By Asher Mullard
After years of speculation, consternation and excitement about the arrival of biosimilars in the United States, the competition is at last playing out.
In the past 2years, the FDA has approved four biosimilars. That number — although still far behind the more than 20 biosimilars approved to date by the European Medicines Agency (EMA) — could double by the end of the year (TABLE1). And, although biosimilar developers have only launched two of these biosimilars so far, US$17.5billion worth of biologic drug sales in the United States could be at risk of competition next year.
As importantly, the FDA has finally published most of the key guidance documents on the regulatory requirements for biosimilar development. The most recent, and one of the most significant, was the much-awaited mid-January draft guidance on interchangeability. Whereas a biosimilarity approval already allows biosimilar developers to market their drugs, an interchangeability designation enables pharmacists to switch a reference biologic product to a biosimilar without permission from the original prescriber (subject to state law) — a potential driver of biosimilar adoption, and profitability and sustainability of the sector.
"I’m quite impressed with the way that the FDA has dealt with this," says Cecil Nick, vice-president at Parexel, a clinical research organization that runs clinical trials for biologic and biosimilar developers.
The agency walked a tightrope, he says, and found a good balance between the statutory requirements as laid out in the Affordable Care Act, the science of biosimilar assessment and patient safety. "It could have been much worse," he says. "Now that the framework is in place, we expect we’ll see more interest in developing biosimilars for the US market," he says.
Regulation watch
The FDA had previously recommended that biosimilar developers follow a two-step pathway to market, first establishing biosimilarity to a reference product before seeking an interchangeability designation.
The 30‑page draft guidance explains what this second step involves. Although the agency will consider the totality of the data, the draft guidance also calls for clinical switching studies that assess the effects of alternating at least three times between the reference product and the biosimilar.
"We applaud the FDA in saying that more data are needed on switching," says David Charles, chairman of the Alliance for Patient Access, an advocacy group whose funders include biologics developers. As a physician, he says he is reluctant to recommend biosimilars to his patients in the absence of explicit clinical data proving that they function exactly as expected. He points in particular to a possible risk of increased immunogenicity reactions with switching.
His concern is exacerbated, he says, by the FDA’s willingness to extrapolate clinical data from one indication to another — allowing, for example, data from an efficacy and safety trial in an inflammatory indication to provide the basis for approval in an oncology indication. "Different patient populations may respond differently, and also may have different comorbidities," he says.
These arguments do not hold water for Gillian Woollett, senior vice‑president at Avalere Health, a consulting firm that supports biologic and biosimilar developers.
The biosimilarity analysis is designed to demonstrate that a product is biochemically and functionally equivalent to its reference, she says. And the agency is already well versed in such assessments, running comparability analyses for biologics every time a manufacturing change is introduced —
ensuring that a product has stayed ‘biosimilar' to itself over its entire lifetime. These analyses rarely require clinical data, she says.
In Europe, she also points o...
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