Pharma Continues To Complain About The FDA
23 CommentsBy Ed Silverman // June 30th, 2008 // 7:42 am
So what else is new? In yet another round-up that discusses the slow rate of approvals compared with the number of FDA warnings, rejections and delays, The Wall Street Journal gathers some recent developments to re-examine the issue once again.
Last year, the FDA approved 19 new meds, the fewest in 24 years, and announced about 75 new or revised Black Box warnings, which was twice the number in 2004. The number of approvable letters, which postpone FDA decisions pending more data, increased by 40 percent last year, according to Sagient Research, the paper writes.
Meanwhile, pharma grouses the European Medicines Agency has approved several drugs that haven’t passed muster with the FDA, including Galvus, Prexige and Acomplia. The FDA has delayed approval of Glaxo’s HPV vaccine, Cervarix, and Schering-Plough’s sugammadex, a drug designed to be used after surgeries to undo the effects of muscle relaxants, and rejected Merck’s Arcoxia painkiller. Cervarix and Arcoxia are on the market in Europe, while sugammadex has been recommended for approval there.
Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, continues to deny the agency has become “more conservative” about safety, and tells the paper “it’s long been true that different countries looking at the same facts and data arrive at different conclusions.” She also notes new drug applications dropped 33 percent in 2006, which helps explain the decline in approvals in 2007.
Kenneth Kaitin, director of the Tufts Center for the Study of Drug Development, tells the Journal that “everything pointed to the notion that the FDA and the industry had lost their compass, and that the FDA needed a course correction,” and that FDA is now “viewed as an agency that is supposed to keep unsafe drugs off the market, not to speed access to life-saving drugs.”
By the way, we recently posted this info about the NDA approval rate this year. And Here’s the rest of the story…
Nathan
The last sentence of the article sums up all of my frustrations with the FDA: The FDA is now viewed as an agency that is supposed to keep unsafe drugs off the market, not to speed access to life-saving drugs.
pharma PR hack
Nathan,
I strongly diagree. I think the FDA is looking for the right mix of side-effects and benefit and the industry is not reading the cues well enough. The examples listed aren’t the FDA refusing life-saving meds but the FDA being harder on meds which are already in crowded classes and harder on meds that treat factors of a disease or pre-disease state such as cholesterol i.e. where the benefit has to be a higher threshold and the side-effect risk profile has to be less than what is already out there. I.e. Weight loss drugs (Accomplia), HPV vaccine (Merck’s is already out there), painkillers. Where it is supposed to keep unsafe drugs off the market!
Insider
Remember Pargluva:
In a lengthy, but most illuminating, post Roy M Poses MD takes us through both the JAMA/Pargluva issues and also a JAMA editorial by Brophy in which the following phrase rings in Insider’ ears:
“Generically, there are specific methodological decisions in the sponsor’s FDA application that may foster an illusion of safety. The following are several, perhaps unintended but nevertheless disingenuous, methods observed in the application that may have contributed to an overestimate of the safety profile:”
A list of 8 “methods” then follows.
BMS with their “partner” Merck were due to co-promote Pargluva.
http://hcrenewal.blogspot.com/2005/11/muraglitazar-case-new-window-on.html
An “illusion of safety”………!
Nathan
PR Hack writes: “I think the FDA is looking for the right mix of side-effects and benefit and the industry is not reading the cues well enough.”
That’s fair — but you can’t deny that the “right mix” is different today than it was just 5 or 10 years ago. Considering that clinical drug development is a 5-10 year process, you can’t expect drug companies to react very quickly. The products being submitted for FDA approval entered the clinic 5-10 years ago, when a completely different “mix of side-effects and benefits” was expected.
Moreover, I strongly disagree with your assertion that the FDA should be harder on follow-on products (like GSK’s HPV vaccine). We frequently do not know the true safety profile of a product until long after it has been on the market. If the FDA delays and rejects follow-ons, then it risks facing a situation where a life-saving drug is found to have after-market safety problems, but then the FDA has already turned down multiple requests for competing drugs that may not have those same safety problems. That would be a big loss for both pharma and for patients.
James
“The FDA is now viewed as an agency that is supposed to keep unsafe drugs off the market, not to speed access to life-saving drugs.”
