars, generic/pure-play biosimilars developers drew a line in the sand on prefixes to distinguish between biosimilars and reference products as a nonstarter but did leave an opening around suffixes.

WHO appears to have used that premise to come up with a compromise approach.

WHO Proposal A Compromise? Only if FDA Agrees

The WHO draft proposal suggests applying a four-letter code called a Biological Qualifier (BQ) to the end of each INN. The four letters would be issued at random so as not to provide any sort of meaning to the suffix, and it would be for all biologics, not just the biosimilars.

Ultimately, WHO does not have the regulatory authority to enforce the naming scheme, but it is an attempt to reach a compromise by allowing INNs to remain the same to avoid discouraging biosimilar uptake, while also providing an instrument to tell which manufacturers made which drug. The name changes would apply both prospectively and retrospectively, but again, the scheme is voluntary.

FDA has a history of using prefixes to differentiate between some biologics.  Sanofi and Regeneron Pharmaceuticals Inc.’s Zaltrap (ziv-aflibercept) for colorectal cancer was given a prefix to differentiate it from Regneron’s Eylea (aflibercept) for macular degeneration. (Also see "Much “Ado” About Biosimilars" - Pink Sheet, 18 Mar, 2013.)

In 2009, FDA announced nonproprietary name changes to distinguish different botulinum toxin products made by different manufacturers—Allergan Inc.’s onabotulinumtoxinA (marketed as Botox), Ipsen’s abobotuinumtoxinA  (Dysport), Merz Pharmaceuticals GMBH’s incobotulinumA (Xeomin)and Solstice Neurosciences Inc.’s rimabotinumtoxinB (Myobloc). The agency explained the reason for the name change was to “emphasize that the different botulinum toxin products are not interchangeable.”

GPhA doesn’t think that regulatory history translates into FDA following the same route for biosimilars, saying that “FDA action regarding a single drug or product category does not represent a precedent, or even a trend. In fact, many more biologics and biosimilars share the same INN.”

The Senate HELP letter to HHS declares that confidential FDA-sponsor negotiations should not be how the naming issue is resolved. “FDA is engaged in conversation with other manufacturers who intend to file biosimilar applications in the future… these meetings should not be the only or primary means by which BPCIA implementation and polices are developed.”

“We still have seen no draft proposal on the naming issue, or guidance on demonstrating interchangeability. We have heard there is some difference of opinion on these matters, making it even more important that these policies … be released in draft form as soon as possible.”

All an HHS spokesperson would say in response to the letter is, “the Secretary appreciates hearing from Members of Congress. HHS looks forward to responding to their letter.”