These difficulties, she said, may make it hard to create a low-cost version of these types of biologic agents.
European Versus U.S. Process
Europe, however, recognizes that biosimilar agents are possible, said Dr. Laslop, who added, “We anticipate future approval [even] of biosimilar monoclonal antibodies.”
A draft EMA guideline on biosimilar monoclonal antibodies, according to Dr. Laslop, would require drug makers to establish that a biosimilar is equivalent to the reference product, although the agency is discussing a noninferiority approach.
Under its 2005 general guidelines on biosimilars, the EMA requires a biosimilar development program to establish biosimilarity to a reference drug, not to establish treatment benefit for the individual patient. Therefore, it may waive efficacy studies. For clinical comparability studies of biosimilar monoclonal antibodies, the EMA prefers to see an endpoint based on treatment response, said Dr. Laslop.
She acknowledged that it is becoming more challenging to rate the clinical relevance of small differences in quality. The EMA is revising its current guidelines to address changes in manufacturing during a product’s life cycle.
“For clinical comparability, it is about choosing the most sensitive and homogeneous population, which may be healthy volunteers or patients,” Dr. Laslop said.
However, Dr. Strand said, “In rheumatology, we don’t typically have homogeneous populations, or necessarily ones we can identify as most responsive to a given therapeutic agent.” Dr. Strand also stated that the FDA most likely will not use noninferiority to compare a biosimilar to a reference product.
“We’re not going to be able to say a biosimilar is noninferior, because that would allow a broader definition of equivalence,” Dr. Strand said. “Unfortunately, ‘biobetter’ won’t happen because the FDA defines a biosimilar as clinically equivalent and substitutable.”
How Close Are We?
The challenges of creating biosimilar products rise with the increasing complexity of the biologic product. For peptides and short proteins, it may even be possible to create bioidentical products, according to Dr. Laslop.
“For more complex and variable molecules such as large blood-derived products and so-called advanced therapy medicinal products, the question is whether they can ever be biosimilar,” Dr. Laslop said. “Currently we are still far away from that.”
The take-home message of this symposium, Dr. Ruderman told The Rheumatologist, is: “Biosimilar drugs are coming to the United States, but there are a large number of challenges before we can get to that point.”
Disclosures
Dr. Felix is an employee and stockholder of Amgen. Dr. Strand discloses that she is a consultant to Abbott, Alder, Amgen, Anthera, AstraZeneca, Biogen Idec, Biotest, BMS, Centocor, Genentech, GSK, Human Genome Sciences, Incyte, Lilly, Medimmune, Millenium, Merck-Serono, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche, Sanofi Aventis, Savient, and UCB. Dr. Laslop and Dr. Ruderman report no financial conflicts of interest.
