A dry drug pipeline

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The research pipeline is full of junk. More monoclonal antibodies with limited efficacy....specialized chemotherapy on the newest receptor pathway (JAK)...and more rehashes and drug combos.

We're only getting 1 new abx a year....pitiful.

Oh look, another insulin analog. Great stuff!

And then we have this Alzheimer's marker that doesn't haven great diagnostic accuracy.

Such a shame.

SGLT2 inhibitors could be big for diabetes.

NXL-104 is a b-lactamase that's effective against KPC.

That's really all that I can think of, though. Very few drugs are still on patent too. What happens to big pharma when all their drugs are generic? No revenue means no R&D.

Maybe the law of diminishing returns applies to drug development moreso than say, Moore's law.

For years, I wanted to go into pharma preclinical research. I somewhat recently got a PhD in pharmacology, but the career for scientists is terrible now and for the foreseeable future (few jobs, job insecurity, outsourcing, long hours, low pay...). Pharma has 300,000 fewer jobs in the US than in 2003. That is a huge number for an industry that probably only has around 1,000,000 people in the US. I am starting pharmacy school in august. I know the market for pharmacists isn't that great, but I don't want to teach high school chemistry.

There are many reasons for the empty pipelines. Primarily, I'd argue that it is due to generic competition. Not only does your drug have to work, it has to work better than all of those cheap generics for it to be prescribed and for you to recoup your investment. The drugs that we have for many indications are decent for most people. Showing efficacy is hard enough-showing superiority over good drugs is costly and damn near impossible. Hence, companies are not pursuing drugs for many common indications with lots of generic competition.

Also, the FDA is insanely cautious, governments are limiting what you can charge, our understanding of the biology is inadequate (i.e. Alzheimers), reductionist approaches to research are overly simplistic (most diseases are not controlled by one protein/gene), there are lots of good drugs available, recouping your investment is terribly difficult unless you have millions of patients or charge the very few patients hundreds of thousands a year, the industry has been consolidating for over 10 years (fewer companies looking) . . .

Ironically, it was a banner year for drug approvals ... onc and hep c have exploded in the last few years (and months, in the case of hep c)

Originally Posted by Argentium

Ironically, it was a banner year for drug approvals ... onc and hep c have exploded in the last few years (and months, in the case of hep c)

But how many patients have hep C? Sure it's a somewhat sizeable amount, but nowhere near that of dm, htn, pain, etc.

Originally Posted by gadlo

For years, I wanted to go into pharma preclinical research. I somewhat recently got a PhD in pharmacology, but the career for scientists is terrible now and for the foreseeable future (few jobs, job insecurity, outsourcing, long hours, low pay...). Pharma has 300,000 fewer jobs in the US than in 2003. That is a huge number for an industry that probably only has around 1,000,000 people in the US. I am starting pharmacy school in august. I know the market for pharmacists isn't that great, but I don't want to teach high school chemistry.

There are many reasons for the empty pipelines. Primarily, I'd argue that it is due to generic competition. Not only does your drug have to work, it has to work better than all of those cheap generics for it to be prescribed and for you to recoup your investment. The drugs that we have for many indications are decent for most people. Showing efficacy is hard enough-showing superiority over good drugs is costly and damn near impossible. Hence, companies are not pursuing drugs for many common indications with lots of generic competition.

Also, the FDA is insanely cautious, governments are limiting what you can charge, our understanding of the biology is inadequate (i.e. Alzheimers), reductionist approaches to research are overly simplistic (most diseases are not controlled by one protein/gene), there are lots of good drugs available, recouping your investment is terribly difficult unless you have millions of patients or charge the very few patients hundreds of thousands a year, the industry has been consolidating for over 10 years (fewer companies looking) . . .

As bad as everyone fears the market is for pharmacists, it's a lot worse for those wanting to go into industry. I was a part of the million in 2003 and am now a part of that 300,000. Who knows what the Big Pharma landscape will look like in 10/20 years.

Originally Posted by Flavoring Agent

The research pipeline is full of junk. More monoclonal antibodies with limited efficacy....specialized chemotherapy on the newest receptor pathway (JAK)...and more rehashes and drug combos.

We're only getting 1 new abx a year....pitiful.

Oh look, another insulin analog. Great stuff!

