November 18, 2015 at 5:00 am ET
What a difference a name makes for the Federal Trade Commission (FTC) when the Food and Drug Administration (FDA) is doing the naming. The FTC objects to the FDA assigning unique nonproprietary names to biosimilars, the follow-on drugs to off-patent biologic medicines.
It is a battle of the sciences – the dismal versus the medical!
For the FDA’s part, the agency proposes the addition of a four-letter suffix to the nonproprietary name of all biologic medicines, including biosimilars. Such a distinguishable naming convention will promote both accurate prescribing and attribution of adverse events, the agency explained in a draft guidance.
The FTC, responding to the guidance, wants easy substitution of biosimilars for original biologic medicines and each other with price the “salient decision factor,” like it is for generic drugs. The FTC is concerned that distinguishable names would result in “physicians incorrectly (sic) believing” that biosimilars differ in clinically meaningful ways, leading to reduced price competition.
Fact is the physicians at FDA, not the economists at FTC, are correct.
Correct, because of the answer to this riddle-like question: How can a biosimilar, by law highly similar to a reference biologic with which it has no meaningful clinical differences, also be clinically different in a meaningful way?
Answer: When the biosimilar approval is for some, but not all, of the reference drug’s indications, administration routes and/or packaging. By contrast, when the FDA approves a generic drug, it does so for all indications, administration routes and packaging.
Why the difference? Biologic drugs are a lot like Swiss army knives. Typically a protein, combined with sugars and uniquely shaped, a biologic is capable of at least four different therapeutic mechanisms of action against different diseases. Hence, the multiple indications often associated with a reference drug.
To secure a biosimilar approval, a manufacturer submits at least one human clinical study for a single indication. The FDA weighs the study results along with the “totality” of other data to determine biosimilarity for that indication. The agency can then extrapolate the results of that evaluation to approve other indications.
Although the FDA has yet to publish guidance on extrapolation, it is likely the agency will approve extrapolated indications sharing the same mechanism of action of the clinical study indication. However, when other mechanisms of action are involved, the FDA can withhold approval of associated indications if there are clinically meaningful differences.
This is not to suggest a scientific barrier to a biosimilar securing approval for all reference product indications. Rather, it recognizes the considerable difficulty of creating a biologic that is highly similar to a specific reference drug, while ensuring the inevitable and inherent differences are clinically insignificant. Some manufacturers will be able to do it, others will not. Some may seek all indications, others may not.
Because biologic medicines are so complex, developing and manufacturing high quality biosimilars requires deep scientific and manufacturing expertise. It also demands an intimate understanding of the original drug and its function in the body — without access to the original drug’s recipe. A biosimilar can take seven to eight years and $100 to $250 million to develop.
The process for making a biologic medicine is more complicated and involves up to 200 additional steps compared with a chemical drug. Unlike chemical drug generics, which require approximately 50 quality assurance tests, biologics, including biosimilars, require approximately 250 tests to ensure potency, purity, and quality.
When the FDA approved the first US biosimilar, Zarxio (filgastrim-sndz), the agency did so for all indications, understandably because the mechanism of action is similar across all indications. However, in Canada, Health Canada approved Inflectra (infliximab), a biosimilar (or, in Canada, subsequent entry biologic) for Remicade (infliximab) for all indications except those related to Crohn’s disease and ulcerative colitis where the mechanism of action is different.
On the other hand, the European Medicines Agency (EMA) approved the Crohn’s disease and ulcerative colitis indications based on its review of additional evidence. Still, a number of medical societies disagree, refusing to support extrapolated biosimilar use in these indications. They include the American College of Rheumatology, the European CanCer Organisation, the Mexican College of Rheumatology, and the Spanish Society of Gastroenterology.
Who is to say the FDA will follow Canada’s lead, or that of Europe, on biosimilars for Remicade or other multi-indication biologics? Regardless, the agency must preserve its ability to make the scientific call on biosimilarity, indication by indication, through a sound extrapolation process. What the FDA cannot do is follow the lead of the FTC and abandon its support for distinguishable naming.
Distinguishable naming of biosimilars gives practical effect to the FDAs evaluation of indication specific biosimilarity, enabling physicians to prescribe accurately. Otherwise, when a physician prescribes by a uniform non-proprietary name, as more than 50% routinely do for chemical drugs, the pharmacist will decide which biosimilar to select and dispense.
Not a factor in the pharmacist’s selection will be the biosimilar’s approved indications and whether those indications match patient medical conditions and physicians intentions. The pharmacist will not know the patient’s medical status. Instead, economic, not medical, considerations will largely drive the pharmacist’s selection. Frustrated too would be effective and accurate monitoring for adverse events, especially unexpected immune reactions possible with any biologic.
The FTC suggests alternative but inadequate monitoring tools, such as relying on a biologic’s brand name. However, unlike Europe, which requires distinctive brand names, the U.S. has no such mandate, nor does it require prescribers to use brand names. The FTC also suggests the cumbersome approach of relying on proposed World Health Organization (WHO) identifies, which would be stored in databases separate from the nonproprietary name.
Ironically, the FTC is concerned that distinguishable names will inhibit the uptake of biosimilars. On the contrary, distinguishable names will boost prescriber confidence and spur biosimilar use. That’s the difference a distinguishable name makes for biosimilars.
Peter J. Pitts, a former FDA Associate Commissioner, is President of the Center for Medicine in the Public Interest