FDA's Jenkins: Our Standards Haven't Changed

John Jenkins is the FDA's director in the Office of New Drugs, and a 16-year agency veteran which means he is constantly in the thick of it. And so

The RPM Report, which does a marvelous job tracking the agency and its interaction with pharma, sat down to quiz Jenkins on the latest hot button topics. The following is an excerpt (and for those who would like to read more, follow this asterik* below for instructions).

RPM: With new molecular entity approvals at the lowest number since 1983 and the drug industry spending about 11 times more on R&D than it did 25 years ago, can you comment on what you think the problems are in getting new therapies approved?

Jenkins: We’ve been analyzing these data internally. One thing that struck me is that if you exclude the peak that occurred in 1996 and then a shoulder peak in 1997 for NME approvals, the curve is much flatter than the dramatic fall that we’re all concerned about. Everyone is concerned that in ‘96 and ‘97, we had this peak of about 50 NMEs approved and it’s been downhill ever since. If you flatten out those two aberrant years, the curve is much flatter and looks much less dramatic. One thing we want to further analyze is whether ‘96 and ‘97 might be aberrant years because that may simply have reflected clearing out things backed up before (the reauthorization of the Prescription Drug User Fee Act). We haven’t done that analysis yet. That ‘96 peak may be a false data point.

RPM: You have headed up the Office of New Drugs for almost six years now. Are there approval decisions made today that would have been different if they were made when you started the job?

Jenkins: I don’t think it’s really possible to know the answer to that question. It’s hard to take an application that’s being reviewed in 2008 and try to think what would we have done with this application in 2002. I do feel comfortable in saying that the statutory standards have not changed. We have never - I’ve actually been here 16 years, six years in the current job - systematically issued a directive to our staff that we should slow down or speed up on approvals. I don’t think the standards have changed, but in some cases the science changes. It becomes a hard question of how do you apply the evolving science. We didn’t know as much in 2002 about some of these drug classes as we know today.

There’s no doubt that the climate today that we’re operating in as far as the public scrutiny, investigations, criticism is much more intense than it was in 2002. How much impact that actually has on day-to-day decision-making on applications is very hard to quantitate. We have to recognize that the people in my office that make these decisions are making them based on a judgment of the benefit and risk of the drug. Is it possible that their judgment of a close case is being influenced by the current climate? That’s possible, but we don’t see any data that yet support that it’s actually happening.

RPM: If you could address a room full of biopharma CEOs, what would you say are some of the most important things they could be doing to improve drug development? And what things should they not be doing?

Jenkins: There’s a lot of things that someone could point to...

...Something that struck me was the frequency of which the issues that we still find to be deficiencies when we send an action letter, how often (those deficiencies) were identified as early as the end-of-Phase II meetings but were never addressed to our satisfaction. That I found to be a pretty stunning finding (of a Booz Allen report on NME reviews). Despite our investing a lot of time and energy in meeting with companies and sharing that information, it was still an outstanding issue by the time - not only when the application was submitted - but when it was up for its PDUFA goal date.

RPM: It’s clear from the Booz Allen report (on NME reviews) that small companies had a much tougher time with first-cycle review rates?

Jenkins: Clearly I think there’s a factor in there of inexperience and lack of regulatory savvy, but also maybe they get too invested or too wedded to their product and can’t see the forest by being buried in the application. We do see cases where it’s so clear to us “this isn’t going to get approved.” But the application gets submitted.

We even had one last year where we refused to file it (Pharmacyclics lung cancer drug, Xycitrin). It was filed over protest and we still issued the “non-approvable” letter. We had to review it, which we didn’t think was a good use of our resources, but they still got a “non-approvable” letter. I don’t really understand that psychology. I don’t know if that’s a business strategy to keep the investment community funneling money into the company or if that is a true belief that this drug works and that they will be able to convince us that they’re right and we’re wrong. I don’t really understand it.

RPM: What is the working relationship like between the Office of New Drugs and the drug safety group now (the Office of Surveillance & Epidemiology)? There was a lot of attention paid to the public disagreement between OND and OSE at the FDA advisory committee meeting on Avandia in July.

Jenkins: ...We’re trying to make very clear that the two groups have an equal voice in evaluating safety issues and when you have two groups that have equal voice and differing perspectives, it’s not unusual that sometimes you’ll see disagreements on how to interpret the data or what the data might mean with regard to the benefit/risk...It would be odd for us to suppress those disagreements, and instead we showed the public that we do have internal disagreements sometimes about the data and we’re looking for outside input to help us better understand the data and come to a final decision. The vast majority of the interactions between OND and OSE result in agreement on the safety concerns and the course of action. It’s the minority that lead to disagreements at the end that have to be adjudicated by someone at a higher level. That’s the process we want.

RPM: Time and time again, investors tell us the number one thing they and the start-up biotech companies they fund are worried about is drug safety. Do you think this year, the fervor over drug safety will die down or is this something that isn’t going away?

Jenkins: I think it’s going to be a continuing focus for the foreseeable future.

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