And then we have this Alzheimer's marker that doesn't haven great diagnostic accuracy.

Such a shame.

LOTS of reasons the pipeline has dried up: easy things already done, poor decisions by pharma leadership, legal environment, etc. But there is only 1 reason that there are so few new ABXs and that is the dim whited, silo mentality pharmacists who ONLY looks at drug acquisition costs.

If the Ford Motor company were told people could only buy their new car after folks cars broke down, would shareholders keep giving them money to build cars? We can't expect pharma to invest in a very risky game to get an antibiotic out in 12 years only to have some imbecile restrict it and kill it commercially. Be intellectually honest, even if you hate drug reps. Why would a company do it?

Originally Posted by StewardshipDude

LOTS of reasons the pipeline has dried up: easy things already done, poor decisions by pharma leadership, legal environment, etc. But there is only 1 reason that there are so few new ABXs and that is the dim whited, silo mentality pharmacists who ONLY looks at drug acquisition costs.

If the Ford Motor company were told people could only buy their new car after folks cars broke down, would shareholders keep giving them money to build cars? We can't expect pharma to invest in a very risky game to get an antibiotic out in 12 years only to have some imbecile restrict it and kill it commercially. Be intellectually honest, even if you hate drug reps. Why would a company do it?

Antibiotics are restricted because of drug resistance. Restricting the antibiotic is a fantastic idea because the use of the drug will invariably produce resistant strains (i.e. MRSA, VRSA, drug resistant gonorrhea, drug resistant tuberculosis...). However, we need to provide different funding mechanisms for companies to stay in the game and do this desperately needed research. Unfortunately, nothing is happening and hardly any companies look for antibiotics.

Word. Another scientist that is finishing her P1 year. The approved drugs are from research done in 1997. Takes 15 years and 1 Billion dollars to get a drug through FDA. They cut research to the bone in the 2000s. Nothing left. Darn lawyers. Who cares about the 999,999 if 1 has a problem.

Originally Posted by gadlo

Antibiotics are restricted because of drug resistance. Restricting the antibiotic is a fantastic idea because the use of the drug will invariably produce resistant strains (i.e. MRSA, VRSA, drug resistant gonorrhea, drug resistant tuberculosis...). However, we need to provide different funding mechanisms for companies to stay in the game and do this desperately needed research. Unfortunately, nothing is happening and hardly any companies look for antibiotics.

This. You have to keep drugs in the arsenal otherwise we may all be screwed!

Fools, we should use the most expensive agents so that drug companies will bless us with new drugs. We shouldn't use generics at all. Dummies.

Originally Posted by owlegrad

Fools, we should use the most expensive agents so that drug companies will bless us with new drugs. We shouldn't use generics at all. Dummies.

Shortsighted. When there are no drugs for your condition anymore because of resistance and It will take 15 years to develop a new one.... whoops, sorry.

I'm not saying drug companies aren't evil ... of course they are, but they do serve a need.

Originally Posted by chemnerd99

Shortsighted. When there are no drugs for your condition anymore because of resistance and It will take 15 years to develop a new one.... whoops, sorry.

I'm not saying drug companies aren't evil ... of course they are, but they do serve a need.

Sarcasm fail.

I love it.

Originally Posted by rxlea

Sarcasm fail.

He sarcastically said "don't use generics" which really means "use generics."

Chemnerd disagrees and says "don't use generics"

If he missed the sarcasm, he would've said "I agree!"

Originally Posted by Ackj

He sarcastically said "don't use generics" which really means "use generics."

Chemnerd disagrees and says "don't use generics"

If he missed the sarcasm, he would've said "I agree!"

I read it differently lol

I caught the sarcasm, I'm the queen of sarcasm. I'm currently interning for the poor hospital in town so I understand the need for generics. Yes the pills are 5 cents each to make but the first one cost 1 billion dollars. If its all generics, generics, generics where is the next new drugs coming from. You can't have it both ways.

Originally Posted by StewardshipDude

LOTS of reasons the pipeline has dried up: easy things already done, poor decisions by pharma leadership, legal environment, etc. But there is only 1 reason that there are so few new ABXs and that is the dim whited, silo mentality pharmacists who ONLY looks at drug acquisition costs.

