Despite Financial Incentives, Greater Understanding Is Needed to Back Biosimilar Use


Sandra Cuellar, PharmD, BCOP, discusses the benefits of using biosimilars in oncology, the approval process for these agents, and the reasons why biosimilars have been met with reluctance in the medical community.

Sandra Cuellar, PharmD, BCOP

Sandra Cuellar, PharmD, BCOP, oncology resident director, clinical pharmacist, team leader of Ambulatory Pharmacy Services, and clinical assistant professor of Pharmacy Practice in the College of Pharmacy at the University of Illinois

Sandra Cuellar, PharmD, BCOP

Despite some reluctance regarding the use of biosimilars, which stems from a lack of understanding of the development and approval process, the role of biosimilars in oncology continues to expand, said Sandra Cuellar, PharmD, BCOP.

Moreover, these agents' cost-savings potential is a driving incentive for their use in the field, she added.

There are currently 5 FDA-approved biosimilars for trastuzumab (Herceptin), including ABP 980 (Kanjinti; trastuzumab-anns), PF-05280014 (Trazimera; trastuzumab-qyyp), CT-P6 (Herzuma; trastuzumab-pkrb), SB3 (Ontruzant; trastuzumab-dttb), and MYL-1401O (Ogivri; trastuzumab-dkst).

On March 24, 2020, a 420-mg multidose vial of trastuzumab-dttb was approved by the FDA for the treatment of patients with HER2-overexpressing breast cancer or metastatic gastric or gastroesophageal junction adenocarcinoma.

Although there are multiple biosimilars and no head-to-head comparative data, treatment selection is largely driven by payers, explained Cuellar. The main challenge is understanding the extrapolation of clinical data for multiple biosimilar indications, said Cuellar.

"The question of which biosimilar to select is surfacing more often now [in breast cancer]," said Cuellar. "Each agent was approved based on the totality of evidence that is critical to scientifically justify extrapolating [the data for use] in other indications. Moreover, each biosimilar has gone through the rigorous analytical characterization compared with the reference product. I feel comfortable saying that any of these biosimilars are acceptable [for use in the clinic]."

In an interview with OncLive, Cuellar, oncology resident director, clinical pharmacist, team leader of Ambulatory Pharmacy Services, and clinical assistant professor of Pharmacy Practice in the College of Pharmacy at the University of Illinois, discussed the benefits of using biosimilars in oncology, the approval process for these agents, and the reasons why biosimilars have been met with reluctance in the medical community.

OncLive: What are the advantages of using biosimilars?

Cuellar: The benefits of utilizing biosimilars come primarily from a pharmacoeconomic standpoint. These drugs represent a mechanism in which we can contain cost and increase access to [treatment] without compromising quality, efficacy, or safety. That is the primary driver of why we are using these agents.

Historical perspectives have shown that the price [patients] used to pay for biologics 10 years ago has increased 80% because there is no market competition. In 2009, legislation was passed by Congress allowing biosimilars to enter the market, and allowing us to provide these drugs to our patients while controlling cost.

Could you shed light on the biosimilars that are approved in breast cancer?

Currently, 5 trastuzumab biosimilars are approved by the FDA in essentially the same setting. We cannot say that 1 of these biosimilars is better than another because there have not been head-to-head comparative trials. The trials that have been conducted have been noninferiority or equivalence studies.

Are biosimilars distinguishable?

From an institutional perspective, we look at the efficacy, safety, and clinical trial design. Although they are all FDA approved, there are nuances and differences between them. For example, some studies were done in the neoadjuvant setting looking at pathologic complete response rates. Other studies looked at these agents in the metastatic setting. They are both considered sensitive and appropriate [settings] to test these biosimilars in, but they are different. They have different endpoints.

What role do payers play in determining whether a patient receives a biosimilar?

In looking at which agent we should select in practice, everybody has different ways of approaching that decision. First, it is going to come down to the payers. The payers have more of a prescriptive [say] in which biosimilars to use. That could be an arrangement with the payer and the pharmacy benefit managers, or the payer and the manufacturing company.

In other models, such as what we have seen at our institution, commercial payers are asking us to consider using a particular biosimilar, but they are not making it mandatory yet. Some payers are saying that they will give the approval for the reference product, but at that point of authorization, they request that we consider a biosimilar. The payers will reimburse these biosimilars at different rates.

We also look at the pharmaceutical manufacturing company, where the agent is being manufactured, accessibility, and dependability. There is some confidence associated with some of the pharmaceutical companies that have a long history of making biologics; that can provide a bit more comfort to us as well.

Ultimately, it boils down to the numbers and how those numbers play out at an individual institution with the payer.

What other challenges remain in this space?

Part of the existing challenge is that a knowledge gap still exists in terms of how the biosimilar data package is approved compared with the reference product. [This particularly applies to] how the abbreviated data package is submitted to the FDA and subsequently approved, and extrapolated [for use in other tumor types].

For example, an agent that has been studied in lung cancer is now approved in colon cancer, but there are no data specifically in colon cancer. It is a paradigm shift of what we are used to. We are used to seeing the biologic being studied in each individual indication, so that we have individual data. The concept of extrapolation can cause some hesitancy among health care professionals.

Could you discuss the approval process for a biosimilar?

The predecessor to this whole process is [that of] generic drugs. In 1984, legislation passed stating that generic drugs could be approved without having to go through the same clinical trials that the originator, small molecule-branded drugs did.

For example, when atorvastatin (Lipitor) was approved, it was based on phase 3 clinical trials. Generic atorvastatin did not have to produce those studies. As a health care community, we felt comfortable knowing that the generic was identical to the brand name drug and, therefore, we didn't feel there was a need to conduct those clinical trials.

When we transition over to biologics, the premise is similar in the sense that the FDA and manufacturers are doing rigorous analytical characterization [of the biosimilar]. However, the difference is that [a biosimilar] is a more complicated biologic product. Inherently, you cannot have a biologic and biosimilar be identical to each other. The challenge is in understanding that these biologic agents are never going to be identical, but the analytical characterization and testing of these biosimilars, should be as similar as possible.

While the FDA does not use this language anymore, the process [can be related to] a fingerprint in terms of similarity. Critical attributes that are identified in a biologic agent are also present in the biosimilar, [therefore] they are the same.

There is minimal uncertainty that if we were to put these biosimilars in a clinical trial that they would behave any differently [than the biologic]. They act similarly in pharmacokinetic/pharmacodynamic modeling, and they have the same pharmaco-elimination, area under the curve, molecular weight, and structure [compared with the biologic].

Clinical trials would confirm what we already know, but the extrapolation concept is difficult. We are not all basic scientists, and we are used to getting data from big clinical trials rather than analytic data of critical molecular attributes. Understanding this concept though is where the cost of developing these biosimilars comes into play.

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