What Innovation? NIH Moves Into Drug Development
27 CommentsBy Ed Silverman // January 24th, 2011 // 12:22 pm
Concerned about the slow pace at which new treatments are being developed by big pharma, the National Institutes of Health is planning to open a new drug development center by October. The move, which comes after months of planning and study, would collect more than $700 million in projects already under way at various NIH institutes.
The decision reflects growing concern that the pharmaceutical industry is finding it difficult to deliver on new breakthroughs while, at the same time, continuing to pare some research efforts in hopes of saving money. Nearly every big drugmaker faces a revenue squeeze as big sellers face generic competition and are reacting by eliminating numerous projects to juice their bottom lines.
Big pharma productivity has been declining for 15 years “and it certainly doesn’t show any signs of turning upward,” NIH director Francis Collins tells The New York Times. “I am a little frustrated to see how many of the discoveries that do look as though they have therapeutic implications are waiting for the pharmaceutical industry to follow through with them” (read background on the proposal here and here).
For the new National Center for Advancing Translational Sciences to become reality, though, the NIH will have to close one of its 27 centers which, as the paper notes, has never been done before. And so the National Center for Research Resources will be downgraded and some functions to transferred to the forthcoming drug development center. “There are some people that would say this is not the time to do something bold and ambitious because the budget is so tight,” Collins tells the paper. “But we would be irresponsible not to take advantage of scientific opportunity, even if it means tightening in other places.”
Of course, not everyone is pleased. The NIH set up a web page for feedback and the notion of dismantling the NCRR which, among other things has been a support mechanism for junior investigators through its Center of Biomedical Research Excellence. “Moving the programs currently within NCRR would risk harming what has been a program that has achieved outstanding success and recognition,” writes Judith James, the George Lynn Cross Research Professor of Medicine at the Oklahoma University Health Sciences Center.
Meanwhile, Collins prompted a carefully calibrated response from PhRMA, which tried its best not to sound defensive, but to portray the NIH move as worthwhile. “…Bold and ambitious’ proposals, such as Dr. Collins’, will be key to how we collectively progress in discovering novel compounds for addressing patients’ unmet medical needs, ” PhRMA senior vp David Wheadon, says in a statement, while noting that “our companies create the vast majority of new medicines from start to finish.”
Industry Guy
Although I am in Industry, I would love to see this happen if only to show academics how this actually works and how difficult developing a drug actually is. I get a kick out of how academic types feel industry drags its feet on developing new therapies and seem to forget we need to do this at a profit in order to stay in business. I would like to see the discussion when they do get a good compound and need to pull the trigger on a phase 3 study and see the costs associated with it as well as the risks and heads to roll involved if it fails.
RealityCheck
I agree with industry guy. Moreover, what will happen when a drug fails in phase III after the government has spend $100M on development? Will Congressional hearings be in order? Will the Washington Post print an expose on wasted federal dollars with nothing to show in return?
Duane Sherry
Develop new drugs?
Pharmaceutical companies rarely put out anything that’s new…
“New” drugs are re-treads, the vast majority of the time… Re-treads !!!
From Marcia Angell, M.D. -
http://www.youtube.com/watch?v=ouF3ISihHLM&feature=related
Many of us have lost complete faith in pharmaceutical companies.
Why?
Because Pharma has done very little to earn any trust…. That’s why !!!
Duane Sherry, M.S.
discoverandrecover.wordpress.com
Tom
National Center for Advancing Translational Sciences
Finally the wraps are off and we can assess how the Federal government intends to address the apparent – real – decline in the number of new medicines. As presently configured, the pharmaceutical industry cannot support the cost and time required for new drug discovery. Drug developers and manufacturers need an ally who can evaluate novel potential drug targets and provide enough information for pharmaceutical companies to invest in drug development. This new Center sounds exactly like the right kind of approach.