The FDA was not established to speed access to life-saving drugs. Indeed, why would we need a bloated government bureaucracy to improve upon the speed the free market provides?
Make no mistake–the FDA is the brake, not the accelerator.
Dose of reality
First and formost, the FDA needs to protect the safety of the public, not the profits of the Big Pharma companies. Pharma has dug its own hole by not being honest and truthful. They try to pull the wool over the eyes of the FDA, the FDA gets blindsided with safety issues post approval, and the public suffers. In addition, many of the new submissions are not revolutionary - combine two agents, create an extended release formulation, do a pediatric study for additional exclusivity, add the 6th drug to a crowded class - all for more profits. What value is that to the public? Not much!
Just Rewards
Looking at the WSJ article, it appears that approvals peaked in 2004 and have dropped since. What happened in 2004? The Vioxx mess! Is it any wonder that the FDA is taking a closer look at products before approval. Fool me once, shame on you, fool me twice, shame on me. The FDA doesn’t want egg on its face again. They’re tired of not being told the whole story and now they’re taking more care with all of their reviews.
Justice
Who can really take seriously anything that comes out of Fred Hassan’s mouth at this point. He’s still trying to point fingers at anybody in the way for the ENHANCE fiasco that he and his management team got the MSP Joint Venture into earlier this year. He just wants to whine. Whoah is he - he only made $32 million last year and will likely have to take a paycut in 2008. Unless his puppets on the BOD can figure out a new way to reward he and his cronies by shafting the stockholders and the employees. I think that the guy has fallen a long way in just the past 6 months and is scrambling to try to make himself look more important when he’s practically dead wood.
Condor
Justice — re Hassan — DING! Ring the bell!
Nathan
James & Pharma Hack
RE: The role of the FDA. This is directly from the FDA mission statement on its web site. The role of the FDA is **NOT** just to be the “brakes”:
The FDA is responsible for
1) protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation.
2) advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable;
3) helping the public get the accurate, science-based information they need to use medicines and foods to improve their health.
People complain about the ineffectiveness of the FDA of part 1 of it’s mission. It’s failing just as miserably at part 2 of it’s mission!
Justice in MI
I think we may be missing the most important part of the WSJ article. It reads:
“The FDA’s Dr. Woodcock says that the quality of research coming out of the pharmaceutical industry is slowing the number of drug approvals. New drug applications submitted by the industry, she says, dropped 33% in 2006, which helps explain the decline in 2007 approvals. “You can’t approve drugs you don’t get applications for,” she says.”
Question is: True or not?
(BTW, “Justice” and I are not the same person, even if we have the same “first name”…)
Nathan
Justice in MI,
That’s the $1000 question. Unfortunately, the FDA won’t release statistics about the number of NDAs it reviews (or recieves) per year! So we just have to take her word for it…
See this article that looks at another way of analysis. Based on the number of approved drugs per ongoing clinical trial, we are at an all-time low. This would argue against Janet Woodcock’s assertion.
http://www.fool.com/investing/high-growth/2007/11/28/welcome-to-the-new-era-of-fda-regulation.aspx
Dan
Pharma complaining about the FDA is similiar to a spousal argument, as the two clearly share the same bed, from an intimacy paradigm.
pharma PR hack
Nathan you and I disagree on the actual meaning of #2- I don’t think that means faster approvals or a rubber stamp.
I take it to mean the FDA should invest more in the science of manufacturing as a basic science similar to what it does for drug development to speed up the time when approved drugs can make it to market after approval.The US should do this similar to the way it invests in defense, aerospace, etc. But in order for the industry to move to more continuous processing and stop the outsourcing that may be too late to stop.
NOT to speed up the approval of drugs- as you rightfully noted there is not a true picture of the safety of drugs is not known until later.
Jack2
The article only touched on this but here’s some numbers:
Black Box Warnings by Year:
2003: 21
2004: 28
2005: 49
2006: 58
2007: 73
Are drugs becoming much less safe, or just better studied (I think it’s the later). More importantly, as these things proliferate, at what point do these serious warnings become background noise to HCPs?
Can I name even a fraction of the 73 BBWs from 07? I’m sure I cannot.