If the Ford Motor company were told people could only buy their new car after folks cars broke down, would shareholders keep giving them money to build cars? We can't expect pharma to invest in a very risky game to get an antibiotic out in 12 years only to have some imbecile restrict it and kill it commercially. Be intellectually honest, even if you hate drug reps. Why would a company do it?

You can't be serious. Either that or you're a Dapto/Zyvox rep.

If you truly believe pharmacists only look at acquisition cost, then you're the one in the silo. It's amazing to see how bitter you're at the admin who preaches cost effective treatment. Today, in an ever decreasing reimbursement and ill adjusted payor mix, hospitals have to do whatever they can to survive so you can get paid and your patients can be treated. I was involved with 4 hospital closures. It's not fun.

What is the definition of stewardship? It's a responsible management of resources and the goal of antibiotic stewardship is to prevent resistance, enhance clinical outcomes, and manage cost. It doesn't mean everyone gets generic cipro nor every MRSA gets Dapto..

Appropriate and cost effective treatment that results in best outcome is what we shoot for..not lowering the antibiotic cost at all cost.

Your bitterness is pathological. Kinda funny.

Question: The premise of this thread seems to be the drug research market in the USA. I know that the US has a legacy of researching the lion's share of drugs for market. However, it seems that other parts of the world (Europe in particular) now seem to be picking up the slack. Thoughts? Will the next cipro come from Europe?

Originally Posted by xtsukiyox

Question: The premise of this thread seems to be the drug research market in the USA. I know that the US has a legacy of researching the lion's share of drugs for market. However, it seems that other parts of the world (Europe in particular) now seem to be picking up the slack. Thoughts? Will the next cipro come from Europe?

Many major drug companies are European...Bayer, Sanofi, novartis, boehringer ingelheim, Roche, astra zeneca, Glaxo .....

Originally Posted by rxlea

I read it differently lol

As did I. The only way that response makes any sense to me is if chemnerd thought I was serious. Isn't he saying that it is short sighted to use brand name antibiotic irresponsibly? That was the point of my sarcasm.

But it is hardly important either way.

Originally Posted by Ackj

But how many patients have hep C? Sure it's a somewhat sizeable amount, but nowhere near that of dm, htn, pain, etc.

Orphan Diseases (which Hep C and most cancers aren't by a long ways) are really popular right now because the science is picking up and the FDA is providing great incentives - they are working on similar incentives for antibiotics as well btw.

And also there are some great cv meds in the pipeline. Take a look. Roche has one and so does Merck I believe (?)

Originally Posted by chemnerd99

Word. Another scientist that is finishing her P1 year. The approved drugs are from research done in 1997. Takes 15 years and 1 Billion dollars to get a drug through FDA. They cut research to the bone in the 2000s. Nothing left. Darn lawyers. Who cares about the 999,999 if 1 has a problem.

AZT, the first antiretroviral, was developed as a cancer drug in the 1960s and declared to be ineffective relative to its side effect profile. HIV came along, or rather our knowledge of it did (see my footnote) and it was dusted off, tested, and found to work.

Footnote: I'm currently reading a very interesting book called "Tinderbox", which explores some theories about the origin and spread of HIV. The author believes that somewhere in southern Cameroon, the HIV virus entered the human population, most likely from a hunter injured while butchering an infected monkey, sometime between the 1880s and early 1920s. I figured out the "cut hunter theory" quite a few years before I read it anywhere else.

Originally Posted by Flavoring Agent

The research pipeline is full of junk. More monoclonal antibodies with limited efficacy....specialized chemotherapy on the newest receptor pathway (JAK)...and more rehashes and drug combos.

We're only getting 1 new abx a year....pitiful.

Oh look, another insulin analog. Great stuff!

And then we have this Alzheimer's marker that doesn't haven great diagnostic accuracy.

Such a shame.

If you're so passionate about this view, why not be proactive and do something about it? There's nothing stopping you from going into research. Come up with the next big idea instead of complaining about how the pipeline is junk.

Originally Posted by gadlo

Also, the FDA is insanely cautious, governments are limiting what you can charge, our understanding of the biology is inadequate (i.e. Alzheimers), reductionist approaches to research are overly simplistic (most diseases are not controlled by one protein/gene), there are lots of good drugs available, recouping your investment is terribly difficult unless you have millions of patients or charge the very few patients hundreds of thousands a year, the industry has been consolidating for over 10 years (fewer companies looking) . . .

