With no prospects for profits, big pharma neglects new infectious diseases
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Basically, rather than paying for drugs on a per unit basis, you pay a lump sum for access to the drug. This solves the issues of spending $100M to develop a new treatment for some disease where there is never a outbreak and you cover none of the cost of R&D.
There have been ideas to have X-Prizes for new antibiotics. Discover a new drug for a anti-biotic resistant infection? Great, here is $500M as long as you agree to produce as much drug as needed for free or some nominal cost.
Why not give $5bn (or whatever the NPV of the drug at a reasonable rate of return might be) in exchange for releasing the drug into the public domain? Then any number of generics manufacturers could be contracted to maintain a stockpile.
> for biologics, "the product is the process."
[0]: https://archive.bio.org/articles/how-do-drugs-and-biologics-...
(Source: a colleague from another country where the manufacturer also made the drug unavailable asked to have the drugs procured from India)
Edit: the drug was Nexavar by Bayer. The CEO was quoted as saying "No, because we did not develop this product for the Indian market, let’s be honest. We developed this product for Western patients who can afford this product, quite honestly". Recently it seems the Indian courts also allowed export licenses for the drug to other markets where Bayer similarly refused to launch - sadly after the relative of my colleague passed away - at least partially from the delay in procuring the drug.
Then the original developer can be the manufacturer. But no need to add hurdles.
Hmm... a system where uncommon but extreme spikes in the cost of care are artificially distributed so that an entire society can bear them as a group... that sounds oddly familiar...
And at any rate, the alternative is what we have now - no drugs to treat these diseases.
As an aside, the "netflix model" for drug payments is already a reality in Louisiana. Basically the drug maker and state government negotiated a payment for enough hepatitis C drugs to cure everyone in the state.[1]
Only Medicaid + inmates, not everyone in the state?
Jokes aside - while people are justifiably pointing out the community healthcare angle, arguably this problem is exacerbated by the American FDA drug approval model, ie no corporation will fund clinical trials unless they're guaranteed a profit monopoly.
The idea is that big pharma companies have to publicly post a price for each of their patents. If anyone is prepared to pay that price they get the patent for that price. Next there needs to be a tax that is a percentage of the price of the patent. The money that comes from this tax needs to be funneled back into healthcare or even better go straight to the ones who are paying for the particular medicine that the patent protects.
Now the level of innovation can be set by how high the percentage of the tax is. If the tax is very low healthcare will be expensive but there can be lots of innovation. If the tax is high healthcare costs will be low but one can also not expect much innovation.
Of course, there also are some other things that need to be fixed. E.g., doctors should not get all of their schooling financed by pharma companies and so on.
The general idea of such taxes could be applicable to any sort of non-replacable entity, e.g., it could also apply to land. For one thing, this would make feudalism regarding land quite impossible, which would generally be considered a good thing.
My main issue with it is risk or noise. It's not clear how we avoid a bunch of over optimistic actors from "winning" the patent based on wrong estimates and then themselves going broke. Sure, if one or two firms get in trouble they can sell the patent, but what stops a succession of overly optimistic people from holding it to the detriment of everyone? The person who bids highest at an auction could well be the person with the most wrong inputs to his model.
Kinda like how there's this one building in my town that several restaurants have tried and failed in, but as a monopoly.
I like the idea for land rights though. Those are not gonna hold back all of society if a bunch of people do badly at it.
Tax money is allocated for one thing is often used for other things. There is nothing preventing lawmakers from doing this, they after all, make the laws.
Every single major pharmacy company is actively developing treatments And doing clinical trials where they are in sharp competition and don’t have a monopoly. Obvious example that’s always picked up in US is diabetes. No one has a monopoly on insulin or insulin analogies and you have several corporations constantly competing and innovating improving the treatments.
The reasons for lack of development in some areas is not risk aversion from the pharma companies, it’s just that there simply isn’t a business case for investing there as oppose to other areas in the current setup.
There are a lot of businesses I'd happily set up if I knew I'd have limited to no competition. When competition is more fierce, it disincentivizes me to even try.