In order for National Center the Advancing Translational Sciences (CATS?) to be successful, it must be able to take naked discoveries from academic investigators and fill out their resume enough that pharmaceutical companies can evaluate their feasibility as products. This should mean taking scientists and managers, and leaders, who are already experienced in this art and putting them into this less financially volatile (hopefully) institute. Who carries out this role now? Who has experience? Well, mainly a large number of un/underemployed pharmaceutical industry scientists and managers.
Will this new Center bring in these experienced professionals? While this should be a no-brainer, I expect this new and critical part of drug discovery will be staffed by academic-type investigators. The only justification for this that I can imagine would be that the present process of drug discovery and development is wrong, broken. I don’t believe this! It is costly, time-consuming, and has a fairly low success rate, but much of that is because the end-products are ethical pharmaceuticals. These require enormous attention to detail and to safety. As I’ve mentioned earlier, this is not, and I believe should not, be the main charge of academic research. Academic research can be non-generalizable (read, not reproducible) because its function is to stimulate further research, not make a product. Furthermore, I believe that there are a large number of novel ideas, novel targets that could be worked on. The bottleneck is providing tools (compounds) and information (reproducibility, efficacy, safety, among others) in order for drug discovery and development to be objectively triggered. I don’t believe it is reasonable to ask academic or internal NIH scientists to learn to become pharmaceutical scientists overnight, or even over a 5-10 year period. Who will teach them? Are they expected, allowed, to learn from personal experience?! Staffing this new Center with academic investigators and managers will also set the stage for a politically charged battle between this Center, claiming that it has great things for pharma to invest in, and the industry saying that it doesn’t have the information it needs to start programs. What will be next, a National Center for the Development, Manufacture, and Sales of Medicines? Far-fetched? I sure hope so.
One of the best things about staffing this Translational Sciences Center with a goodly percentage of pharmaceutical research professionals is that so many are currently very available… They can probably be snatched up for 70-80c on the dollar… On the other side, Federal stimulus funds have allowed many universities to hire more assistant professors and postdocs so that the academic community doesn’t have as strong a need for new positions.
I call for more pharmaceutical professionals for this important Center for another reason, success. The NIH Genome project was touted to provide a plethora of new medicines. With the huge, and possibly unnecessary, outlay of Federal funds, the medicines are yet to come. Even at the time of the Genome project it was clear that determination of physiological function would be necessary in order to prioritize gene products as potential drug targets. This type of effort was going on, slowly, in some academic labs, and, in a much higher throughput manner in some companies. So, belatedly, NIH started programs like KOMP, the knock-out mouse project. But, again, the reality is that huge sums of money were spent for KO mice that in many cases already existed, delaying any chances for success stories for years. Sure, there are lots of reasons for why NIH had to reinvent the wheel, but I maintain that those reasons were/are mainly hypothetical as no one – almost no one – has worked with enough KO mice to understand the real hurdles. If NIH, and friends, has to reinvent translational sciences, it is likely that a large amount of money will be needlessly spent, and the delay to real successes will be long. [As an aside, KO mice, mice in general could provide a very nice, and presumably less costly, vehicle for most pharmaceutical testing. However, the industry is built on years of experience with rats. Let NIH, and industry, work to either solidify KO rats as a general tool, or build up a large amount of disease model and toxicology data on mice!]
I fully believe in and support the need for a Center for Advancing Translational Sciences. I only hope that it will provide answers and not just a call for a National Center for Developing, Manufacturing, and Selling Medicines in a couple of years.
Paul
Academics don’t have a clue what it takes to develop and approve a drug. They think it’s easy and their perception of quality data doesn’t even come close to industry standards.
Greg Pawelski
In a TheScientist.com article, “Crowdsourcing Drug Discovery,” it was commented that for the last 50 years, randomized controlled trials have been the unquestioned gold standard, when in fact they have become a fiercely defended relic of our ignorance in 1962 when Congress empowered the FDA to begin regulating efficacy.