Can you give an example where the FDA was so cautious it should be considered insane?

Originally Posted by Ackj

But how many patients have hep C? Sure it's a somewhat sizeable amount, but nowhere near that of dm, htn, pain, etc.

More patients now die of Hep C than HIV.

Originally Posted by chemnerd99

Word. Another scientist that is finishing her P1 year. The approved drugs are from research done in 1997. Takes 15 years and 1 Billion dollars to get a drug through FDA. They cut research to the bone in the 2000s. Nothing left. Darn lawyers. Who cares about the 999,999 if 1 has a problem.

Don't make FDA out to be the bad guy. It takes time and money to show a new drug is safe and effective. Period.

Originally Posted by xtsukiyox

Question: The premise of this thread seems to be the drug research market in the USA. I know that the US has a legacy of researching the lion's share of drugs for market. However, it seems that other parts of the world (Europe in particular) now seem to be picking up the slack. Thoughts? Will the next cipro come from Europe?

The drug research market is global. Even US companies developing a drug primarily for the US market do much of the clinical research overseas due to cost.

Originally Posted by Brock Landers

The drug research market is global. Even US companies developing a drug primarily for the US market do much of the clinical research overseas due to cost.

If this is the case, why would US policy be such a deciding factor for new drugs in the "research pipeline?"

Z, I didn't mean to say that the companies aren't European - I was, on some level, countering the heavy intimation that the US market dictates new drugs. This is probably a case of ignorant myopathy on my part.

Originally Posted by Brock Landers

More patients now die of Hep C than HIV.

Nobody dies from HIV, they die from resulting neutropenic coinfections. I know what you mean, but I'm not certain that it's really an issue of prevalence but rather current treatments. We have quite a few effective HIV meds now, and in the past few decades we've learned a lot about it. Hep C never really is a big news story, and doesn't have a lot of options (until recently), so that may explain the survival differences.

Originally Posted by rph3664

The author believes that somewhere in southern Cameroon, the HIV virus entered the human population, most likely from a hunter injured while butchering an infected monkey, sometime between the 1880s and early 1920s. I figured out the "cut hunter theory" quite a few years before I read it anywhere else.

I like that theory about jumping hosts a lot better than the other commonly imagined one. You know, the one about it being an STD.

Originally Posted by Ackj

Nobody dies from HIV, they die from resulting neutropenic coinfections. I know what you mean, but I'm not certain that it's really an issue of prevalence but rather current treatments. We have quite a few effective HIV meds now, and in the past few decades we've learned a lot about it. Hep C never really is a big news story, and doesn't have a lot of options (until recently), so that may explain the survival differences.

I like that theory about jumping hosts a lot better than the other commonly imagined one. You know, the one about it being an STD.

Hep C is not a big story because you live in the USA. It is a huge issue in emerging markets (particularly in asia) which is where pharma is focusing right now.

xtsukiyox: Brock Landers is absolutely correct in that clinical trials are global and have sites from many different countries in the world with the goal of getting a simultaneous (or as close to possible) approval in the EU, USA, Japan.

US policy is a deciding factor in drug approval for some pretty obvious reasons (1) it is the largest single market for most drugs and (2) the FDA (for all the bashing) is an excellent institution and is a bell weather for the rest of the world

Originally Posted by Ackj

But how many patients have hep C? Sure it's a somewhat sizeable amount, but nowhere near that of dm, htn, pain, etc.

Hep C is at an interesting point in time right now. Newly acquired infections are much lower than they were historically, so once the current generation of patients dies/is cured, the potential market is going to be an awful lot smaller. The companies are rushing to get their drugs on the market before it disappears.

Originally Posted by Praziquantel86

Hep C is at an interesting point in time right now. Newly acquired infections are much lower than they were historically, so once the current generation of patients dies/is cured, the potential market is going to be an awful lot smaller. The companies are rushing to get their drugs on the market before it disappears.

