FDA’s naming rule for biosimilars has undermined Congress and health care

I recently tried to order white blood cell growth factor (pegfilgrastim) biosimilar for one of my patients. This is a drug that helps prevent fever and infection associated with low white blood cell counts.

For years, prescribing it has been simple, since the only option was the brand-name drug, Neulasta brand pegfilgrastim. But the patent on Neulasta expired in October 2015, and there are now several FDA-approved biosimilars on the market: Fulphila (pegfilgrastim-jmdb), Nyvepria (pegfilgrastim-apgf), Udenyca (pegfilgrastim-cbqv) and Ziextenzo (pegfilgrastim-bmez).

Each is pegfilgrastim but, as required by FDA guidance, each of the biosimilars and the originator itself is further identified by a random four-letter suffix. Even though the intention of Congress was to make biosimilar usage equivalent to that of generic drugs, health care providers are now required to order a specific version, including the suffix. Further complicating the process, prescribers have no idea which version will be covered by a patient’s insurer.

How did we get into this complicated and confusing situation? As part of the Affordable Care Act, Congress passed the Biologics Price and Competition Innovations Act of 2009. This created a new pathway for approval of biosimilar molecules, which are functionally equivalent to their brand name “originator” biologics. These are biologically active macromolecules such as antibodies, receptors, and ligands that are not synthesized chemically but are created in culture by mammalian or microbial cells. Because they are not exact molecular copies, as are generic drugs, biosimilars do not qualify as generic under the Hatch-Waxman Act of 1984.

That may be true under the letter of the law, but I must point out that all biologics undergo minor chemical changes over time — the Neulasta of today is not identical to the Neulasta made a few years ago.

The Biologics Price and Competition Innovations Act created an accelerated approval process for biosimilar molecules that required submission of extensive chemical and manufacturing data plus one clinical trial result for approval of a biomolecule which would be biosimilar in structure and activity to an approved drug that was now off patent protection. Once approved, the biosimilar receives approval for the full range of uses of the originator molecule as stipulated in the “package insert,” and not just the one used in the clinical trial. The goal of this legislation and the subsequent FDA regulations is to substantially cut down on the cost of development of the biosimilar drugs.

Unfortunately, the process has gone off the rails due to concerns about interchangeability (switching between originator and biosimilars) and pharmacovigilance (toxicity monitoring). While state laws or hospital policies may allow a generic to be substituted for a brand-name drug without specific approval from the prescriber, the FDA demanded extra and complex trials to show that the biosimilar and originator molecules could be switched back and forth without loss of clinical efficacy.

Interchangeability may easy to demonstrate for a biologic drug like insulin, for which glucose levels can be monitored hourly, but it would be virtually impossible for cancer or rheumatologic drugs, where the outcome is a clinical benefit demonstrated over months, or even years.

Nevertheless, the FDA now requires all biologics to bear a four-letter suffix in addition to the generic name which would identify it to regulators. There are no data comparing one biosimilar to another, so physicians and pharmacists must assume it works as well as the others. And since each has its own identifier, physicians cannot just order “pegfilgrastim,” but must ask instead for a specific one and know which one will be covered by the patient’s insurance at that moment (which is subject to change at any time without notice).

The suffix also means that each biosimilar is now an individually identifiable drug and the pharmaceutical companies have adopted a strategy of branded biosimilars. This is leading to the proliferation of confusing brand names in addition to suffixes.

A colleague of mine, physician Michael Kane, who directs the oncology pharmacy for RWJBarnabas Health, has told me that this biosimilar system costs our medium-sized health care system about $2 million a year in extra personnel costs, denials of reimbursement, and the need to stock multiple versions of each biosimilar drug to comply with the arbitrary requirements of third-party payers.

Is this really necessary? Is concern over switching from one biosimilar to another in the middle of treatment reasonable? No one knows since none of the companies making oncologic biosimilars have done the interchangeability experiment.

Instead of resulting in a simpler system for prescribing biosimilars, the regulation requiring the use of an identifying suffix has resulted in a plethora of brand names and suffixes for each biosimilar for a biologic coming off patent, creating more work, greater confusion, and less market competition. Instead of all biosimilars competing as one drug pool, there are now five “brands” brands of pegfilgrastim and each competes as a unique agent in the marketplace. Is it any wonder the advent of biosimilars has not resulted in the anticipated savings to the health care system?

This week I was able to finally get pegfilgrastim-cbqv (Udenyca) approved for my patient and covered by the patient’s insurance, but only after multiple phone calls with the insurer. Now I can only hope it will be delivered in time.

Howard S. Hochster is an oncologist, director of oncology research at RWJBarnabas Health in New Jersey, associate director of the Rutgers Cancer Institute, and distinguished professor of medicine at the Rutgers Robert Wood Johnson School of Medicine.