Minimal number of approved drugs; fewer approved each year

Some numbers that I heard at Harvard Medical School:

  • About 1500 compounds that are currently approved as patented or generic drugs.
  • About 500 in clinical trials.
  • About 10 approved every year and declining.

Declining? With half of the new glass towers in Boston and Cambridge packed with biologists and chemists? “It’s getting tougher to approve new drugs because they have to be safe, be effective, and be somehow better for an average population of patients than current drugs,” said my source. “Don’t get me started on the FDA. These criteria are probably too strict. A compound that has bad side effects for one person might affect another person very differently. So it would be good to have more options, especially for those with unusual genetics.”

27 thoughts on “Minimal number of approved drugs; fewer approved each year

  1. That’s a surprise to me. I would have guessed at least 30-50 new drugs approved each year, and *rising*. Whatever happened to solving the protein folding problem from first principles with supercomputers and using that to advance drug design?

    On the other hand, the relatively small numbers have to make it a little easier to handicap the performance of pharmaceutical stocks. 500 compounds in clinical trial isn’t all that many for an analyst to keep track of.

  2. Clearly law of diminishing returns strikes again. Looks like modern drug discovery process had been skimmed. Time for new innovations which usually come from unexpected places.

  3. Nevermind. I decided to ask Derek Lowe about the protein folding problem and I’m waiting for him to stop laughing before he answers, assuming he does.

    • This is offset a little – a very little – by multiple indications. Most biologics and a few small molecules target multiple diseases. Or at least multiple variants of similar diseases.

    • Sorry that was intended to be a general comment not a reply. As yet there is no approved treatment for fat fingers.

  4. Definitely worth reading Derek Lowe’s blog if you’re curious about this. Having followed it for a few years, I honestly don’t understand how anybody in the medical chemistry field gets out of bed in the morning. The odds of your drug making it to market are right up there with winning the lottery. But entering the lottery is far cheaper, vs. $10-100M down the drain in clinical trial costs.

    Lowe himself is a good example. Highly respected PhD, working in the field for decades, he has yet to have any of his efforts reach the market.

  5. I feel like ethicists are somehow the problem behind this, they are like “human resources” at corporations, i.e., the very last people you want getting anywhere near any real human beings.

  6. 1) it’s not clear that FDA drug approval numbers are declining. Last year 59 agents were granted approval, the highest number on record. See

    2) the number of drug approvals each year is a terrible metric of the FDA’s effectiveness. Me-too drugs in existing classes are rarely better than the first in class.

    Increasing numbers of drugs, particularly in oncology, are being approved on the basis of poorly conducted trials, sometimes even without controls – see dabrafenib–trametinib. More still are being approved on the basis of improvement in progression free survival without evidence of improvement in overall survival. See the work of Vinay Prasad, eg

    The bar for approval has already been substantially lowered. The major beneficiary is the pharmaceutical industry.

  7. Isn’t this akin to the current Boeing self-regulation fiasco? You have the foxes guarding the hen house. Inevitably, the drug companies, who are in the best position to test their own drugs, become compromised by money and act immorally. The list of botched or falsified testing resulting in dangerous drugs getting to market seems unacceptably high. The FDA, in turn, ramps up scrutiny because of industry corruption and compromise. This is why we can’t have nice things. Capitalism corrupts absolutely. The Oxycontin saga alone is mind blowing.

    • You are right Senorpablo, Communism is an ideology professed by real-world socialists, GULAG was a socialist enterprise of course as USSR was socialist and wanted to attain communism. Your per million population graph has many capitalists countries, with US being only large country on the list. Top country Switzerland is more capitalistic than US with very low federal tax and no inheritance tax. If you are about # 3 Sweden then they are capitalists and have been dismantling their welfare state for a while now (Sweden abolished inheritance tax in 2005). Only very small country Norway (#5) is expropriating and re-distributing significant % of their citizens’ income but even they have absolute private property rights and abolished (small to begin with) inheritance tax in 2014, and can afford their antics because of their small population and very large (capitalist) sovereign fund that is fueled by light carbohydrates that emit CO2, due to luck of their location. Talking about real drugs, large Swiss, British and German pharma companies all have very large representation states-side, including R&D and manufacturing. No Vietnam, Cuba, Venezuela or even powerhouse China with de-facto capitalist economy on per – million people list.

    • Anonymous, you’re inventing your own criteria to define socialism. Tax rates? Not only do many of the countries on that list do medicine better(contrary to your original assertion), they have universal/socialized healthcare–which according to the right wing, might as well be communism. And, they do it for cheaper with better outcomes. No, capitalism isn’t the best at everything. Though, it’s fantastic if you want to maximize wealth inequality and wage stagnation for 95% of the population. It’s the closest thing to perfect at allowing 1-5% of the population to soak the other 95-99%. Our healthcare system, including pharma, is a testament to that. And the highest incarceration rates of any industrialized nation.