Totally agree. I believe we're on a verge of making HEP C a controllable disease.

the cancer pipeline is LOADED and costing 10k per month, that is not a sustainable model and something will have to change

hep C looks promising, but these drugs are $$$ also

Originally Posted by lorain

the cancer pipeline is LOADED and costing 10k per month, that is not a sustainable model and something will have to change

hep C looks promising, but these drugs are $$$ also

survival rate for the new Hep C treatment seems a lot more promising than the new "MABs"

Originally Posted by Its Z

survival rate for the new Hep C treatment seems a lot more promising than the new "MABs"

We're at the same point with HepC that we were at with HIV 20 years ago. There's decent drugs on the market, but overuse/misuse might take away a lot of the benefit of the REALLY good stuff that's just a few years down the road. I hope that hepatologists can see that and hold off before they really start going for broke with using boceprevir and telaprevir.

All of the Hep C injectable interferons are requiring insurance PAs. Kinda sucks

Originally Posted by xtsukiyox

If this is the case, why would US policy be such a deciding factor for new drugs in the "research pipeline?"

Because the US is the only (or biggest) market where paying drug companies for brand names at high prices is practically institutionalized . ex: medicare part D and the drug company handouts in the ACA. And FDA is very picky.

There is an over-prescribing problem of antibiotics in the United States. We may find ourselves in trouble if there isn't enough new antibiotics in the pipeline to replace the existing ones. Look at azithromycin as an example. Every Joe and Jane that goes to their doctor or urgent care with the sniffles gets a Z-Pak. What happens when that medication doesn't work anymore?

Research is down for big pharma but the landscape of drug development is changing. Now you see more pharmaceutical companies partnering with a biotech company for research and development. This allows the pharmaceutical company to focus more on safety, approval, and marketing and leaves the research and development aspect to the biotech company. I think you'll see a lot more partnership agreements between different companies for the purpose of drug developments in the future.

And don't underestimate the regulatory impact on drug development. Some of the most promising new frontiers of medicine including stem cell research and gene therapy are all dependent on a favorable regulatory environment. We haven't scratched the surface of what is possible in the field of medicine and now that the genetic code has been cracked, the sky is the limit.

Originally Posted by Brock Landers

If you're so passionate about this view, why not be proactive and do something about it? There's nothing stopping you from going into research. Come up with the next big idea instead of complaining about how the pipeline is junk.

Can you give an example where the FDA was so cautious it should be considered insane?

The pipeline isn't dry because of the lack of good ideas. The pipeline is dry because we have a lot of good drugs for the major indications (that means no more blockbusters), the cost of getting a drug to market is in the billions, the FDA is very cautious (and this means $ in lost time, more, and longer tests and trials), reimbursement hurdles, government intervention, incomplete understanding of the biology and toxicology, etc. We still have tons of great ideas, but it is too costly for companies to pursue many of them relative to the risks and predicted returns.

Please forgive my momentary, internet hyperbole. The FDA is not insane. The FDA has become very cautious in many indications. Getting a drug through is very difficult. Aspirin would probably not get through this current regulatory environment. The biggest example of a cautious FDA is the amount of time a drug/product spends under regulatory review. In 1962, a drug spent less than one year from the investigational new drug application (IND) to approval. In 1998, it was over seven years. The number of clinical trials required has become greater and the number of patients required per trial is larger. All of this means money. The cost of bringing a drug to market is $1.3 billion. But consider that most companies have more misses than hits. If you count the costs of pursuing drugs which don't receive approval under the total costs, that amount goes up to around $4 billion (http://www.forbes.com/sites/matthewh...ing-new-drugs/). Why would anyone spend that kind of money for their drug to not be prescribed because there are 20 generics for that same indication? That is why we are seeing so much focus on orphan diseases. That new drug kalydeco for cystic fibrosis-treatment costs $300,000 per year. For better or for worse, companies need to charge that much for orphan disease indications since the patient population is in the thousands and not millions.

Our understanding of human biology has never been greater, but is still incomplete. The reality is that all of this fantastic research is extremely expensive. Given the current reimbursement hurdles, including regulatory approval costs, government pricing limitations, prescribing habits, comparative efficacy concerns, etc., it is extremely challenging to be in the pharmaceutical business right now.