If I was guaranteed the lionshare of say, local coffee goers across a large area and didn't have to worry about Starbucks, Peet's, etc. I'm pretty sure I could make it successful and my life would be pretty easy, all things considered.
A lot of rural ISPs can operate this way because it's not viable to compete with their infrastructure foothold in a lot of cases and barriers to entry are high/capital intensive (similar to pharma).
I work in a research environment and there are a lot of funding opportunities/solicitations out there that fit our internal capabilities that we don't even bother writing proposals up for because we know how competitive and unlikely it is to be successful compared to certain other opportunities. Instead, we choose our battles where we suspect we have a higher probability of success: less competitive options. This leads to higher ROI for our time. It works fairly well and I imagine most businesses try to operate under a similar perspective (or more dubiously where they also try to actively stifle their competition).
If you were going to develop the drug at your own cost with no subsidy for failure, why settle for 500M? Why not do it on your kwn merit and reap billions instead? And keep all the IP.
A huge amount of their research already is directly responsible for private industry profits; they can be happy with that freebie. But for things like vaccines in emergencies and insulin, if this be socialism; let's make the most of it.
Most AR bacteria can be killed by trying different antibiotics. Sure they can mutate to something more dangerous, but it doesn't make sense to make drugs for bacteria that don't even exist yet. There are too many variables to account for.
We may have a bad “flu” year this year, with a spike of elderly deaths, but we have a bad cancer year every year.
It's not fair to say we don't develop cancer drugs because some, very difficult to treat cancers, haven't seen as much progress as others.
It covered the last 30 years. Each new therapy improved survival by only 6-12 months, but each new drug was more effective than the last. Over those 30 years, the median survival went from 6 months to over 5 years.
People shouldn't discount incremental improvements because that's often how medicine progresses.
Here's another recent success : https://hcp.lutathera.com/ --- https://www.nejm.org/doi/full/10.1056/NEJMoa1607427 At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group.
Lutathera delivers a radioactive molecule to the tumor.
That's what capitalism does to generics.
Daraprim wasn't generic until literally 5 days ago: https://www.biospace.com/article/fda-approves-first-generic-...
There is a lot of significant work happening in infectious diseases. However, curing cancer is the holy grail and a pursuit of that is on the same level as pursuing manned space flight. Flying people into space seemed frivolous at the time as well. After all, think of all of the hungry kids would could feed if we redirected Apollo money! However, space flight gave society countless advances that we didn’t foresee at the time. Perhaps we should argue that studying quantum physics is a waste of resources. Or studying astronomy. Or any number of fields where societally-useful breakthroughs are few and far between.
It’s ridiculous to imply that developing cancer drugs should be ditched in favor of developing more infectious disease drugs. We can walk and chew gum at the same time: this isn’t guns or butter.
If we want to apply pure rationality to drugs: let’s stop cancer drug expenditures so we can save more people from malaria, then we could apply that logic to social programs as well: why bother helping the mentally disabled when instead we could direct those funds towards something that provides more economic value to society? A kid with cerebral palsy isn’t going to contribute as much to society as a healthy kid — so why waste resources on that research? Of course it isn’t a waste when it’s your kid. Following that line of reasoning and we ultimately end up with eugenics and society would become a very nasty place indeed.
But cancer itself is... complicated. There are many different types with many different causes that are complicated by many different things. Breast cancer is not the same as skin cancer, and neither of these are lung cancer.
But we do, to an extent, know how to treat things to a point. Sometimes, our best efforts have only resulted in giving folks 3-6 months.
And we do cure or prevent some infectious disease. The plague and leprosy, for example, is curable. We have taken leaps and bounds with HIV/Aids - while we can't really cure it, we can give drugs to folks to stop it from being so infectious. But like cancer, "infectious disease" comes in many forms, some being vastly more complicated to "cure" than others. This is why some things, like the common cold and common influenza do not have cures. These are hard problems. And for lack of better words, we've simply not "unlocked" the secret in ways that would be good year after year.
