The FDA’s Arthritis Advisory Committee voted this afternoon to unanimously recommend approval of Amgen’s biosimilar version of adalimumab (Humira®) for all of its intended indications. Committee members considered the data package provided by Amgen to be comprehensive, but the 26-0 vote was not without some interesting points and drama.
First, it was clear that some members of the Advisory Committee were cloudy as to what a biosimilar actually is. And, surprisingly, one physician asked why Amgen could not use the same cell line used by AbbVie to manufacture their product!
Second, the public comments by patients/advocacy groups, clinicians, and professional societies echoed a call for an extremely cautious approach to extrapolation of indications. Speakers focused on the lack of confidence in our knowledge of the biosimilar product’s mechanism of action (MOA) in inflammatory bowel disease. Regarding the lack of clarity on the MOA in Crohn’s disease, the same is true for Humira. And of course, no one really knows how the data on 6% of the patients taking infliximab applies to those taking adalimumab. Although the Advisory Committee voted for approval unanimously, members of the Committee did take the issue to heart.
Third, public comments voiced great concern about the naming convention (they generally wanted distinct, meaningful suffixes) and “nonmedical switching,” that is, switching mandated or encouraged by health plans, insurers, and pharmacy benefit managers. One comment was to “not let payers usurp FDA’s power” by allowing nonmedical switching. This is truly interesting in that (1) FDA does not determine what managed care organizations cover or how they contract with industry; (2) if FDA does decide to reject extrapolation (which is extremely unlikely in the case of a 26-person consensus), payers could still theoretically encourage off-label use should the incentives be great enough; and (3) the decision to switch is still in the prescriber’s hands, as long as FDA does not designate Amgen’s product interchangeable, which it won’t. One person pointed out that if a payer decides to place a different product, like a biosimilar, in a preferred formulary position, the differential in cost sharing may result in a de facto switch. This may be true, but it is then up to AbbVie to make Humira more attractive/affordable for the payer and patient, so as not to be disadvantaged. That’s what competition is supposed to do.
Fourth, the powerful point was made by FDA representatives that manufactured lots of the innovator product varies by some amount—that the molecules are in fact not identical from one batch to another. Yet those differences are not clinically significant. Certain committee members struggled with the notion that biosimilarity, to some extent, also holds for the innovator product.
In the end, the Advisory Committee voted on the specific question at hand: did the biosimilar’s clinical and analytical data merit approval and use to all of the adult indications, not whether switching should be permitted or regulated, not whether an unknown mechanism of action alters the level of confidence in the drug, and not whether the drug should be named one way or another.