Originally Posted by PharmDstudent

All of the Hep C injectable interferons are requiring insurance PAs. Kinda sucks

yes we require PA

even if we didnt, it would still reject for price override(incivek is like 16 grand a month)

Originally Posted by Redheadedpharm

There is an over-prescribing problem of antibiotics in the United States. We may find ourselves in trouble if there isn't enough new antibiotics in the pipeline to replace the existing ones. Look at azithromycin as an example. Every Joe and Jane that goes to their doctor or urgent care with the sniffles gets a Z-Pak. What happens when that medication doesn't work anymore?

Research is down for big pharma but the landscape of drug development is changing. Now you see more pharmaceutical companies partnering with a biotech company for research and development. This allows the pharmaceutical company to focus more on safety, approval, and marketing and leaves the research and development aspect to the biotech company. I think you'll see a lot more partnership agreements between different companies for the purpose of drug developments in the future.

And don't underestimate the regulatory impact on drug development. Some of the most promising new frontiers of medicine including stem cell research and gene therapy are all dependent on a favorable regulatory environment. We haven't scratched the surface of what is possible in the field of medicine and now that the genetic code has been cracked, the sky is the limit.

Interesting to see big pharma buying a biotech startup to market new drugs these days (Eli Lilly and Avid). Still have doubts on how new research can translate to new medicine...gene therapy and stem cell research still has not made a lot of noise after all these years of promise...more like empty promises to me. I don't blame FDA for being so strict...have to make sure it works, first and foremost.

Originally Posted by notafraid87

Interesting to see big pharma buying a biotech startup to market new drugs these days (Eli Lilly and Avid). Still have doubts on how new research can translate to new medicine...gene therapy and stem cell research still has not made a lot of noise after all these years of promise...more like empty promises to me. I don't blame FDA for being so strict...have to make sure it works, first and foremost.

Not real current on any of it, but tech isn't there yet from what I heard in undergrad. As I recall, gene therapy cured something like 7/10 kids with SCID but 3/10 got leukemia back in the early 2000s. Ever since that, everyone has been kinda restricted on gene therapy. Gene splicing is still too stochastic.

Originally Posted by gadlo

The biggest example of a cautious FDA is the amount of time a drug/product spends under regulatory review.

Drugs don't actually spend much time at all under regulatory review (thanks to PDUFA). After an NDA is submitted a review is completed in around 9 months.

Originally Posted by gadlo

In 1962, a drug spent less than one year from the investigational new drug application (IND) to approval. In 1998, it was over seven years.

The Kefauver-Harris Amendment to the FD&C Act was passed in 1962, which required evidence of efficacy. Prior to that, drugs were on the market with little or no evidence that they were effective. Sure, in 1962 drugs were approved far more quickly; however, at least now we know they work for the approved indication(s). That's certainly worth the wait.

Overall, I agree with you. The pharmaceutical industry is in a tough spot.

Full disclosure: I work at FDA/CDER.

Originally Posted by Brock Landers

Drugs don't actually spend much time at all under regulatory review (thanks to PDUFA). After an NDA is submitted a review is completed in around 9 months.



The Kefauver-Harris Amendment to the FD&C Act was passed in 1962, which required evidence of efficacy. Prior to that, drugs were on the market with little or no evidence that they were effective. Sure, in 1962 drugs were approved far more quickly; however, at least now we know they work for the approved indication(s). That's certainly worth the wait.

Overall, I agree with you. The pharmaceutical industry is in a tough spot.

Full disclosure: I work at FDA/CDER.

Cool!

I think that a better metric for gauging overall time to approval, and whether it is too long or not, is from when a company applies for an Investigational New Drug application. This would take into account all clinical phases and for performing multiple, really long clinical trials with tons of patients, often at the behest of the FDA. Companies respond to regulatory pressures. If the FDA becomes very cautious, the company will respond likely by not even applying for a New Drug Application until they are absolutely confident with the evidence supporting their drug. Only looking at the time after an NDA was submitted would therefore be skewed data.