And you can construct a "rational" argument for it: the slaves are living under an oppressive government anyway and apparently nobody is going to intervene, so if they're stuck in internment camps, may as well give them something to do with their time. Sure, they don't have freedom, but they weren't going to have it anyway, so it's still rational. Right?
In seriousness - if you don't take into account the economic reliance on slavery that jurisdictions with legal slavery (e.g., the US South in the 1800s) had, and you claim it's solely that irrational slaveholders saw certain people as less than human in the abstract, you've missed a good part of the explanation and risk inaccurately understanding how to prevent it from happening again. People had a strong economic incentive to come up with justifications for their objectively immoral actions.
Is there a NASA equivalent for infectious diseases to launch a covid-19 moonshot?
It’s short enough that clearly they expect it won’t be very hard, like no one would say a general cure for cancer is 18 months out. So what is preventing us from speeding it up more? Why can’t it be made in 6 months, or 3 months? Is the majority of that 18 months a basic r&d phase of figuring out what will work? If so, why can’t it be parallelized and sped up with more resources? Is it time for clinical trials? To ramp up manufacturing? I can’t help thinking that for a disease that prevents such a big risk to society, there must be clever ways to speed up the normal process for this kind of thing, perhaps with some government involvement in funding or coordinating efforts.
All the things you said are factors. Clinical trials are one of the biggest because you have multiple phases to observe to guarantee safety.
It's no use shipping a vaccine in 3 months after a small test and have everyone die in a year because of a side effect no one waited long enough to see.
Drug development and safety is a very complex space from what I've learned
And safety shouldn't be underestimated. The story of dengue vaccine development is a cautionary tale. The first time you get dengue is usually not too bad, but it can be deadly if you get it again. Part of that is hypothesized to be driven by your own immune system, which, once immunized against one strain, produces antibodies against it in the next infection. However, if it's a slightly different strain of dengue the second time around, the antibodies meant to neutralize the disease are believed to make the disease more virulent instead (antibody-dependent enhancement). The immune system makes it worse. So when a dengue vaccine that didn't fully immunize against all strains was developed (not deliberately, people tried to immunize against all strains but this is a case where less efficacy than expected made things worse), it didn't make things better. It ended up priming people to get dengue.
Biology is super weird - even something as "simple" as vaccine development has a lot of unknown unknowns. And as dengue showed us, it's not just a case of "it might not work," because it could make things worse. That's why we have to run these clinical trials and take time to do things right, especially for something that would be as widely deployed as a coronavirus vaccine.
The NIH and all are likely already researching this strain, and importantly they're also funding labs in universities nationwide (since there's no reason to expect that a team of scientists who come up with the insights needed to find a cure would happen to already work for the government).
The government tends to be really good at getting things with clearly defined goals done, and they're good at rapidly scaling any work that needs massive funding an institutional support. But finding a cure for a viral infection is more of a creative task (and not a task that is important enough to be worth it likely - vaccination and preventative measures are probably more important and more feasible to implement since they don't necessarily require a scientific breakthrough).
And probably worth adding that in public health emergencies, the FDA is more than willing to pull back on regulations in the interest of the public good.
The downside of that is greatly reduced new drug development due to the expense, much more expensive drugs, and years of delay for the ones that are worked on. If you have a less popular disease, or can't wait years, you're out of luck.
https://www.fda.gov/about-fda/office-clinical-policy-and-pro...
The FDA has not shown any willingness to pull back on regulations during the current COVID crisis, nor have they historically shown any such willingness. Politicians have forced them to. They have never shown any organic willingness to relax regulations.
Fraud is already illegal. Doctors can already be sued for malpractice. Testing for efficacy makes no sense in a world in which off label prescribing is routine.
