Since the conception of the biosimilar regulatory pathway in 2010, the term extrapolation has caused confusion and angst for many health system stakeholders. Would the Food and Drug Administration (FDA) approve a biosimilar for all of the reference product’s autoimmune indications, for example, if its clinical studies were in one or two indications only? Mostly, the answer has been yes, with a couple of notable exceptions. We covered this topic back in 2019; since then, Amgen’s rituximab biosimilar was approved, which bridges the rheumatoid arthritis and oncology indications, and the impending adalimumab biosimilar launches have become clearer.
With Amgen’s launch of Riabni® in January 2021, one of the three rituximab biosimilars is approved for all of Rituxan®’s oncology indications and autoimmune indications. None of the adalimumab biosimilars are approved for every single Humira® indication; however, they are approved for the vast majority. In the upcoming case of denosumab, will FDA grant approval for use in Prolia®’s indications (osteoporosis) as well as co-branded Xgeva®’s (oncology-related indications)? Stay tuned on that one.
According to Jeffrey Casberg, MS, RPh, and Leslie Fish, PharmD, both Senior Vice President of Clinical Pharmacy at IPD Analytics, the approval of these so-called “skinny” labels is generally limited by biosimilar manufacturers’ old nemesis, patents. Generally, a drug maker will file patents on additional indications (one at a time) well after the initial composition-of-matter patents are filed. This means, each indication-based patent will expire at sequential dates. “A biosimilar can launch without all the indications,” said Dr. Casberg at the May Asembia meeting in Las Vegas, “if some of the patents on the indication are not yet expired.” Furthermore, agreements to waive patent litigation between biosimilar and reference manufacturers can allow the launch of a biosimilar but without the full slate of indications.
Drs. Casberg and Fish emphasized that this is not related to any clinical or chemical deficiency in the biosimilar. It is simply a legal barrier to full use of the product. The biosimilar has been approved by the FDA to be an acceptable drug equivalent to the reference agent, and as such would be expected to result in the same clinical outcomes. That’s the basis for extrapolation. The implication is that the clinical outcomes for a biosimilar when used in unapproved indications would also be equivalent to those of the reference product.
Payers seemingly understand this point. “More than 50% of insurers are allowing the use of biosimilars for all indications even if the biosimilar does not have the indication,” they said in their presentation. This aligns well with our own continuing market research with payers, with the latest performed more recently to monitor the 2023 adalimumab launches. We’ve found that in more than 70% of cases, medical and pharmacy executives emphasize that if a biosimilar’s cost is significantly less than the reference product, it would make little sense to aggressively manage its use to the skinny label or extrapolated indications only. If the unapproved indication required a different delivery route or formulation, this would not be true. On the other hand, several payers have stated in our research that they will not require special administrative processes to utilize less-expensive biosimilars in the constellation of autoimmune indications.
Adalimumab biosimilars have pretty much the same set of indications, with the exclusion of those that are still patent protected (specifically hidradenitis suppurativa and noninfectious uveitis, which make up a small portion of Humira prescriptions). If a biosimilar is listed as a preferred product on the plan’s formulary, and the prescriber would like to offer adalimumab to a patient with hidradenitis suppurativa, would the plan require the doctor’s office to request Humira use for this specific patient? Not likely. It is just additional administrative work for both, and the biosimilar in this case would still cost less, without any expected difference in outcome.
As Drs. Casberg and Fish said, “This is a legal issue, not a clinical one.”