Some people argue that the FDA should only look at safety and not efficacy. Undoubtedly, it costs an enormous amount of money to get a drug to the market. Many great ideas, with potential clinical benefit, are not even being pursued because of the economic realities that I've mentioned. Given that roughly 10-15% of total healthcare spending is on medications, if companies could more easily and quickly recoup their investment costs, this would greatly decrease the price of drugs. An argument against that position would be that drugs have side-effects, cause adverse events, and can even kill people. If they do not provide a clear medical benefit, then the risk should not be tolerated. However, many drugs are found to not be effective even after they are on the market, so would there be a big difference? I don't know. Additionally, there is significant unmet pharmacotherapeutic need in many indications. For instance, many large drug companies have abandoned their CNS drug research because of difficulty (that pesky placebo effect and spectrum disorders) and a crowded market place. Yet there are many treatment-resistant patients. Would those patients tolerate the risk of a drug with unproven efficacy? Perhaps. Presumably, if the drug didn't work, people would stop taking it, the market would correct itself, and science would be advanced. If society wants more drugs, then perhaps we need to consider taking on more of the risks required for finding new drugs.

So in response to your statement, I don't know if it is worth the wait and the corresponding cost. Fortunately, I am a healthy, young-ish man, and I do not need to make those type of hard decisions. I'd imagine that some people with illnesses that significantly reduce their quality of life or with life-threatening illnesses may say that it is not worth the wait or the cost, that having more therapeutic options at a lower cost would be worth the risk.

Originally Posted by gadlo

The pipeline isn't dry because of the lack of good ideas. The pipeline is dry because we have a lot of good drugs for the major indications (that means no more blockbusters), the cost of getting a drug to market is in the billions, the FDA is very cautious (and this means $ in lost time, more, and longer tests and trials), reimbursement hurdles, government intervention, incomplete understanding of the biology and toxicology, etc. We still have tons of great ideas, but it is too costly for companies to pursue many of them relative to the risks and predicted returns.

Please forgive my momentary, internet hyperbole. The FDA is not insane. The FDA has become very cautious in many indications. Getting a drug through is very difficult. Aspirin would probably not get through this current regulatory environment. The biggest example of a cautious FDA is the amount of time a drug/product spends under regulatory review. In 1962, a drug spent less than one year from the investigational new drug application (IND) to approval. In 1998, it was over seven years. The number of clinical trials required has become greater and the number of patients required per trial is larger. All of this means money. The cost of bringing a drug to market is $1.3 billion. But consider that most companies have more misses than hits. If you count the costs of pursuing drugs which don't receive approval under the total costs, that amount goes up to around $4 billion (http://www.forbes.com/sites/matthewh...ing-new-drugs/). Why would anyone spend that kind of money for their drug to not be prescribed because there are 20 generics for that same indication? That is why we are seeing so much focus on orphan diseases. That new drug kalydeco for cystic fibrosis-treatment costs $300,000 per year. For better or for worse, companies need to charge that much for orphan disease indications since the patient population is in the thousands and not millions.

Our understanding of human biology has never been greater, but is still incomplete. The reality is that all of this fantastic research is extremely expensive. Given the current reimbursement hurdles, including regulatory approval costs, government pricing limitations, prescribing habits, comparative efficacy concerns, etc., it is extremely challenging to be in the pharmaceutical business right now.

Also remember that the FDA was relatively lax at the turn of the century. It's why you saw a lot of copy-cat drugs suddenly appear or that a drug to go off patent would suddenly show up in a "new" formulation. You don't really see that anymore, at least to the extent that you used to.

I think the whole Vioxx withdrawal, in addition to the crap Purdue pulled with Oxycontin, that lead the FDA to really wake up and actually start doing the job.

I don't think our generation will ever see a name branded blockbuster drug like you saw ten years ago.

Originally Posted by phathead

I don't think our generation will ever see a name branded blockbuster drug like you saw ten years ago.

Qnexa is suppose to come out in july I think but then again, I forget

Originally Posted by joetrisman

Qnexa is suppose to come out in july I think but then again, I forget

I'm excited for that one.

So you'll be thin and dumb from the CNS effects of the topiramate

I think that makes you a celebrity... but I'm not sure.

Originally Posted by gadlo

I think that a better metric for gauging overall time to approval, and whether it is too long or not, is from when a company applies for an Investigational New Drug application. This would take into account all clinical phases and for performing multiple, really long clinical trials with tons of patients, often at the behest of the FDA. Companies respond to regulatory pressures. If the FDA becomes very cautious, the company will respond likely by not even applying for a New Drug Application until they are absolutely confident with the evidence supporting their drug. Only looking at the time after an NDA was submitted would therefore be skewed data.