> Assessing the FDA via the Anomaly of Off-Label Drug Prescribing —————— ——————
> Once a drug has been approved for some use, the FDA has almost no control over how that drug is actually prescribed. The prescribing of drugs for non-FDA-approved uses, called “off-label prescribing,” is widespread. Drugs prescribed off-label have not met the FDA’s requirements for proving efficacy in the off-label applications. The practice of off-label prescribing therefore raises interesting questions. Why does the FDA, in effect, require that some drugs be tested for efficacy but not others? If there are good reasons for the FDA to have strong pre-approval powers regarding efficacy, shouldn’t FDA post-approval powers be commensurate? Alternatively, if there is good reason for widespread off-label prescribing, doesn’t this call into question the FDA’s pre-approval powers?
https://www.independent.org/publications/tir/article.asp?id=...
> There are also scientific reasons to replace Phase 3. The reasoning behind the Phase 3 requirement — that the average efficacy of a drug is relevant to an individual patient — flies in the face of what we now know about drug responsiveness. Very few drugs are effective in all individuals. In fact, most are not effective in large portions of the population, for reasons that we are just beginning to understand.
> It’s much easier to get approval for drugs that are marginally effective in, say, half the population than drugs that are very effective in a small fraction of patients. This statistical barrier discourages the pharmaceutical industry from even beginning to attack diseases, such as Parkinson’s, that are likely to have several subtypes, each of which may respond to a different drug. These drugs are the underappreciated casualties of the Phase 3 requirement; they will never be developed because the risk of failure at Phase 3 is simply too great.
http://www.washingtonpost.com/wp-dyn/articles/A43257-2003Nov...
Phase 3s already are no longer required, it looks like the article you linked was written in 2003? That was literally almost 17 years ago when we'd just barely sequenced the first human genome. There are entire fields of medicine - precision medicine - that literally address the whole subgroup question. Companion diagnostics are routine, rare disease approvals are up, plenty of Huntington trials in progress - that article might as well be about an alien civilization with how different things are today. Value based pricing, redefining cancer into separate genetically defined baubgroups and developing drugs for each, Gene therapy, ... It's no longer easier to get approval of a drug that's marginally successful in a large population, smaller populations with large effects make it way easier to see responses. And the 21st century cures act in 2016 evolved the regulatory landscape even more - it's like comparing Sputnik with the ISS. Yeah, they're both sattelites, but the field has come a long way in the time between the two.
The key with those is that high pricing let's those rare disease drugs be blockbusters - you can still make enough money in a disease with only a few thousand patients in the US if you're able to charge whatever you want.
We've seen less interest in drugs that can't be blockbusters because the costs have gone up, yes, but we also haven't had another thalidomide yet
[1] One example of this is dietary treatments for disorders. It is very difficult for these to become standard of practice, because no company will want to fork over the $$$ to do a clinical trial to prove that a specific dietary intervention improves outcomes. When after its all done people can just do the intervention on their own and not pay the company money. This biases treatment towards pills that can be prescribed and patented.
Earlier I said think of the thousands of lost lives, but it might truthfully be millions considering the damage caused by type II diabetes which pharmacological interventions are relatively impotent to treat.
I recall approval for some diet drugs was removed because they were causing fatal heart attacks. I recall recently some cholesterol drugs were causing unanticipated problems, too. Tylenol is now known for causing liver problems, even failure.
Exactly this is why the motivation to do at least some things should not be bound to earning profit.
There is common goods that we need to share, global issues that need to be addressed together and we need to find ways to achieve this if we want to develop further as a civilization.
Money must not be the sole reason why we do things or we will fail with this "strategy" and we need to come up with good ideas for an alternative and try it.
I know this will probably not make me very popular especially with people living in the US as their minds are constantly being flooded with the idea that everything straying from capitalism is socialism and therefor evil. I will post it nevertheless, down-votes don't hurt and I will write my opinion until it is censored completely.