    • Senorpablo- The US Health Care system may have some artifacts of capitalism but is far from free-market. I would say it is more ‘socialist’ than not.

    • Senorpablo, as in all of the countries on the list, US healthcare system has been serving poor for free but up to Obamacare had lesser waiting times. All countries including US have capitalistic for profit component, with many treatments available only in US, some – only in Switzerland. I mentioned inheritance tax because it expropriates property to pass on, unlike payroll taxes. Together with large property taxes (people complained on this blog that they have to sell their inherited Manhattan houses not being able to afford real-state tax) and a-la fascist non-owner control of property it could be a closest measure of socialism in modern capitalist society. It is treasure made by capitalism that allows poor treated for free in US and other remaining mostly capitalist countries. Definition of socialism: “Socialism is a range of economic and social systems characterised by social ownership of the means of production and workers’ self-management, as well as the political theories and movements associated with them. Social ownership can be public, collective or cooperative ownership, or citizen ownership of equity “

    • Anonymous, You’re greatly understating how noncompetitive American healthcare is. Costs more, worse outcomes. It’s one of, if not the most free market systems on that list of countries that do better at medical, is it not? You throw up, as is typical among right wingers, meaningless and ambiguous metrics such as “wait times.” Wait times are already baked into the outcomes, are they not? All those countries have wait times, yet they still have better outcomes. It’s a right wing boogeyman.

      Perhaps you should consider why it is that people can’t pay taxes on their inheritance? Hint: extremes of income and wealth inequality. As a society, money gets taxed any time it changes hands. Why should offspring of estates over $5.5 mil be entitled to special treatment? Oh, the horror that people can’t hang onto their Manhattan condo’s. Would they even be able to pay the property taxes if they can’t swing the inheritance tax? Aren’t all of the “mechanisms of production” in the US privately owned? No citizen gets shares of stock as a birthright. Private individuals and companies purchase stock. And, they enjoy lower tax rates on any gains than typical working stiffs pay on wages. Our society is rigged. It is not socialist, it is capitalist advantaged. How is it that all the gains in productivity of the last 40 years have gone to the top 2%? And, why is that trend is accelerating? When the house or a player consistently wins at gambling over a long period of time, someone is advantaged. Our society is advantaged to the top 2%. It’s born out over the trends and outcomes of the last 40 years. Those 2% of people are not working orders of magnitude harder, nor have they suddenly become orders of magnitude smarter.

      To tie this back to the original post, a select few in the healthcare industry, Dr’s and execs at insurance, pharma and hospitals are making out like bandits at the expense of society at large. It’s a form of extortion–survival is human nature and people are ripe to be taken advantage of in its pursuit. I expect that all of the countries that have better heath outcomes also pay their health professionals substantially less. That’s a product of more socialist societies that prioritize things other than profits, such as well being, above all. At the end of the day, free market, capitalist societies like ours, boil down to the gamification of manipulating and taking advantage of human nature.

    • Senorpablo, you keep referring to mythical outcomes. Outcomes are clear when all pre-conditions can be controlled and enumerated. So pick recent Finnish immigrants in US and compare their medical procedures outcomes in US with same medical procedures outcomes in Finland. Wait time are reals, in many cases they increased x4 since Obamacare.
      Luck of competition is a trait of socialist and controlled economies. Sorry that we have it now, this is recent development. Had to follow a person to one of the top US hospitals that I also observed 7 years ago, it used to be exemplary. Now there patients are sleeping in the halls and doorways. This is clear degradation of medical services since Obamacare was passed.
      So for you and “people”‘s happiness doctors should work for free or for peanuts? Try to get put them through medical school than.
      Sorry I did not get what you were trying to say on real estate and inheritance task. Were you trying to say that people need to work hard just to keep their paid property? I.e you think that you and others have ownership of others people lives, they have to spend their time, efforts and change their wants to provide you with free services?

    • Anonymous, you don’t need to have controls when referring to the medical outcomes. You’re promoting how much better healthcare is in a capitalist system vs a socialist one. Again, it’s all baked in. It’s much more efficient to not hit yourself in the head with a hammer than to be the best at repairing hammer blows to the head, aye? In a capitalist system, you get Dr’s and hospitals, drug companies who are focused on profits. Whereas perhaps the rest of the world, where Dr’s are paid less than the US(not for free as you suggest), you get people going into the professional and focusing on doing the job rather than maximizing profits. Likewise, in a capitalist system, you’ve got massive companies, farms, supermarkets and restaurants serving up unhealthy food which inevitably drives down our collective health. The difference in peoples overall health is visually and immediately apparent when you go to Europe or Australia for example. Their systems aren’t built around the notion that the masses are turnips which to be squeezed for personal profit, regardless of the larger societal implications. Capitalism doesn’t allow for that any longer. It’s a runaway train where decades of gamification have eroded any remaining scruples when it comes to taking advantage of your fellow human for your own gain.