Nice post. I agree, though my comment was directed toward your original post which referred to the time of regulatory review. This period would generally be considered post-NDA.

Keep in mind that "long clinical trials with tons of patients" are not requested arbitrarily by FDA. Such a trial would be required only if necessary to definitively establish a favorable benefit-risk ratio and sample size would be carefully considered in such a case.

Originally Posted by gadlo

Some people argue that the FDA should only look at safety and not efficacy.

To borrow a word you used previously in this thread: insane. This is going backwards 50 years. In this situation, a company could get any "safe" drug approved...and market it for the treatment of cancer. Or migraines. Or BPH. Literally anything.

With regards to Oxycontin, FDA/DEA forced the reformulation for the drug to remain on the market. Oxycontin will still go generic, again, permanently, next year. The reformulation did not impact its patent expiration date.

Originally Posted by Brock Landers

To borrow a word you used previously in this thread: insane. This is going backwards 50 years. In this situation, a company could get any "safe" drug approved...and market it for the treatment of cancer. Or migraines. Or BPH. Literally anything.

Dr. Andrew von Eschenbach, the FDA commissioner from 2006-2009, does not think that limiting FDA to only evaluate safety before allowing marketing is an insane idea, he proposes such an idea in the editorial entitled "Medical Innovation: How the U.S. Can Retain Its Lead-The FDA should approve drugs based on safety and leave efficacy testing for post-market studies" (http://online.wsj.com/article/SB1000...googlenews_wsj). The link is limited to WSJ subscribers, but his opinion created lots of discussion elsewhere.

Like I mentioned, a serious consequence of such an action would be that people may take drugs, with their side effects and possibility of causing adverse events/death, without having a clear medical benefit. This is a serious concern. But we must consider who would likely tolerate such risk. For someone who has a common illness with many therapeutic options and is responding to their current treatment, they likely would not try some new, unproven drug. Likely, those who would tolerate such risk have no other options. They may have an illness with no proven treatments. They may not respond to the treatments available. Indeed, this is already occuring with some off-label prescriptions, and even with drugs that have not been approved for human use.

Just consider that last point about not having any other options. If you had Lou Gherig's disease, and were going to suffer for years from this disease that would assuredly kill you, would trying an unproven drug be insane? People are doing this. I first heard about this in the article "Frustate ALS patients concoct their own drug" (http://online.wsj.com/article/SB1000...943484054.html). Is this insane?

Originally Posted by gadlo

Dr. Andrew von Eschenbach, the FDA commissioner from 2006-2009, does not think that limiting FDA to only evaluate safety before allowing marketing is an insane idea, he proposes such an idea in the editorial entitled "Medical Innovation: How the U.S. Can Retain Its Lead-The FDA should approve drugs based on safety and leave efficacy testing for post-market studies" (http://online.wsj.com/article/SB1000...googlenews_wsj). The link is limited to WSJ subscribers, but his opinion created lots of discussion elsewhere.

Like I mentioned, a serious consequence of such an action would be that people may take drugs, with their side effects and possibility of causing adverse events/death, without having a clear medical benefit. This is a serious concern. But we must consider who would likely tolerate such risk. For someone who has a common illness with many therapeutic options and is responding to their current treatment, they likely would not try some new, unproven drug. Likely, those who would tolerate such risk have no other options. They may have an illness with no proven treatments. They may not respond to the treatments available. Indeed, this is already occuring with some off-label prescriptions, and even with drugs that have not been approved for human use.

Just consider that last point about not having any other options. If you had Lou Gherig's disease, and were going to suffer for years from this disease that would assuredly kill you, would trying an unproven drug be insane? People are doing this. I first heard about this in the article "Frustate ALS patients concoct their own drug" (http://online.wsj.com/article/SB1000...943484054.html). Is this insane?

The article for non-subscribers: https://www.google.com/#hl=en&output...90b5a8625b1eb2

FYI for those who don't have a WSJ subscription, if you google the title and enter the website from google, you will (80% of the time) get the full version. nifty trick!

Ever heard of thalidomide? Thalidomide is why proof of efficacy is required and sulfa elixir is why proof of safety is required. We do not want history to repeat itself.