Biosimilar-to-Biosimilar Switching: What is the Rationale and Current Experience?

Abstract

Over time, clinicians have become increasingly comfortable embracing the prescription of biosimilars-highly similar versions of innovator or reference biological agents-for their patients with inflammatory diseases. Although a switch from a reference product to a licensed biosimilar version (or vice versa) is a medical decision robustly supported by the stepwise accumulation of clinical trial evidence concerning comparable safety, immunogenicity, and efficacy between these products, a switch from one biosimilar to another biosimilar of the same reference product, or a cross-switch, is not. Similarity among biosimilars of a reference product is not a regulatory agency concern and therefore is unlikely to be investigated in randomized controlled trials in the foreseeable future. Yet in clinical practice, across a diverse range of patients, the option to cross-switch from one biosimilar to another can and does arise for valid reasons such as convenience or tolerability issues, or driven by third parties (e.g., payers). In the absence of clinical trial data, clinicians must attempt to objectively evaluate the emerging real-world cross-switching evidence within the context of what is known about the science underpinning a designation of biosimilar. That knowledge then needs to be integrated with what clinicians know about their patients and their disease on a case-by-case basis. This review aims to consolidate relevant emerging real-world data and other key information about biosimilar-to-biosimilar cross-switching for prescribing clinicians. In the absence of clear clinical guidelines addressing this topic at present, this review may serve to facilitate discretionary and educated treatment decision making.

Interchangeability of Biosimilars: Overcoming the Final Hurdles

“…In 2019, Ebbers and Schellekens [9] argued that sufficient experience and data have been gathered regarding biosimilar evaluation and their use in clinical practice and called upon stakeholders to close the discussion on their interchangeability. In this issue of Drugs, Kurki et al [10] and Mysler et al [11] present two unique papers that address the topic of biosimilar interchangeability and provide important findings to inform and drive the debate to a conclusion. While both papers investigate the topic of interchangeable biosimilar use from different perspectives-regulatory and clinical-and do so through different approaches, they arrive at similar conclusions.…”

“…In this issue of Drugs , Kurki et al [ 10 ] and Mysler et al [ 11 ] present two unique papers that address the topic of biosimilar interchangeability and provide important findings to inform and drive the debate to a conclusion. While both papers investigate the topic of interchangeable biosimilar use from different perspectives—regulatory and clinical—and do so through different approaches, they arrive at similar conclusions.…”

“…While both papers investigate the topic of interchangeable biosimilar use from different perspectives—regulatory and clinical—and do so through different approaches, they arrive at similar conclusions. Kurki et al [ 10 ] provide insights from the EU regulatory perspective on interchangeability, and Mysler et al [ 11 ] focus on biosimilar-to-biosimilar switching from the clinical perspective. In this commentary, we discuss both papers, mainly from a European perspective.…”

“…In the second paper in this issue, Mysler et al [ 11 ] stress the importance of clinical decision making at the individual patient level, taking patient and disease variables into account on a case-by-case basis. While this may appear more challenging in a healthcare setting where substitution is introduced, the prescriber could annotate the prescription if necessary (e.g., “dispense as written”).…”

“…In the second paper we discuss in this commentary, Mysler et al [ 11 ] approached the question of the interchangeable use of biosimilars from a clinical perspective. The team of eight co-authors (notably, half are employed by Pfizer, an important player in both the originator biological and the biosimilar market) wrote an extensively documented review article, discussing virtually every angle related to the interchangeable use of biosimilars in clinical practice.…”