Because biosimilars piggyback on much of the clinical work already done on the drugs they imitate, they can be brought to market for less money, and therein lies the savings potential for patients and health systems, according to Lee S. Schwartzberg, MD.
Biosimilars can produce savings because their approval process requires fewer costly clinical trials than their reference biologics, Lee S. Schwartzberg, MD, explained in an interview.
“To be honest, that’s really the whole benefit of biosimilars, that the expensive part of the process, which is doing these large clinical trials, doesn’t have to be done if you have a product that looks highly similar with only minor differences,” Schwartzberg noted.
Schwartzberg, an expert in the treatment of breast cancer, precision medicine, and supportive care, is the chief medical director of the West Cancer Center and chief of hematology and oncology at the University of Tennessee Health Science Center, both in Memphis. He also is a member of the board of directors of the National Comprehensive Cancer Network.
Although a biosimilar must be as safe and effective as the reference product, biosimilar trials that qualify for FDA approval need only be equivalence trials, which demonstrate safety, purity, potency, and similarity to the originator.
“For a biosimilar…it’s a true pyramid, where most of the work is done showing that the analytic purity and similarity to the originator is identical, and less work for the clinical process, because if you show that the biosimilar is, in fact, highly similar to the originator product in terms of the way it looks—the product itself, its functional attributes, its pharmacology, and its pharmacokinetics—then you can do fewer clinical trials,” Schwartzberg said.
The FDA approval process for a biologic is lengthier, requiring phase 1, phase 2, and potentially multiple phase 3 trials. The number of subjects and the criteria governing who may be enrolled on a study increase with each phase, Schwartzberg said. Such trial processes are unnecessary for the approval of a biosimilar.
However, biosimilars do face rigorous quality assurance tests that look at the way the drug is being manufactured and the analytic variables that show similarity to the originator product. Analytic and functional attributes must be highly similar to the originator, Schwartzberg said.
Ultimately, in-human pharmacokinetic and pharmacodynamic studies are done to demonstrate “that the drug is handled in a person’s body and a patient’s body the same way that the originator is.” These will be followed by, generally, a single large-scale clinical trial to demonstrate that efficacy and safety are equivalent or noninferior to the reference product, he said.
“Statistically you have to show within a narrow range that the outcome is very similar between the biosimilar and the originator product. But the key difference is you’re doing only 1 large trial, and that suffices for the FDA to approve the drug to be used for the biosimilar the same way the originator is used,” he said.
Schwartzberg defined a biologic as a medicine made in a living cell and a biosimilar as a highly similar version of the originator biologic. Examples of both include antibodies, antibody drug conjugates, and other things made in living cells with complex molecular structure.
Owing to the intricate biological product manufacturing process—they are made from living organisms—biosimilars can vary from batch to batch. Even batches of the reference product may not be perfectly identical, Schwartzberg said.
Biologics differ from small molecule drugs in that small molecule drugs are made through chemical processes that are easy to replicate. Biosimilars differ from generics in that generics are exact copies of their reference products, with no variations between batches.
The FDA began approving biosimilars in 2015 when it gave marketing clearance for Zarxio, a filgrastim biosimilar.
The uptake of biosimilars in the United States is impeded by multiple factors, including medical reimbursement policies and the patent protections for dominant brands. Europe is generally considered to be about 10 to 12 years ahead of the United States in biosimilar approvals and launches.