I wonder how the new FDA quidelines might affect Sorrento's cancer portfolio?
FDA spells out how cancer drug developers can use one trial for both accelerated and full approvals
Zachary Brennan, Senior Editor Endpoints
"The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.
While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.
OCE officials discussed this concept of a single trial in the NEJM last October, explaining: “AA could be granted on the basis of a planned interim analysis of overall response rate, and traditional approval granted on the basis of clinical benefit (usually improvement in overall survival) at the trial’s conclusion.”
But the design of that trial must be precise as FDA says in today’s draft guidance that it must be “powered for the longer-term clinical endpoint with follow-up in the same trial to verify clinical benefit,” and should ensure that the accelerated nod doesn’t inadvertently introduce bias.
So what are the benefits of such an approach? FDA points to “a more thorough safety assessment and earlier definitive evidence of the benefit–risk balance,” as well as reducing the risk of halting the drug’s development too early, or one with a limited overall response rate that may end up as an OS improvement. Moreover, the randomized trial could be conducted in patients in an earlier treatment setting, the draft adds, so the drug would reach more patients in whom efficacy might be greater.
As far as logistics, the draft notes, “The trial sample size should be chosen so that it has adequate power to detect a clinically meaningful and statistically significant improvement in both the endpoints for accelerated approval (e.g., response rate) and verification of clinical benefit (e.g., PFS or OS).”
Because the treatment landscape for cancer is constantly in flux, FDA explains that sponsors should discuss any updates with the agency, which could lead to deferred accelerated submissions until the results for a traditional approval are available. That may be a sticking point for industry, which if they run one trial and a confirmatory follow-up, can make money on the AA while the follow-up trial is ongoing.
FDA also makes clear, as with the passage of the omnibus at the end of last year stipulated, that the agency may “require, as appropriate, that studies intended to verify clinical benefit be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.”
Such confirmatory trials must be carried out with “due diligence,” the agency notes, as the OCE officials previously explained in the NEJM how the median time for oncology accelerated approvals to either confirm benefit or fail was longer if the confirmatory trial was initiated after the approval. The guidance also does not discuss the expedited ways in which FDA can pull AAs if they fail those confirmatory trials, which was also included in the omnibus."
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