At that time, it was a “best we could do” solution - but now? They take too long, cost too much, are fraught with unsolveable ethical problems that patients and many physicians dislike, and cannot ask the
patient-specific molecular questions we now know need to be asked and answered.
Yet, most clinical trialists and the FDA cling to these crude, simplistic tools like an irrational safety blanket. If we can’t reach agreement that clinical methodologies must adapt to new knowledge of the biology of disease, and that the way drug development is regulated must rapidly adapt in much the same way, then our ability to accelerate advances in medicine will remain stagnant.
A key point in this article is that the new system should be patient-centric. It has to be something patients will not only tolerate, or enter under duress, but rather a system that makes sense to them personally - even when they are not yet facing a serious or terminal condition. If real patients are left out of the process of change, we will likely end up in the wrong place again.
As outlined in a presentation at the American Association for Cancer Research (AACR) annual meeting titled, “Functional Profiling of Human Tumors in Primary Culture: A Platform for Drug Discovery and Therapy Selection,” cell function analysis of human tumors provides a novel, real-time view of how such tumors act within their natural microenvironment. This information can, in turn, accelarate the drug development process and improve clinical therapy.
The analysis is unique in that each micro-spheroid examined contains all the complex elements of tumor bio-systems found in the human body and have a major impact on clinical response. Cell function analysis is a conduit that connects novel drugs to clinicians and patients in need. Appropriate use of this platform has the potential to save the pharmaceutical industry millions of dollars, shave years off the drug development cycle and improve clinical therapy.
Curious
Does this mean that the NIH will hire their own reps to promote to Dr’s as well?
Betsy Jacobson
The NIH and the Feds clearly do not understand the myriad problems that Big Pharma has invented and cast upon itself in its dedication to the bottom line.
Please, Marcia Angell, MD, get us out of this mess.
Anne PME
So, the republicans are now in control of the house and on a mission to control and cut spending and limit government. Maybe NIH could propose selling the TV rights of the NIH congressional budget talks to help out with funding shortfall?
harpy
I thought it was all FDA’s fault.
Justice in MI
Besides the size of the initiative, how is this different from what has been going on for years re: NIH, not to mention academia, participating and initiating new drug development?
Some of the commentators above apparently never heard of “transfer of technology,” or I am completely missing the point.
Help me out.
In the meantime, it will be interesting to see what drugs/conditions NIH focuses on relative to industry.
Nathan
This, in a way, is rather humorous. The US government is “concerned about the slowing pace of drug discovery” so they start up their own division to do it themselves? Since when (EVER) has government investment been able to do something more efficiently or effectively than private industry? And hasn’t drug-discovery been an underlying goal of the NIH and NCI all along?
I’m going to laugh my butt off when the government develops a “me-too” drug and claims some element of superiority over a PhRMA-developed drug. I’m ESPECIALLY going to find it funny when Teva swoops in and challenges the IP claims around a government compound and wants to make a generic drug after only a few years on the market!!
What’s next? Are we going to have the NSF form new “fuel cell car” division since the auto manufactures can’t come up with a truly electric car quickly enough? Hmmm.
Nathan
By the way, Ed, the picture you posted along with this article is an accurate reflection of my feelings about this announcement! Good choice!
industry insider
I would answer the question with a quote from one of my favorite congressman: “If the Federal Government were put in charge of the Sahara Desert, in five years there would be a shortage of sand”.
jamzo
expansion of nih mission and an expansion of govt support for pharma research?
Nathan
Actually, there is one “justifiable” reason for doing true drug-discovery at a government level:
One can make the argument that “non-profitable research” SHOULD be done in a government setting. Think about space flight (NASA) and defense research (Manhattan project, stealth technology, etc). In both of those examples, the research being done will likely never “pay off” - so there is no reason that the private sector would do the work.
You can make a fairly strong argument that drug-discovery research is rapidly entering the same sort of status: The costs and risks of drug-discovery are going up exponentially while the rewards are going down (and are likely to go down much further as government purse string tighten up in coming years). As such, drug-discovery research may rapidly be moving towards a “non-profitable” model, similar to space flight and defense research. The major “PhRMA” companies out there might simply be “PhMA” companies that just license drugs from the government and give back a portion of the profits to the government!
