To feel comfortable with generic biologics (biosimilars), US payers are likely to require more clinical information than what might be accepted by the Food and Drug Administration (FDA) for approvals, a new report suggests.
For example, FDA approval of biosimilar versions of monoclonal antibodies (MAbs) for oncology indications will not allay all the concerns felt by the majority of payers about bioequivalence, says the report, from research firm Decision Resources.
US payers questioned for the study also indicate that six to 12 months' clinical trial duration would be insufficient to convince them that a biosimilar has equivalent efficacy and safety to the originator biologic for MAbs or fusion proteins.
"Because MAbs are highly complex biologics compared with more simple proteins, FDA approval will only go part way in satisfying payers' doubts over these more elaborate agents," says Andrew Merron, biosimilars advisory service director at Decision Resources.
"Overall, biosimilar manufacturers developing biosmilar MAbs will need to invest in trials lasting at least one year to convince the majority of payers about bioequivalence," he advises.
The study also finds that both US and European payers identify tumour necrosis factor (TNF)-alpha inhibitors as their top priority for reducing biologic spend.
"TNF-alpha inhibitors represent a major cost burden to payers, so this class of biologic may receive greater pressure to prescribe biosimilars compared with other biologic classes," Dr Merron forecasts.
Meantime, providing the first insights into how the FDA plans to tackle approving biosimilars, a group of leading agency regulators says that this is unlikely to include a 'one size fits all' systematic assessment.
Writing in the New England Journal of Medicine (NEJM, August 4 issue), the regulators - who include Dr Janet Woodcock, director of the FDA Center for Drug Evaluation and Research (CDER) - say that reconciling the science of biosimilar development with the new "abbreviated" regulatory approval framework required under the Biologics Price Competition and Innovation Act (BPCI), passed by Congress in 2009, presents the FDA with "numerous" challenges.
First and foremost, they say, the agency must establish scientific criteria that address the key question: "how similar is similar enough when it comes to the substitution of complex biologic drug products in clinical practice?"
Fortunately, progress in the characterisation and understanding of biologics now permits demonstration that some products are highly similar to a reference product, and the FDA's experience with biologics provides important relevant knowledge, the regulators write. Moreover, they add, the agency is "carefully scrutinising" lessons from the European Medicines Agency (EMA), which published general guidelines on biosimilars in 2005 and approved its first such product in 2006.
Initial EMA guidance has suggested product-specific requirements for structural, animal and clinical studies, they say, adding: "given the complex nature of biologics, it is unlikely that a 'one size fits all' systematic assessment of biosimilarity can be developed."
The FDA's traditional "totality of the evidence" approach can also be applied to assessing biosimilars, but the new pathway will require "a new paradigm for sponsor-FDA interactions," the regulators note.
"Although the agency frequently meets with sponsors before they submit Investigational New Drug Applications, a more extensive product review will be required to determine how much additional data are needed for a biosimilar. The FDA is currently considering how such interactions might be structured and how they will affect the user-fee programme that Congress has mandated for biosmilars," they write.