InterMune’s roller coaster ride with the idiopathic pulmonary fibrosis therapy pirfenidone took a steep dive back down when FDA issued a “complete response” letter asking for another clinical trial on May 4.
That decision, in one sense, is hardly surprising: FDA already made public the conclusion of its statistical reviewer that the NDA for pirfenidone didn’t meet the definition of “substantial evidence” for efficacy. Slam dunk non-approval.
Except that conclusion was presented to an FDA advisory committee in March for its consideration—with the remarkable outcome that many committee members seemed to agree that the data wasn’t sufficient to meet the “substantial evidence” standard, yet they voted for approval anyway.
It sure looked like a case where FDA was ready to be very flexible in the interest of making a potentially useful drug available for a horrific and untreated disease. One committee member actual voted “no” on the whether there was sufficient proof of efficacy, “no” on whether there was sufficient evidence of safety—and then “yes” on approvability. (Or, as we put it at the time, “No+No=Yes.”)
Apparently “substantial evidence” isn’t as flexible as all that. According to InterMune, FDA says it needs another trial to demonstrate sufficient evidence of efficacy. It may have to be a survival trial, or perhaps a trial with forced vital capacity as an endpoint.
InterMune says it won’t know for sure what will be required to support approval until after it meets with FDA to discuss the complete response letter. Still, the pivotal trial included in the NDA took three years from start to finish; replicating it means a prolonged delay.
So much for a “flexible” standard for substantial evidence, huh?
Maybe not. There is one wildcard in all this: pirfenidone is approved in Japan and marketed there by Shionogi. FDA wanted to review the Japanese trial data, but InterMune provided only summaries; the company didn’t think it would be worthwhile investing the time and resources to make individual case-level data available to the agency.
Our impression of the advisory committee was (and is) that the agency wanted the committee to, in effect, give them permission to approve pirfenidone based on something much less robust than you would expect for, say, a COPD therapy. FDA got that permission.
Still, it isn’t hard to understand why FDA would at least want that data before taking a chance on approving this application.
It may be that the “substantial evidence” standard still turns out to be more flexible than it appears to be—but with the caveat that, no matter how “substantial” it is, FDA expects to see all the data.
That decision, in one sense, is hardly surprising: FDA already made public the conclusion of its statistical reviewer that the NDA for pirfenidone didn’t meet the definition of “substantial evidence” for efficacy. Slam dunk non-approval.
Except that conclusion was presented to an FDA advisory committee in March for its consideration—with the remarkable outcome that many committee members seemed to agree that the data wasn’t sufficient to meet the “substantial evidence” standard, yet they voted for approval anyway.
It sure looked like a case where FDA was ready to be very flexible in the interest of making a potentially useful drug available for a horrific and untreated disease. One committee member actual voted “no” on the whether there was sufficient proof of efficacy, “no” on whether there was sufficient evidence of safety—and then “yes” on approvability. (Or, as we put it at the time, “No+No=Yes.”)
Apparently “substantial evidence” isn’t as flexible as all that. According to InterMune, FDA says it needs another trial to demonstrate sufficient evidence of efficacy. It may have to be a survival trial, or perhaps a trial with forced vital capacity as an endpoint.
InterMune says it won’t know for sure what will be required to support approval until after it meets with FDA to discuss the complete response letter. Still, the pivotal trial included in the NDA took three years from start to finish; replicating it means a prolonged delay.
So much for a “flexible” standard for substantial evidence, huh?
Maybe not. There is one wildcard in all this: pirfenidone is approved in Japan and marketed there by Shionogi. FDA wanted to review the Japanese trial data, but InterMune provided only summaries; the company didn’t think it would be worthwhile investing the time and resources to make individual case-level data available to the agency.
Our impression of the advisory committee was (and is) that the agency wanted the committee to, in effect, give them permission to approve pirfenidone based on something much less robust than you would expect for, say, a COPD therapy. FDA got that permission.
Still, it isn’t hard to understand why FDA would at least want that data before taking a chance on approving this application.
It may be that the “substantial evidence” standard still turns out to be more flexible than it appears to be—but with the caveat that, no matter how “substantial” it is, FDA expects to see all the data.
image from flickr user RubyJi used under a creative commons license
