Clinical Implications of the Recommended Approval of 2 Biosimilars: Interview With Allan Gibofsky MD

In separate meetings earlier this month, the US Food and Drug Administration’s Arthritis Advisory Committee voted unanimously to recommend the approval of 2 biosimilar products: a version of AbbVie’s Humira® (adalimumab) to be produced by Amgen and a version of Amgen’s Enbrel® (etanercept) to be manufactured by Novartis.^1,2 

Several hurdles remain, however, before these drugs can be introduced into the US market. Their manufacturers must first overcome legal challenges by the makers of the original agents, and if and when the drugs do become available, it is unclear to what extent–if any–patients will benefit.

Rheumatology Advisor spoke with Allan Gibofsky, MD, a professor of medicine and public health at Weill Cornell Medical College and an attending rheumatologist at Hospital for Special Surgery in New York, to review the latest developments and how the eventual release of these biosimilars might later impact patient care. 

Allan Gibofsky, MD: If the FDA approves these agents for introduction into the US market, we will see new [patients started] on biosimilars as well as switching of existing patients [to biosimilars]. That will be mandated largely by insurance companies, who will seek to use less expensive options. If an insurance company is covering a particular biologic now, they will be likely to cover the biosimilar, but if they are not currently covering the original biologic, I don’t think they will cover the biosimilar.

It is not clear what the cost will be to payers or whether there will be any difference in acquisition cost to patients–their co-payment will likely remain the same. I don’t expect rules regarding treatment authorization and certification to change, and whatever safety monitoring is in place for the reference product — for infection and abnormal lab studies, for example — that process should stay the same.

Dr Gibofsky: Interestingly, the FDA has yet to approve any biosimilar as an interchangeable product, but interchangeability will essentially occur on the part of the insurance companies. This will very likely apply to all patients, even though interchangeability hasn’t been defined or approved for any of these by the FDA.

Biosimilars are defined as similar to the original product “notwithstanding minor differences” in inactive components. Don’t think of a biosimilar as a generic biologic — unlike a generic molecule, these can’t be bioidentical. I think when the biosimilar market becomes more robust and patients are switched from the original to the biosimilar, there may be differences in efficacy that we won’t know about until after the fact. Even when the pharmacokinetics are the same, the inactive ingredients can be such that patients may experience different efficacy or reactivity, particularly when there are multiple switches.

Dr Gibofsky: They need to be aware of 2 concepts. One is “totality of the evidence,” meaning that the analytical and chemical comparisons have been examined extensively and clarified, so there may still be residual differences but the totality of the evidence suggests they are the same. 

The other concept is extrapolatability: The approval of a biosimilar for one indication allows for the use of the drug in other indications, even ones that haven’t been studied, so you’re going to be using a drug in a patient for whom certain indications have not been studied.³

The physician and pharmacist will also need to know specifically which biosimilar the patient is on, especially when there are multiple biosimilars of the same drug. That’s why the FDA is still discussing a way of naming these agents with unique suffixes, preferably ones that are easily identifiable.

Dr Gibofsky: The discussion will occur at 2 points. One is when a patient is first started on a biologic: Which agent is their insurance company willing to cover? Discussions about biosimilars should include what they are and what their purpose is.⁴ Though they are designed to reduce costs and increase access, that may not apply to the patient, and if their copayment stays the same, they may not understand why. That is a discussion they will need to have with their insurance company.

Another issue is what to tell stable patients when the insurance company says they have to switch to a biosimilar–which is likely to occur. I will tell them that is also a conversation they’ll need to have with their insurance company. 

On one hand it’s good to be an advocate for reduced costs for the system, but we also have to advocate for individual patients. There’s potentially an ethical gray area around switching solely for cost–especially when a patient is doing well on the medication they are currently taking. 

Dr Gibofsky: I don’t think rheumatologists should expect that these products will hit the market any time soon. There is a good chance that litigation and patent expiration will hold up their introduction for several years. Humira, for instance, has patent protection until 2022. Whether it will survive challenges over the next 6 years is not clear, but you can bet the challenges will be made. There are lots of nuances that have to be played out before these agents hit the market in the USA.

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Summary & Clinical Applicability

Though the FDA’s Arthritis Advisory Committee unanimously voted to recommend the approval of biosimilar versions of adalimumab and etanercept, it may take years before the drugs are introduced into the US market, and the anticipated benefits to patients are unclear.

References

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