2019: The Year that Interchangeability Might Change the Biosimilars Landscape

George C. Yu, JD, is a partner in the Intellectual Property group of Schiff Hardin LLP. He is an experienced patent attorney who focuses his practice focuses on patent infringement litigation and counseling and has worked in private practice and in-house positions. George has litigated patents relating to recombinant proteins, monoclonal antibodies, microarray technology, and small molecule therapeutics. George has advised companies developing novel biologics as well as biosimilars on patent strategy.
  Christopher Bruno, JD, is an associate in the Intellectual Property group at Schiff Hardin LLP, and a former law clerk of the United States Court of Appeals for the Federal Circuit and of the United States District Court for the Central District of California. With a focus on pharmaceutical product patent litigation, he has litigated Hatch-Waxman cases from pre-complaint investigation through appeal in district courts, the Federal Circuit, the Supreme Court, and the International Trade Commission. Chris was one of the first attorneys with experience litigating the meaning of provisions of the Biologics Price Competition and Innovation Act of 2009, and continues to play a role in decoding the relatively nascent territory of biosimilar litigation.
February 12, 2019
This year, the biosimilar landscape will likely focus on interchangeability as biosimilars manufacturers and other stakeholders seek to reduce costs and increase uptake. This follows the 2018 trend of biosimilar litigation settlements and the attention in 2017 to the information exchanges, also known as the “patent dance,” laid out in the Biologics Price Competition and Innovation Act of 2009.

So why does a biosimilar company want its product deemed interchangeable? The designation allows a pharmacy to substitute the interchangeable biologic product for the reference product without the prescriber’s intervention, just as generic drugs can be substituted for a branded product. Many argue that interchangeability is a key to reducing the prices of biologic treatment because, until now, commercial factors have led to small market share for on-the-market biosimilars.

What might change this year, and how will industry react?
At the J.P. Morgan Healthcare Conference earlier this year, and consistent with the July 2018 Biosimilar Action Plan, FDA Commissioner Scott Gottlieb, MD, signaled that a finalized interchangeability guidance and a structured application for seeking interchangeability would be forthcoming shortly. The hope among biosimilar companies is that the guidance will streamline the regulatory pathway and create well-defined scientific criteria. But even if the first interchangeable product satisfies FDA’s requirements, that could be the beginning of a long and expensive legal road. Reference product manufacturers will likely file citizen petitions challenging the designation and possibly litigate interchangeability with court challenges as well. Competing biosimilars manufacturers may attack one another as well, as the recent filing of Coherus v Amgen—a patent litigation between 2 biosimilar companies over adalimumab—demonstrates (see a summary of the lawsuit here).

Additionally, there will likely be a focus on facilitating faster adoption of interchangeable drugs through automatic substitution requirements, whether instituted by changing government payer plans or enacting new legislation. Existing state law varies in permissiveness toward interchangeable biosimilar substitution (a 50-state survey is available here), including whether substitutions are mandatory.

Background on interchangeability and its importance
In order for a biological product to be approved as a biosimilar of a reference product, it must be highly similar and have no clinically meaningful differences from a reference product—ie, it must be structurally similar and be as safe and effective as the reference biologic drug. The drug can still have minor differences in clinically inactive components and still be approved as a biosimilar.

The standard of evidence for an interchangeable product is higher. All the conditions of biosimilarity apply, but an interchangeable biosimilar product must also be shown to “produce the same clinical result as the reference product in any given patient.” Additionally, a biologic drug that requires multiple administrations for treatment can be deemed interchangeable only if the data show that there is no increased safety risk or decreased efficacy from switching between the reference biologic and the biosimilar product.

To produce this data, biosimilar applicants must spend significant resources to conduct clinical trials to satisfy these requirements (for example, Boehringer Ingelheim's interchangeability study comparing BI 695501, Cyltezo, to Humira). By contrast, in the European Union, there is general agreement that switching studies are unnecessary to guarantee safety, and that real-world experience has not shown a high risk of adverse events (see further context about the EU perspective here).

That comfort relies in part on NOR-SWITCH, a Norwegian government-sponsored switching study comparing CT-P13 (Inflectra, Remsima) with Remicade, which found that switching to biosimilar infliximab rather than continuing Remicade had no negative impact on patients’ treatment.

The FDA, at least to date, has not yet provided certainty about how to show interchangeability. Though the agency released a draft guidance in January 2017, the guidance still has not been finalized, to the dismay of insurers, medical providers, and biosimilar industry groups who authored an August 23, 2018 letter to the FDA on the matter. And because no biosimilar products approved for marketing have yet been designated as interchangeable, biosimilar companies looking to establish interchangeability do not have a model to replicate.

It will be interesting to see whether the FDA’s prediction of the marketing of an interchangeable biosimilar in 2019 will hold, and if so, what additional legal challenges await.

 

x-button

Health economics experts. Managed care professionals. Key clinical specialists. This is where the worlds of clinical, regulatory, and economical outcomes for specialized pharmaceutical biotechnology meet: The Center for Biosimilars is your online resource for emerging technologies, with a focus on improving critical thinking in the field to impact patient outcomes. We’ll discuss the current landscape for advanced health care management—reviewing emerging treatment paradigms, approaches, and considerations—all by authoritative industry voices.

Intellisphere, LLC
2 Clarke Drive
Suite 100
Cranbury, NJ 08512
P: 609-716-7777
F: 609-716-4747
Copyright © 2006-2019 Intellisphere, LLC. All Rights Reserved.