Biocentury has a really good interview with John Jenkins, who’s departing the FDA this week after 15 years as director of the Office of New Drugs at the agency’s CDER (Center for Drug Evaluation and Research). Any drug that’s been through the regulatory process during that time has gone across his desk, so he’s seen a lot, and he has some interesting things to say.
One remark that’s gotten a lot of attention refers to the way that (some) companies treat disclosure of FDA communications, such as CRLs (Complete Response Letters) when a drug is turned down. These are not made public; it’s up to the companies themselves to issue what information they well. And you know what? Some of them lie about it. That’s the only conclusion one can draw from this:
How often have you encountered situations where the statements companies made about their interactions with FDA weren’t accurate?
JJ: It’s pretty frequent. And as you know I’ve been an advocate for many years for greater transparency of sharing the communications and the interactions we have with companies, making those publicly available, because our communications are often not as clearly communicated by what companies say to the public as I think they should be or could be.
BC: I realize you can’t talk about specifics, but can you talk about the kinds of things companies say that are inaccurate?
JJ: Let’s say we have an end-of-Phase II meeting when we are giving advice on a Phase III program. Maybe the communication that the company gives to the public is much rosier than the actual advice or feedback we gave on their development program. Then later if the perception is that things didn’t work out for them as well [as they’d hoped] then the perception is why did the FDA give you such rosy advice in the past.
Another example would be downplaying the deficiencies in a [complete response] letter about what the agency said and what additional work they need to do. Sometimes companies claim when they get a CR letter that they were caught by surprise, that the agency had never raised these issues before, and that’s not true. I’ve heard companies make statements that they were blindsided by the agency raising an issue and it’s often not true.
Investors should keep this sort of thing in mind – you’d think that it wouldn’t be legal or wise for a company to just come right out and misrepresent what the FDA has told them, but under the current system that’s just what can happen, and often seems to happen without penalty. Experienced drug developers look at these situations and can guess that someone’s not being truthful, but smaller investors and the patient community won’t realize what’s happening.
It’s easier for a company to blame Evil Regulatory Obstruction, but a big problem with that strategy is that people get a distorted view of the world. Many people (and many politicians among them) seem to imagine that there’s this big logjam of wonder drugs that’s having to work its way slowly through a thin hallway full of persnickity bureaucrats – if only we could open those floodgates! But this isn’t actually the case. If you look carefully at the number of New Drug Applications, it’s hard to make the case for a giant backlog. Now, another possibility is that if the drug approval process were faster and easier, that more investment would flow into the sector and more new drugs might eventually be the result. That’s not a crazy thought, but it’s not a complete picture of reality, either.
One big question that has to be asked in this case is how one makes the process faster and easier, while still having some expectation that said new drugs do anything for patients while not doing them actual harm. You’d think (if you haven’t done this stuff) that these questions could be answered a lot faster than they are now, but actually doing that a lot faster is really difficult. Designing clinical trials, recruiting patients, running the trials on a scale and in a way that can provide meaningful answers, and working up the data: all these things take more time than anyone who hasn’t done them can believe. “Come on! Does this drug work or not?” is the usual question, but the frustrating usual answer is “Well, we’re still trying to figure that out”.
Keep in mind that most drugs aren’t amazing slam dunks in the clinic, unfortunately, even the ones that were supposed to be. That brings up another key point: FDA approval is not the rate-limiting step for producing a truly new drug. The rate-limiting step for breakthroughs is the science, the flippin’ science. Having an idea about a new therapy, getting something that’s even remotely worth taking to the clinic in the first place – those are the long and hard steps, because they’re completely undefined and wide open. The paths through the clinic and through the FDA are much better laid out, but there is no path through the early-stage research. You have to make one.