Here (https://github.com/bionicles/coronavirus) is code to design CRISPR-Cas13 CARVER (https://www.sciencedirect.com/science/article/pii/S109727651...) 30mer guides against regions of Coronavirus conserved between SARS, MERS, HKU1, and SARS-nCoV-2 (Covid-19 Virus) and not found in highly expressed Lung protein-coding RNA. Uses BioPython, Redis SADD/SISMEMBER, and tools from EMBL (Emboss Consensus and Clustal Omega Alignment) and data from NCBI. The good news is, it's probably possible to delete Coronavirus genome directly inside the lungs, without vaccines; just deliver nanoparticles or adenovirus (doesn't replicate) with an inhaler and express CRISPR-Cas13 and the gRNA using the Surfactant promoter sequence for lung-only expression of the therapy
disclaimer: I need to work on the readme and write a blog post, but the data is there and the general core works. There's ~30k guides possible and 226 target 13 longest conserved regions across 4 different outbreaks spanning 17 years of virus evolution (provides reasonable confidence these regions are necessary for the virus to function)
If anyone knows some folks in the Pharma / Biotech industry I could use help to run the tests on this, tell em to email bion at bitpharma.com
edit: readme improved. currently looking for promoter consensus sequences for lung (surfactant protein TFs like TTF-1)
What's not rational is cutting funding to supposedly disappeared diseases. They do re-occurr. The Spanish Flu died out at first, only to re-emerge in WW1 trenches and wreck absolute destruction.
Wouldn't the fact that the disease has disappeared in human populations greatly increase the required funding and limit the effectiveness of the research? The best you could do would be to produce a bandwidth of candidate drugs that can't advance to human trials for ethical reasons.
Similar to financial crisis, if the next one could be predicted, it wouldn't happen.
Thats how incentives gets aligned.
https://camelcamelcamel.com/iProven-Thermometer-Temporal-For...
This effort would honestly be better spent working on things humans already have.
Late Stage Capitalism Failure.
No ability to make a bajillion dollars in rent-seeking profit. So F it! Let the people die.
Big capital put this idea inside the heads of many people living in the West and until today they really believe there is countries who are socialist/communist. Neither the GDR nor the UDSSR or China are examples for countries like that and people who know about politics, economy and society know this as a fact.
It is easy for you to criticize all alternatives at once because you have never seen any and chose to believe what the ruling party (=capitalism) makes you believe.
It won't happen because you'll shift the goal posts.
A common dodge is that they're state socialism. The problem with this dodge: it's definitely true that state socialism is impure. But, it's 90% of what you want, and it fails catastrophically. Then the answer is, "well, it can only work if it's 99%!"
The regulated markets we have in Western nations, however, are 90% of an ideal "truly free market" and they work quite well. And we find that incremental reforms that deliver to people a little bit more of their economic liberties also improve people's lives bit by bit. Markets have the property that the freer they are, the more benefits they provide.
The other dodge is that "it wasn't socialism's fault," especially with Venezuela. Yes, they had an economy centered around oil and that was a problem. The issue was that socialist-inspired reforms made it worse, especially nationalizing the oil companies and price controls. Markets thus have an additional property that they are robust, they allow people to route around problems and mitigate them. Planning is brittle because it necessarily centralizes power, and it tends to fail because planners can't respond to crises in a decentralized manner the way a market naturally does.
The third dodge, common now thanks to Sen Sanders, is the Scandanvian nations show that socialism works. But their economies work because they took the opposite approach of 10% socialism. That's not great for apologia since it follows that socialism only works when you hardly do it.
> Big capital put this idea inside the heads of many people living in the West and until today they really believe there is countries who are socialist/communist.
No one who read the dictionary[2] is claiming that there were any communist nations, since a defining aspect of communism is the absence of the state. You can have lots of communists (persons whose end goal is communism) in a socialist nation, of course, since, as Lenin noted, the purpose of socialism is communism.
And Lenin introduced state socialism, not some mad capitalist, and he believed it was, if not proper socialism, a clear stepping stone to socialism. The nations definitely called themselves socialist, and socialists all over the world agreed and while things appeared to be going well, they were bragging about how this proved socialism worked.
But it wasn't working because the planners were lying. Socialists here lied and covered up tremendous deaths[1]. And it's only when the problems couldn't be hidden that they became not socialist anymore.
[1]: https://en.wikipedia.org/wiki/Walter_Duranty#The_Holodomor_(...
[2]: That does leave a lot of people claiming it, of course.