The moral of the story: I shouldn’t bad-mouth the government too much — they may be writing my paycheck if I stick in this industry another 5-10 years!
JaT
If a bad product is developed with the help of NIH can there be recourse? You can’t fight City Hall (I’ve tried because of CDER). Maybe drug makers should be celebrating what I believe is a step closer to preemption - it is what drug makers wanted, isn’t it? Look at the bright side - you have a good way to pass-the-buck and enjoy certain government protections from suits for the products you will manufacture.
:/
Mutatis Mutandis
Having spent ten years in the pharma industry, I am not so sure that government could not do it as well or even better… Frankly the industry has in part to blame itself for its declining productivity. So much of our work is unsystematic, throwing away the hard-won lessons of the past for the layest hype or the latest fad propagated by management consultants. Perhaps non-profit institutions, working under different constraints, will at least try different things.
I agree that the arrogant attitude of academic researchers towards drug discovery and development is going to cost them dearly. There has already been a lot of wasted effort. However, at least some of the research institutes have also contributed a lot to advancing the science of drug discovery, bringing in new tools and methodologies… Not all of it is going to work, but at least it is a breeze of innovation. Let us give new models a chance. A big gamble on genomics is probably not original enough to contribute much, but we I hope we will see some diversity in the projects funded.
But I do expect problems when civil servants will have to justify to the taxpayers the vast amounts of money spent on failed projects, as will inevitably happen if the government enters drug discovery. In industry you’re supposed to know that that is the nature of the business, and shrug it off. Congress may not be so lenient.
Angry PharmD
The govn’t thinks they can do something better and more efficiently than private for-profit big pharma? With that sort of arrogance, how can they possibly fail?? ….This is going to be a riot to watch for those of us who actually work in drug development!
My prediction:
Nothing of significant importance will get discovered, and they will hemorrhage hundreds of billions of dollars of taxpayer money.
cliffintokyo
Reminder: HHS believes not enough promising academic medical research projects are being given a shot at getting translated into real products. Supporting translational R&D will hopefully feedback to academia to help focus on starting more projects that have an eye on potential medical products downstream, and decrease the number of pie-in-the-sky projects.
The money to be spent is only a tiny amount compared with the academic funding that is used to churn out citation-fodder but worthless research publications.
Outside the Box
I think we should all hold our breath for just a second. What if the new operation works as an extension of the generally successful approach taken for years in providing SBIR funding to start-ups by allowing funding to go into the full development process with a larger Government royalty on commercial returns? If this was also combined with the new view at the FDA that rolling trials based on Bayesian rather then frequentist statistics would allow for much faster, smaller and cheaper studies, leading to earlier go/no-go decisions. Big pharma could at last get out of the part of the business that it is bad at and focus on what it does best.
Think I’m smoking something funny - just wait and see….
Salient point
The FDA being forced to try to honestly evaluate a product that’s been developed, at great expense, by a sister agency.
Medicare fighting with a sister agency–in federal court!–over pricing & generic issues.
I see all kinds of fun & games coming out of this. Let’s get the popcorn ready!
Nathan
Salient point - exactly correct. People are so concerned with “conflicts of interest” in the pharma industry. This has the potential to make us wish for the “good-old-days” when COI’s merely existed between doctors and pharma!
CR
It’s interesting to read this blog (and others) with the industry individuals coming along with their “if we can’t do, nobody can” attitude. As someone who has worked in the pharma industry I have very little confidence in any company bringing a drug to market from scratch (ie, target validation, HTS, drug design, medicinal chemistry, etc.). Not that they are not capable of doing this anymore, but their management makes it nearly impossible for this to happen. Timelines change, desire changes, risk aversion happens, etc. 10+ years ago I would have agreed with those industry insiders (Nathan, Angry PharmD, Industry Guy et al.); but the knowledge it takes to do this is no longer contained within the industry walls. There have been so many lay-offs, RiF’s, etc. that there are many individuals out there with the knowledge and experience to be successful.