Nathan
I wonder if a primary care physician could even name a fraction of the 73 BBWs from ‘07. I doubt it. I think they have already become “background noise”. It’s kindof like the boy who cried wolf. After a while, nobody bothers listening to the complaints anymore.
(I’m not saying the BBW issues aren’t real — I’m saying that they are now so freely issued that thier significance is being lost)
Justice in MI
Thanks for the link, Nathan. Not that I view Janet W. as a font of all truth, but since she does give a particular percentage (although a bit unclear on exactly what it is based), it is a stretch for me to conclude there isn’t at least something going on there.
During the much politicized “drug lag” - particularly as invoked in the early 90s (pre-PDUFA), retrospective analysis shows a pattern not too far from what Janet W. suggests it true today. Key also (and still) was the number of reviewers - increasing before PDUFA and already shortening review times.
In any case, some number of preemptors have championed (at least rhetorically) a beefed-up FDA, including the FDAAA that “The Fool” blames. If you read Drug and Device Law, they recurrently credit industry for initiatives leading to the FDAAA and suggest (the logic escapes me) that “plaintiffs’ attorneys” were always against.
If so, then whatever slow-down in approval is related to increased regulatory requirements can be attributed to the industry itself, at least according to their pro-preemption lawyers and would-be champions.
Of course, the historical reality here is that today’s preemptors were yesterday’s deregulators.
Just A Thought
I agree with Nathan on this point, though maybe for a different reason:
“(I’m not saying the BBW issues aren’t real — I’m saying that they are now so freely issued that thier significance is being lost)”
It must be far easier to put a warning on something than to acknowledge or actually work on fixing a problem. Slapping a label on it allows for an excuse for a severe reaction. The doctors and patients were warned after all.
I feel the same way about pharmaceutical ads though. Warnings dished out desensitizing prospective consumers to hazardous reactions. It is dangerous because people get to accepting their reactions as commonplace and may not go to their doctors, even if the ad tells them to do so.
The FDA is our protective body. In my opinion they are too quick to approve ANDAs (which I wrongly thought were only there for generic approval). The FDA needs to tighten it up, review the information thoroughly, investigate and respond QUICKLY when patients report being harmed.
ANDAs are a bad idea all around, they are a shortcut (thus the word abbreviated). NDAs with complete data and proper testing over the period of time required for a drug to reach it’s full potential is crucial to public safety, even in a copycat drugs, because no two are precisely the same.
It’s slower. So what?
Former SP
Poor Fred! he’s worried about sustaining his exorbidant quality of life - to the tune of $30 million last year alone!
Salmon
Whether the FDA is supposed to be an agency that is a partner with Pharma and speeds up access to drugs or a brake to mitigate risk (I left out new drugs and life saving drugs on purpose) is determined by Congress. PDUFA, the Best Pharmaceuticals Act for Children, and in particular FDAAA 2007 plus the other changes in the laws clearly demonstrate that Pharma Lobbying money is having an effect on the FDA’s mission. In fact it’s extremely interesting to look at the history of changes in FDA’s and CDER’s mission statement. When Bush came in that was one of the first things they changed.
When you say FDA is looking for the right mix, what does that mean? I’ve had FDA reviewers tell me rumors of being told by management “our job is to approve drugs”. In another case of which I have personal knowledge a Sr. FDA manager told an audience of > 100 reviewers when talking about advice meetings with Pharma companies ‘who are you to question a Sponsor? They’ve had months to think about it.’ In my experience these meetings are intended to present half the story and then try to rope FDA into some sort of agreement so the company doesn’t have to look into something that they know or suspect is a problem and they don’t want reviewers to find out.
If a reviewer then finds the problem when they have some time to spend on the NDA (if the drug ever comes in) then complain. If a reviewer finds the issue during the IND phase, then work with FDA management to make sure it comes in when that reviewer is busy with something else, and then have it assigned to another person.
