Maia Kayal, MD, MS, and Jonathan Kay, MD, define interchangeability and review the details of a switching study.
Ryan Haumschild, PharmD, MS, MBA: With all those different options, we know some of the details that are starting to emerge is the term interchangeability. We need to understand interchangeability from a provider perspective and also from a payer perspective. Dr [Maia] Kayal, maybe you can define interchangeability for us. What are the requirements for the FDA? And what are the details of a switching study vs someone that doesn’t have that data? Is it a meaningful difference that we should be concerned about or would you treat more as a class effect?
Maia Kayal, MD, MS: That’s a great question. I think this is one of the most important points that we need to understand in the current trend of biosimilars. An interchangeable biosimilar can be substituted for the reference product without intervention by the prescribing health care provider. An interchangeable biosimilar isn’t necessarily safer or more efficacious than a traditional biosimilar. It just means that the manufacturer of the biosimilar took extra steps to prove to the FDA definitively that there was no clinically meaningful difference in safety and efficacy compared to the reference product. The way a manufacturer does this is through a switching study. A switching study essentially has 2 groups of patients. One group of patients starts on the reference product and remains on the reference product throughout the study. And then the other group that starts on the reference products may switch to a biosimilar, the one that is being studied to be interchangeable, and may switch back to the reference product. And then the outcomes of these 2 groups are compared. In a switching study that involves a biosimilar that’s being touted to be interchangeable, there has to be no clinically meaningful difference in terms of safety and efficacy between the 2 groups. That is the group that started on the reference then switched to an interchangeable then perhaps switched back or remained had the same exact efficacy and safety end points that the group that remained on the reference product had at the end of the study. This is important because, on a practical implication, this essentially means that whoever is administering the medication or sending it to the patients on the pharmacy level, if the FDA provides this interchangeable designation, then the pharmacist alone can choose to switch out the reference product for the biosimilar, the interchangeable biosimilar. Again, having that designation doesn’t necessarily mean that this biosimilar is better, more efficacious, or safer. It just means that the FDA had the data provided by the manufacturer through a switching study to prove definitively that there was no difference in the outcomes. So you do need to have that clinically meaningful, which would show that there is no clinically meaningful difference to get that designation.
Jonathan Kay, MD: But in the switching study, the primary end points are pharmacokinetic end points because the clinical end points that we use traditionally to study new drugs, especially in rheumatoid arthritis in which many of these drugs are studied, those end points can be superimposable for 2 completely different drugs. There was a study that was given the acronym AMPLE [NCT00929864] which compared adalimumab [Humira] to abatacept [Orencia] over 2 years in patients who had rheumatoid arthritis that was inadequately responsive to methotrexate. And all of the parameters, the American College of Rheumatology Response Criteria 20%, 50%, and 70%, also the change in the disease activity score using 28 joints, the change in health assessment questionnaire disability index, and the change in structural progression, all of those were superimposable at every time point over 2 years. So the clinical outcome measures that we use cannot detect differences in protein structure or mechanism of action as long as the medication is effective. So to demonstrate interchangeability with a difference between continuation on the reference product vs 3 back-and-forth switches from the reference product to the biosimilar and so on. Pharmacokinetic end points are necessary. And by doing so, these interchangeability studies demonstrate that approved biosimilars can safely and effectively be transitioned back-and-forth multiple times if necessary.
Transcript edited for clarity.
This activity is supported by an educational grant from Boehringer Ingelheim.