According to guidance published by the US Food and Drug Administration (FDA), a biosimilar developer can “extrapolate clinical data intended to support a demonstration of biosimilarity in one condition of use to support licensure of the proposed biosimilar product in one or more additional conditions of use for which the reference product is licensed.”
Applicant's must “provide sufficient scientific justification for extrapolating clinical data,” as was the case in the one US example we have - Sandoz’s Zarxio which was granted approval throughout Amgen’s indications for Neupogen last March.
“This practice is consistent with other decisions by FDA, including not requiring human immunogenicity data on ethical grounds, that have as a consequence - if not a goal- reducing the time to approval and burden on the biosimilar applicant,” said Kevin Noonan, a Partner at McDonnell Boehnen Hulbert & Berghoff, LLP.
Noonan, an experienced biopharma patent lawyer, told Biopharma-Reporter it is “possible to take this ‘shortcut,’ at least for now, because many of the biosimilar drugs now seeking approval in the US have been approved in Europe.
“Thus, there is not only clinical trial data but also actual clinical data from live patients supporting the practice.”
Next Generation Biologics and biosimilars
So long as a biosimilar proves biosimilarity on analytical grounds and the existence of pharmacodynamics and bioequivalence data for at least one (presumably the predominant) indication, the risks of extrapolating data across indications are likely to be minimal, he said.
But the problem lies with untested copycat products and the next generation of monoclonal antibody (mAb) biosimilars beginning to target the market.
“While the FDA has been cautious in general regarding the biosimilars pathway, the agency may be thinking that the European experience with this first class of drugs is something of a safety net for testing whether there may be sufficient danger or uncertainty that clinical trials for all indications are necessary, desirable or prudent.”
Noonan continued: “The lessons learned from the current crop of biosimilars may not be so directly applicable to new biologic drugs, and the severity of any problems that arise will influence - if not determine - whether this practice will continue.”
Government, payer and drugmaker jeopardy
And furthermore, he warned, if any significant morbidity or mortality becomes associated with a product, there could be serious repercussions for the whole biosimilar sector.
“This would be bad for the government, which has a vested interest in patients and physicians accepting biosimilar substitution to reduce drug costs, and for insurers and others who are bearing the costs of relatively higher priced biologic drugs.
“In addition, there have been cases recently decided by the Supreme Court to the effect that FDA approval does not prevent injured patients or their families from suing drug companies under strict liability tort claims.”