Signs of Change
Signs of progress are growing, especially in public sector institutions, such as the U.S. Department of Veteran’s Affairs system, that are negotiating prices and realizing significant cost savings by switching to biosimilars, Dr. Yazdany says.
In a recent study in Arthritis & Rheumatology, for example, researchers compared how the University of Pennsylvania Health System and the Philadelphia VA Medical Center prescribed biosimilar infliximab vs. its reference biologic, Remicade, from Jan. 1, 2015, through May 31, 2019.4
At the University of Pennsylvania, individual physicians chose what to prescribe, says Dr. Kay, the study’s senior author. Consequently, his team found only a small fraction of the health system’s doctors had begun switching over to the biosimilar by the end of 2018.
Through price negotiations, by contrast, the VA Medical Center saved 81% by choosing Renflexis (infliximab-abda), priced at $115.58 per 100 mg vial, vs. $623.48 for Remicade. Through a preferred designation in its national formulary, the VA has urged physicians to use the biosimilar except in special circumstances. By January 2018, the study found, doctors there were prescribing Renflexis or Inflectra (infliximab-dyyb) almost exclusively.
“When there’s a competitive bidding process, such as occurs in Scandinavian and other European countries, the competitive bids drive down the price of the biopharmaceutical,” Dr. Kay says. The biosimilar doesn’t always prevail; in Sweden, for example, the competition led to an 80% price reduction for Humira, which became that country’s adalimumab drug of choice. Whether the reference or biosimilar is selected under a winner-take-all system, “the healthcare system wins in any case,” Dr. Kay says.
Other U.S. insurers have used the competition to their advantage. In January, Massachusetts-based Health New England announced that it had saved $1.7 million through a prior authorization program launched Jan. 1, 2019, that prioritized use of biosimilar infliximab. Through the program, the nonprofit health plan said it had achieved a 93% utilization rate for the biosimilar.
Meanwhile, other studies are adding to the body of evidence that biosimilars closely match originator drugs in immunogenicity, safety and efficacy. Dr. Kay cites the
NOR-SWITCH study in Norway, which enrolled 482 stable rheumatology patients on Remicade (infliximab) and randomized them to blindly receive either Remicade or its biosimilar counterpart (now Inflectra, or infliximab-dyyb).5 After a year, the researchers calculated a non-inferiority margin of about 15%, based on the percentage of patients with worsening of disease activity, as assessed by a disease-specific index or a decision to change the treatment.
The study met its primary endpoint of a non-inferior clinical response in aggregate, but demonstrated non-inferiority for only one of the six individual diseases included in the trial. A far larger study would have been needed to have been powered adequately to detect such individual differences, Dr. Kay says. But as the only double-blind, controlled switching trial in a large group of patients, he says, the study was reassuring: “It showed that switching from Remicade to the biosimilar was not inferior to continuing Remicade over 52 weeks.” Likewise, an extension of the trial in which patients on Remicade were switched to the biosimilar for another 26 weeks showed they continued to do well.
Developers, such as Boehringer Ingelheim, maker of an adalimumab biosimilar, are likewise starting trials aimed at achieving “interchangeability” status by the FDA, which indicates a biosimilar yields identical clinical results to its originator counterpart.
Gaining interchangeability status requires extra data about the risk of alternating between drugs or of switching from one to another. With the designation, a pharmacist could theoretically substitute the interchangeable biosimilar for its reference product without the prescribing physician’s authorization, as is the case in some European countries. Preemptive legislation in 32 U.S. states, however, requires notification of both the patient and the provider.6
Guidance from the FDA on interchangeability trials finalized in May 2019 “could potentially have a significant impact on the uptake of biosimilars,” Dr. Yazdany says.
