ASHP Midyear: Pharmacists Play Key Role in Addressing Concerns and Fostering Adoption of Biosimilars
Amanuel Kehasse, PharmD, PhD, director of clinical programs and drug information at Clearway Health, discusses the crucial role pharmacists can play in adapting biosimilars into clinical practice. Biosimilars face significant regulatory and market hurdles, from the complex development process to patent litigation and exclusivity challenges. Even after overcoming these hurdles, physicians and patients often express concerns about biosimilars due to a lack of knowledge about their approval, extrapolation of indications, and potential immunogenicity. As drug experts positioned between patients and providers, pharmacists can develop continued medical education programs to foster a better understanding of biosimilar concepts.
Pharmacy Times: What are the key regulatory hurdles for biosimilar development and approval, both domestically and internationally?
Amanuel Kehasse: So, there are several regulatory hurdles that a biosimilar has to undergo, starting from their development, to bringing them to [the] market, and successfully launching them in the market. And it starts with the very development process, biosimilars are complex molecules and they have to be highly similar to the reference product in terms of their primary structure, post-translational modification, and then their function in safety and efficacy. So, they are asked to generate a lot of data to demonstrate that one and the complexity is really, really huge, and I can actually demonstrate [with a] simple example using a generic versus a biosimilar development process. When you are developing a generic product of small molecule[s], it is relatively easier to replicate [the] exact molecule of the reference products through a predictable chemical synthesis process; however, biologics—which are biosimilars as well—are complex molecules that are produced inside a living organism, so it's virtually impossible to create an exact replica of the reference product. So, there is going to be an inherent slight difference in terms of their post-translational modification, which is decorating the amino acid sequences. But these differences should not result in any clinically meaningful safety, efficacy, or immunogenicity differences. To demonstrate all these things, they are asked to generate tons of data, so this is 1 hurdle in comparison to generics. And then, when it comes to clinical trials, unlike generics, biosimilars actually have to undergo clinical trials to demonstrate their safety, efficacy, and immunogenicity, this is an additional hurdle for biosimilars that you don't see in generic products. After you've gone through all these hoops and actually developed a biosimilar product, before they hit the market, there is this hurdle we call patent litigation and exclusivity of the reference product. So, a lot of biosimilars have been kept out of the market simply because of the patent litigations. Some of the manufacturers did not go through the lengthy patent litigation process, so they agreed for the pay to delay with the reference product manufacturer, [and] their product will be sitting for years until we see the market. All these hurdles are really, really making...developing biosimilars and bringing [them to] the market [a] really complex process.
Pharmacy Times: How can pharmacists address misconceptions and concerns among health care providers and patients about biosimilar safety and efficacy?
Kehasse: That's actually important because once you get through all these hurdles to bring this biosimilar into the market, the key piece of the puzzle is, how do you adapt this one into clinical practice? And that has to do with patients, [health care] providers, and other stakeholders as well. And we know from existing data, physicians and patients have concerns about biosimilars, and these concerns could be [because of] lack of or maybe [a] gap in knowledge about the biosimilar concepts, how they're developed, the extrapolation of indication, the immunogenicity...As you know, biosimilars do not have to go clinical trial for every indication that they have to get approval for. If you're able to demonstrate safety, efficacy, and immunogenicity in 1 representative disease state, then the biosimilar can have actually indications for multiple disease states that their first product has. So, a lot of providers have this concern [of] you haven't tested this drug in all these disease states, how can I prescribe? There is a lot of hesitancy that came from lack of knowledge on the process itself, so pharmacists, as drug experts...we are in between the patient and the physician, we can play a significant role in terms of like developing continued medical education to foster the knowledge base about biosimilar concept, how they are approved, why the extrapolation indication is not a significant issue, or the interchangeability of biosimilars. We can hammer on all these things and make sure that the patients are comfortable and physicians are comfortable to adopt biosimilars. If we don't do that, patients will be resistant, and if you actually force it through insurance requirement or other regulatory requirement to transition to biosimilars, then they will have this nocebo effect, which means they have this perception that this biosimilar is inferior to the reference product, they will have a disease manifestation, then will [be] forced to switch back to another biosimilar or reference, which impacts the patient experience. Education is the key piece to make sure that we address all these things. Also, considering patient concerns and values is also important, because if we always are making decisions for the patient without involving them in the decision-making process, that's another part that we need to make sure to address. Patients have to participate in the decision-making process, they will feel comfortable about the decision made on their care.