The presence of misleading information on biosimilars, along with outright false statements, continues to pester the biosimilar industry. This situation repeats the marketing efforts of branded medications in the 1980s as it attempted to fight off the insurgence of generic drugs. And it is very important to note that there are still, 35 years later, people who do not fully accept that generics are expected to provide the same clinical efficacy and safety as the branded drug. No one really expects that only by 2050 will biosimilars be fully accepted. Yet, the longer misinformation exists, the more difficult it will be to gain full acceptance of biosimilars.
Recognizing the problem, the US Food and Drug Administration and the Federal Trade Commission announced a collaboration to combat false and misleading information about biosimilars.
Last week, Hillel P. Cohen, PhD, Executive Director of Scientific Affairs, Sandoz, and Dorothy McCabe, PhD, Executive Director, Specialty Medicine: Immunology, Biosimilars, and CNS, Boehringer Ingelheim, published an important article in BioDrugs that delves into the nuanced types of disparaging and misleading information as well as the context that may contribute to negative connotations of biosimilars. Yes, we just quoted Dr. Cohen on interchangeability in the past week, and have done so many times in the past. He happens to be one of the smartest and quotable experts in the biosimilar arena.
The article by Drs. Cohen and McCabe provided an opportunity to amplify the statements he made at the March 2020 conference announcing the FDA-FTC collaboration.
TOTALITY OF EVIDENCE: TOTALLY CONFUSING?
Unintentionally, the FDA may have contributed a bit to this lack of clarity. The agency has long emphasized analytical, structural, and physiochemical comparisons in the biosimilar review process, and its use of clinical studies only as a validation tool. It relies on the term “totality of evidence” to describe the basis for approval. However, for most people, this term does not describe the types of evidence or the veracity of the data being assessed. In an interview, Dr. Cohen said he actually feels differently: “I happen to think that totality of evidence is a good term. There are simple ways in which it can be explained such as meaning all evidence, not just clinical data. So, while it’s a bit of a challenge, I think totality of evidence is a term and concept that can be explained well.”
EUROPE’S PREVENTIVE TACTICS
Misleading information and false representations about biosimilars no doubt circulate. Some biosimilars such as Sandoz’ biosimilar filgrastim are doing well as the market leader in its category, but at present one class of marketed biosimilars—infliximab—has low marketshare. The rebates offered by Janssen Pharmaceuticals to protect Remicade®’s 85% share accounts for a large portion of this effect. Dr. Cohen cautioned, “We are not claiming in this article that biosimilar disparagement and misinformation is the sole or even primary reason for the slower than anticipated uptake of some biosimilars. We are saying it’s a contributing factor.
With the damage threatened by misleading information, we reflected back on the European experience. Did the European Medicines Agency foresee this to be a problem, and what steps did the organization take to address it? Dr. Cohen explained, that the Europeans took a different approach. “The European Medicines Agency and the European Commission together commissioned two major documents on what physicians should know and what patients should know.” He explained, “They pulled together the EMA, health authorities from individual countries, professional societies, manufacturers, and patient groups.
“It was a multiyear effort, and resulting basic education, background documents were issued maybe five or six years ago; they were actually just recently been updated,” he said. “Then it was the responsibility of each country individually and the professional societies in each country individually to take on biosimilar education. Biosimilar uptake in Europe varies widely from country to country.”
BREAKING DOWN MISINFORMATION
One real value of this article is that it analyzes the types of disparagement and misinformation by type of category:
- Statements about biosimilar science or policy that are factually incorrect
- Misleading information, where the information is correct but is provided out of context
- Incomplete information, where only partial or a limited set of facts are provided
- Creation of a false narrative, especially in scientific and medical literature, that provides a set of references to support incorrect conclusions
- Negative framing of factual statements to create a negative perception
“Unless you understand what’s out there, you can’t begin to counter it,” Dr. Cohen said. “We’ve referred to ‘whisper campaigns’ and we have been talking in general terms about things being misunderstood or aren’t being explained well. From everything that we’ve seen in the past several years, it’s not really just one big category. There are different types and different things that are being said, from flat out incorrect statements (which is not the biggest piece) to negative framing of factual statements.”
He continued, “Negative framing is a very big issue and another one is false narratives. I mean, we’re still hearing people saying the issue of switching from reference biologics to biosimilars is unsettled. [The latest research from Barbieri and colleagues] reviews 178 switching studies and found no new safety or efficacy concerns, and some people still say, “Oh, still not enough.”
Even the language derived from the BPCIA, that use of a biosimilar will result in no “clinically meaningful difference” compared with the reference product contains elements of negative framing. Instead, FDA could frame the language in a positive sense, saying, “it gives you the same safety and effectiveness,” suggested Dr. Cohen.
A MORE RAPID LEARNING CURVE
Returning to the question of when (and how) the general public will understand usefully the place of biosimilars, Dr. Cohen told us, “I would like to think that uptake and acceptance of biosimilar will be more rapid [than generics]. To some degree, if people think of biosimilars as ‘like generics’ but not quite the same, that will provide a decent level of understanding and maybe enable biosimilars to be accepted more quickly.”