Because those countries are attacked and undermined relentlessly by a much larger nation(s)?
There isn't a single tool to solve every problem. Sometimes you need capitalism, sometimes you need socialism. Countries that are purely capitalistic or purely socialist have failed miserably. The wealthiest and most successful nations on earth have all employed a mix of socialist and capitalist ideas.
The reason for this is FDA is fundamentally extremely conservative. The people that run the regulatory system are just faceless bureaucrats and are risk adverse. Their pay is based on seniority and there isn't any financial motivation for them to take risks or stand out. FDA is nothing more then a collection of individuals so the motivation of the agency is a mirror image of the motivations of the people running it.
To put it bluntly:
When diseases like cancer or influenza or <insert name of any disease> kill people the diseases get blamed. But if a drug makes to it market and ends up maiming people or killing them then the FDA gets blamed.
So from the FDA's perspective it's much more important that we have ultra-safe drugs then it is to have new drugs to cure and treat diseases.
The regulators are going to take the default position that more testing and screening and expenses are good. While allowing consumers and doctors to take risks to treat diseases is bad. And over the decades it has just gotten more and more and more and more expensive to get the drugs out to the public.
And since it's too expensive to make new drug companies because of the regulators then you will never see any smaller nimble companies come in and compete with them and force the big companies to behave themselves.
This is why you see all the generic drugs being bought up in the past couple decades. During the Obama administration they signed regulatory changes that rose the cost of validating generic drugs considerably. It wasn't so expensive that it would drive generics from the market, but it's expensive enough that you can't make new generic drug companies. So the big name brand drug companies just buys them all up. And because of that they no longer face competition from generics. They own both the name brands and the generics.
If it was cheaper to make generic drug companies this approach wouldn't work. People would make new companies for the sole purpose of getting bought. It would make buying companies up to kill competition unsustainable.
I've worked in heavily regulated industries before and it's a pretty obvious pattern. Regulators regulate. Costs go up. Competition goes down. And then the big companies become isolated from competition because it's just too expensive to compete with them. Then the government has to bend over backwards to ensure the profitability of these dominate corporations because if they were to go out of business there would never be any replacements.
It's a form of market lock-in. Over regulation effectively becomes a license for these big pharma companies to do pretty much whatever the fuck they want. They love it.
I don't think we have ultra safe drugs. I could be just paranoid, but I don't think the FDA is that good at monitoring the manufacturing of drugs. And I know I've read about how sometimes they approved a new dosage without actual testing and it turned out in at least one case the delivery mechanics didn't work properly.
Deregulation is like reform. Enough people think it's automatically good, that it's completely meaningless, and because it's meaningless the worst people pick it up as a slogan and run with it.
As someone that could really benefit from new drug approvals, I don't see deregulation as my savior because if it's executed by the worst people, then it will just lead to more snake oil and less ability to differentiate.
Didn't something like this happen with Martin Shkreli? From what I've read, the drug that they upped the price on had its patent expire decades ago. It's just that nobody else was producing the drug, presumably because it wouldn't make enough money. This resulted in essentially one company being the sole source of the drug, not because of patents, but because of cost.
I don’t know anything about the generic drug marketplace. I’d guess the issues are more complicated than what you describe. The FDA’s mandate is safety, not anticompetitive practices.
One surprising takeaway from working with our regulatory consultants is that apparently many actors try to game the crap out of the FDA’s processes. The FDA is really the only wall between shenanigans and consumers.
In 2018 we had an estimated 400k people dying of Malaria [1] & around 600k (est.) people dying of cancer in the US alone. [2] Compare that to the 3110 deaths that have happened in the last 3 or so months for COVID-19. [3]
I think a little perspective would go a long way here.
[1] https://www.who.int/news-room/feature-stories/detail/world-m...
[2] https://www.cancer.org/research/cancer-facts-statistics/all-...
[3] https://www.who.int/dg/speeches/detail/who-director-general-...
There were 300 deaths 30 days ago. There will be 30,000 this month. And the month after that?