That being said I don’t believe Dr. Collins is proposing a government controlled pharma company (and I’ve heard him speak about this on several occasions). What he is proposing is an attempt to “de-risk” drug discovery for the pharma industry. If pharma is anything (and they are not discovery engines anymore) they are drug developers. This new center would simply give the resources to individuals to further validate a target, molecule, etc. In one instance that may mean more money for target validation, in another it may mean money for FiM studies to show to a pharma company the target/molecule is worthwhile. Pharma would be (for the vast majority of cases) driving the product through trials/development, not the government.
It’s just interesting the complete disregard from industry individuals when they (the companies not individuals) have been utterly failing over the past several years. And Dr. Collins is correct, there is nothing to show that trend is going to reverse itself. Will it be successful? If the correct goals are initiated (ie, de-risk) then I don’t see why it wouldn’t. Are there going to be failures? Sure, name me a single company that hasn’t seen failure recently.
My two cents.
New Drugs Book
I’ve led a number of successful drug development programs, including blockbusters, like Aricept, the main drug used to treat Alzheimer’s disease. These were cheap and fast. All of them got approved. It really isn’t that hard, if you know what you’re doing and have some experience and experienced people on the development team. I’ve outlined how I did it in the book I wrote.
The problem with new drug development has nothing to do with science. The science now is better than ever. I completely agree with many of the industry people above. The problem is management of the process. Many companies have contracted out clinical development, so they have lost control of that process. They license in only late-stage products, effectively outsourcing discovery. Frequently tox is also outsourced. So, what’s left in a company? Just functionaries. All the discovery and development expertise is lost and the synergies of having experienced, productive, creative people all under the same roof are gone.
The result is as described in the post above, ineffectual management, wasted resources and very, very high costs.
Most companies lack experience and the management commitment required to get through the process efficiently. That’s the problem. It’s easily solved. It only took me a few million dollars and two or three years to turn around a big company. So, the problem will be solved. Maybe the government will solve it, maybe a few small companies will grow big enough to take up the slack, maybe philanthropic organizations will fill part of the gap or maybe many of the larger companies will finally get their act together. It’s just a matter of time and who get’s their act together first.
industry insider
NDB, I completely agree with you. One thing that I’ve learned over the years is that if you know what you’re doing in drug development you can get XYZ drug approved, whereas if you don’t know what you’re doing you can fail to get the same XYZ drug approved. I’ve seen it happen many times. Also it used to be that pioneer companies such as Merck would spend the most industry time in Phase II, looking at more than one indication and doing multiple studies. They would not take a drug into Phase III unless there was 95% probaility of success. Today, companies rush through Phase II and basically go into Phase III on a wing on a prayer, hoping to jack up the stock price or obey orders from marketing. The result? Much higher and costlier failure rates in Phase III then we’ve seen in the past.
Jon
In their recent, widely-acclaimed paper: The Role of Public-Sector Research in the Discovery of Drugs and Vaccines NEJM | February 9, 2011, Stevens et al said:
“We believe that our study supports the concept that the emergence of biotechnology in the mid-1970s, combined with policy changes implemented in the early 1980s regarding the ownership and management of the intellectual property of PSRIs, allowed these institutions to play an important role in the downstream, applied phase of drug discovery. Our data show that PSRIs have contributed to the discovery of 9.3 to 21.2% of all drugs involved in new-drug applications approved during the period from 1990 through 2007. These proportions are higher than those identified by some earlier researchers.
Our data also suggest that PSRIs tend to discover drugs that are expected to have a disproportionately important clinical effect.
This would put a lie to Wheadon’s comment above that “our companies create the vast majority of new medicines from start to finish.”
I think this should be put to him in no uncertain terms.