The three described accelerated approval as "a medium-term stopover en route to full approval or market withdrawal."
If the FDA lacks a genuine ability to withdraw accelerated approval due to inadequate or unfavorable data from confirmatory trials, the regulator would have few tools to ensure that companies provide the new data they promised in exchange for accelerated approval, they said. "Although such adverse decisions may be contested, the integrity of the accelerated approval process and the FDA’s reputation and authority as a public health agency require that it be willing to make and adhere to these difficult decisions."
In its written summary of the evidence it intends to present at the hearing, Genentech argued that CDER’s withdrawal decision rests upon a new standard – one requiring either an overall survival benefit or PFS of an unspecified magnitude – that may deter development of new treatments for MBC.
However, Dr. Carpenter and his colleagues found this argument unpersuasive.
"The FDA often removes indications from labeling and commonly rejects new drug applications. Yet there is no consistent evidence that such actions deter the development of clinically valuable therapies," they said. "Indeed, the relationship might be the reverse: if bevacizumab offers little promise for patients with metastatic breast cancer, then removing the indication may create a clinical and market niche that provides other companies with an incentive to develop a better product for, or test available products in, that population."
The credibility of both the agency and the accelerated approval process hangs in the balance, the Harvard professors asserted.
"Underlying the back-and-forth about bevacizumab’s trial performance is a larger issue: the precedent that will be established if the FDA reverses its decision on withdrawing bevacizumab’s labeling for metastatic breast cancer not because of changing scientific evidence, but in response to philosophical and political counterarguments," they wrote.
"If the FDA demonstrates that it is unable or unwilling to withdraw accelerated approval when the totality of evidence fails to meets its standard for regular approval ... such a precedent risks undermining the basis for accelerated approval mechanisms and, more broadly, the agency’s credibility as it seeks to regulate medical products for the public good."
CDER similarly has warned that it must be able to withdraw approval when confirmatory trials fail to verify clinical benefit or else the accelerated approval process will operate as a lower standard.
This coverage is provided courtesy of "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.