A 6th in class doesn’t have to be safer or more effective than first in class. In fact the mantra at some companies is ‘First to market or best to market’ The problem comes when you’re 6th in class and you’re a lot less safe. This is even worse if this makes Dr’s realize that maybe # 2 isn’t safe either. When that happens you can bet Pharma will drag it out and eventually get class labeling so that you can’t tell which ones are the worst. Take a look at the recent announcement about ‘Conventional Antipsychotics’ being just as cardotoxic in the elderly as ‘atypicals’. Didn’t anyone notice how they threw pimozide (“a drug of last resort” due to cardiac toxicities), and a few others that are really atypicals but have just been around forever into the mix.
Quality of submissions goes up and down with the safety of the drug in question and even vary within an NDA and reflects what the company wants to hide. Unfortunately we’re in a period of extremely poor quality submissions. For line extensions the nonapprovals are usually due to a sponsor putting it’s D-team on the drug and they simply not doing a very good job to even do a simple submission properly. It’s not always the drug per se. Glaxo appears to have possibly just such a problem. It’s true FDA doesn’t publish # of submissions for NMEs (they do for all NDAs and the approval rate for all NDAs is around 80% and has been relatively stable over the last 30 years. Everybody on Pharma’s side just loves to cut the plots around the time after PDUFA 1 when the curve was temporarily blown. FDA has on their website the data back to 1941 and I wanted to share some graphs and other public information with Condor so that’s why I asked for a way to send anonymous information.
I think the reason FDA doesn’t publish NME submissions is because they don’t want anyone to ask about the ones that were withdrawn and why. If you withdraw an NDA for a NME you can rename the drug and come back in later and they can give it to a different reviewer. Or you can sell it to another company. Renaming a drug (i.e. generic name) also prevents most people from looking up a drug when it’s finally approved (or even during a new review) and finding out bad things about it that are public knowledge. Hasn’t anyone noticed how all the naming conventions for generic names are being changed to prevent people from associating side effects and structural relationships not only for drugs in a single class like certain antibiotics but across classes such as antibiotics, SSRI’s, anticonvulsants, etc.. Why do you think NIH stopped funding Medicinal Chemistry in the 70’s and why Mario Rocci a medicinal chemist became CEO of Glaxo and is now CEO of PPD the contract company involved with Ketek. Take a look at what other companies he’s behind and their drugs? Remember drugs to treat orphan indications don’t pay unless you have an increase in off-label use, such as an increase in toxicities from a new NME. These kind of things are predictable and a medicinal chemist with his kind of experience would know.
As for Fred Hassan and the money people being upset at him for the Organon purchase. I’m not so sure. Take a look at who the money people are for Schering, and Pharmacia/UpJohn before that, and take a look at similar drugs with similar side effects that are already on the market where maybe FDA wasn’t as aware of potential safety issues at the time they were approved as they should have been and see who the money people are behind those companies. They may not be mad at him for the due diligence and purchase, but for failing to execute afterwards.
There’s nothing wrong with Pharma making money. It’s what drives the research and the incremental changes that eventually lead to something better. If we totally throw out the me-too’s and the line extensions we won’t have new drug classes at all. The problem is excessive greed and not accepting the fact that this is a high risk business and there will be good years and bad, and trying to hide the toxicities just to protect every last dollar in sales. As a Big Big Pharma company said to me, ‘but if we put that in the label it’ll knock 10% off sales.’
BP MD
If Fred Hassan doesn’t know, then Schering-Plough is in deep trouble. It’s simple. Do high quality research and be upfront with the agency. Don’t try to dupe them by not giving them the safety details. Don’t take forever to release your results. Build trust every day and lead with integrity! Oh, you already said that. Too bad it seems that you didn’t follow your own advice. Schering-plough would be much better off. But don’t worry, most of your competition appears to have dug the same hole!
Just A Thought
Salmon, your second paragraph pretty much describes what I have thought to be the situation between Pfizer and the FDA concerning the results of their CRADA which names Dilantin specifically, released 2 months before the NMP was put out to market. And why an FDA spokesperson said they didn’t have a chance to review the data before giving approval.
It’s nearly impossible for people who are trying to regain control of seizures and recover from toxicity, while scrambling to find a med to tirate onto to make that recovery, to get attention and fight the wrongdoers. My next step, I suppose, is to try to invoke protection under the ADA.
Just A Thought
Not wanting to misquote anyone, what the FDA spokesperson said was that the FDA was unable to review the study protocols before Pfizer proceeded.
(titrate*)