      What’s a reasonable explanation for the accelerating income inequality of the last 40 years? 2% of people are getting smarter while the rest of us get dumber–what’s caused that change? Or, is it that our capitalism is becoming more efficient, and we’re finally casting off all the socialist encumbrances to the top earners so that they are just now are starting to reach their true potential?

    • Senorpablo, your love for profits is just a human trait for love of good life and present under socialism. What is absent under socialism is insensitive to work, interest in final result and choice of products. And good luck bringing pharma maker to justice for malpractice under socialism when public / trade union (read: nobody, formally state) owns it. Economic system has nothing to do with personal choices or justice. US is full of partnership businesses who if successful and grow beyond simple cooperation and change their structure to more centric ownership. Your narrative that top 2% are getting “smarter” whatever it means (I assume richer) is false. Yet US has one of the highest upward social mobility rates in the world.

  8. Can someone on here please explain to me how fast diseases are growing? do we get a new strain of indigestion or headache every year, that gets added to the rest?

    We have a treatment for most, if not all, diseases. Some are extremely effective, some are less so. Let’s keep in mind most people can, with a modicum of care, get themselves well past 80 in pretty good conditions. So, new drugs are:

    1) an attempt to improve on drugs that are only partially effective, in the hope that something more effective can be found either for the general population, or for an identifiable subset of the population. A new drug that is more effective than what we have in some people but has unacceptable side effects for others (in a way we cannot effectively predict) is not going anywhere. There are valid ethical concerns for that — volunteer yourselves and your kids to frug testing and prove me wrong.
    2) a desperate attempt to replace a perfectly effective drug that is going to be soon grandfathered as a generic, and thus become far less lucrative.

    Get a mighty grip on reality folks. The number of new drugs is guaranteed to whittle down to a trickle for perfectly understood, benign and banal reasons.

    • > Can someone on here please explain to me how fast diseases are growing?

      The western world of the era 700 – 2000 AD is coming to an abrupt end due to pervasive and profound mental illness. It will be gone within the lifetime of people reading this blog. I’d call that pretty fast.

    • Lord Palmerston, I understood we are talking about diseases, not issues that magically only affect people with US citizenship.

    • > I understood…

      Frederico, I’m afraid not. But then, the circumstances on which I commented would entail that many would not be able or willing to understand.

    • Lord Palmerston, the tedious attempt to inject politics in a technical issue is, well, tedious. Good try, no cigar.

  9. Derek Lowe was nice enough to respond to my wet-behind-the-ears layman question about the Protein Folding Problem and supercomputers (particularly IBM Blue Gene and Blue Gene/L) vis-à-vis drug design. He sent the following answer, which I think is quite good and a great starting point for anyone who wants to learn more.

    What a pleasure to talk with him! Thank you, Dr. Lowe, and I appreciate your sense of humor!

    I’ll post his entire reply. He also invited me to write back if I had more questions. What a great guy:
    That’s not as dim a question as you’re thinking it is! One part of the answer is that IBM was hyping their own prowess and the impact of protein structure in general. There’s not going to be a single solution for protein folding, that’s for sure, unless it’s something like a complete understanding of hydrogen bonds, solvation, entropic factors, pi-pi interactions, and all the rest of the things that go into protein structure. (So if that counts as a “single solution”. . .!)

    And IBM wasn’t going to solve it, either. This is not a field that is going to be settled by throwing more computational power at it, because what’s needed are better insights into the physical phenomena themselves. There was recently a protein-folding competition (held every two years) that Google did really well at, and that unleashed some pretty wild-eyed stuff too, about how they were about to make big breakthroughs, what those would mean for biology and drug discovery, and so on. Very similar to the noise around the IBM stuff, and it’s subject to the same objections.

    Knowing more protein structures, and being able to predict them in advance, would certainly be a good thing. But it wouldn’t solve the bottlenecks of drug development, which are connecting proteins (and more accurately, protein pathways) to disease, and connecting them to off-target toxicities. The 90% clinical failure rate is almost entirely due to breakdowns in those areas: Phase II trials failing because the target turned out to be the wrong one or not as important as we thought, and Phase III failures because some nasty side effect emerged. And the only cure for those is knowing more about human biology. Expecting protein structure to solve those is way too reductionist, and I speak as someone who’s fine with reductionism. But you still see people going for that line of thought. Generally, though, the more experience they have with actual drug development, the less likely they are to buy into that pitch (!)
    Lowe is in industry, but I think he’d also do very well in academia if he ever wanted to let the undergraduate students empty the sand bucket. Just so long as he remains the official gatekeeper of the chlorine triflouride, lol. It sets sand on fire!

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