It doesn't make for a very compelling news story, but the real reason why Glybera failed is because it's not that great of a drug and it loses effect over time and you can't redose with the same AAV vector. They also relied a surrogate endpoint versus actual clinical measures (as those were to confounded by the small sample size and patient variability).
It just barely got approved by the EMA and based on feedback the company didn't bother to pursue FDA approval.
Everyone is blaming the company or the patent system or general greed, but really there is an extremely simple solution: pay the $1M. In Canada and Europe it's medicare, ie taxes, ie the general population that would pay for it, but they refused. In the US it's insurance companies, ie the general population (as insurance is just socialized losses), that refused. If people are uninsured then force the state, ie everyone who is feeling so bad about it, to pay for it. It's odd that being the genius inventors also means that you now also have to be the only ones to pay for it. This isn't a story of exorbitant profits - even at a million a dose they would barely make their money back. It makes no sense to isolate the group of people who are actually working on the thing to be the only ones to pay for it.
By extension, this story demonstrates how we price life. What if the cure was a billion dollars, is that worth society paying? What about a trillion? At one point a limit is reached, and it seems that one million is one of those limits that we all quietly agree upon.
I can’t imagine how hard it must be for the dozens of people out there suffering from this rare ailment knowing a perfect cure/treatment is possible but not worth it for the shareholders.
We as a society kind of do this all the time. We bail out the banks with billions, then let some poor people starve. Also in the general case, I'm quite surprised that people don't get fed up with the government acting against their interests.
Since it's a one time cure, I think the 1mio price was reasonable. At least compared to 10+ multiple day hospital visits. This was just the government fudging their negotiation.
The shareholders are doing as much as the rest of us to help those dozens of people. It isn't fair to cast the blame on them.
The real culprit here is the system of laws and controls that forbid anyone else from stepping in to fill the hole they've left. The regulations and regulators deserve to be held up as the problem here. If it wasn't illegal to compete then maybe someone would. Maybe even one of the people who need the drug.
Isn't there an argument where humans arnt' here just to be fleeced? I mean who came first ? the chicken or the egg, are we just creating the monster that'll devour us? In a twisted way the profit motive basically is anti ecological, after all people talk about shareholders but they're just some pension fund who won't be around when we're under water.... I realise capitalism helps us find the most efficient solutions, but at one point we're the ones being milked (to death) and some big cheese(Welch GE) finds a way to create wealth by creating debt and then 20 years later they split it up to create more bubble wealth it becomes ridiculous and you're throwing the baby (us) away with the bathwater...
If he can do this at home, why hasn't a pharmaceutical company made something equivalent for the incredibly large population of lactose intolerant people around the world?
It wasn't done at home. It was done in a lab by someone who majored in biology for the express purpose of finding a cure for his lactose intolerance.
It's been a bit since I watched the two videos* he made, so I don't remember the details. But it was the first time I ever felt anything positive about gene therapy. I'm too used to seeing people like me treated like Frankenstein's monster so people can do cool science and not care about the suffering of their human guinea pigs.
But most likely the short version is that he was only using this on himself. He didn't need to get FDA approval or do clinical trials.
That's an enormously frustrating process for the folks with incurable conditions who just tear their hair out over decisions to deny approval because something bad might happen down the road. We tend to feel like "Let me live long enough to have those problems, you ass!!!!"
But those processes exist for a reason. (Look up Thalidomide if you care to know how wrong things can go.)
Maybe someday there will be a readily available gene therapy for lactose intolerance. Maybe his work will be the starting point for it.
* He has made a lot more than two videos but there are two specifically about this gene therapy he administered to himself.
As hard as for anyone who couldn't afford a $1000 drug or someone who couldn't afford a $100...
The ugliness of inequality fueled by capitalism is more pronounced in medical treatments, I've witnessed it firsthand several times.
In early 90s as 6-7 year old I had to undergo a revolutionary treatment at most expensive private hospital in India, days before surgery the doctor privately demand a large sum of unaccounted money. This repeated several times for subsequent surgeries and my father had to go in large debt each time.
We were a middle-class family by Indian standards yet my family's lifestyle were severely limited by from my medical expenditures, A poor family doesn't even stand a chance. What's worse is that the doctor had made incorrect diagnosis of my ailment at that time which lead me to a life-threatening recently.
This is what worries me about the COVID pandemic, Medical professionals who honestly believed that they're doing a service to humanity rushed to the front lines without any regard to their or their family's safety and many of them have perished. Now the ratio of corrupt entrepreneurs masquerading as medical professionals who flew to COVID-free islands during pandemic to the medical professionals who treat their profession as a service has now further worsened.
I'm confused, they say it was priced at $1 million because that was what they felt the drug was worth compared to the ongoing therapies needed to keep these patients alive. Ok fine. But once it became clear no one was going to pay that price, wasn't there some lower price that would still earn them a profit?
Probably not, the article mentions that the genetic mutation effects about two or three people out of a million, so that’s ~20,000 doses required to cure everyone in the world. The vast, vast majority of those people are going to be people without insurance or government provided healthcare that would ever pay enough to make a difference, so they’ve got to recoup their entire R&D expenses selling the 2,000-3,000 doses required to treat the combined population of the first world, and then maybe provide it for ~free to the rest of the world where there’s no chance of making any money anyway, as is generally the case with all expensive drugs.
If they cave and sell it at a price that doesn’t recover their R&D costs (mentioned in the article to be hundreds of millions of dollars), then that’s that, they’ve just lost all of that money. If they sit on it there’s at least a chance that someone in future might pay them for it.
>If they cave and sell it at a price that doesn’t recover their R&D costs (mentioned in the article to be hundreds of millions of dollars), then that’s that, they’ve just lost all of that money. If they sit on it there’s at least a chance that someone in future might pay them for it.
sure a chance in that it is not impossible the same way that a talking centaur with the ability to blow up planets with its mind is impossible, but given what we know about economic reality it is practically impossible that the million dollars per patient will be paid.
There's a saying that one should not throw good money after bad, in this case it would seem they are refusing good money because it won't cover the bad.
Also tax writeoffs exist, so I'm not sure what that R&D actually cost them?
> There's a saying that one should not throw good money after bad, in this case it would seem they are refusing good money because it won't cover the bad.
They are a drug development company, marketing their drugs to national government health services and private insurance companies. This is an iterative game, in game theory terms. Caving and selling at a loss just guarantees that counterparties will refuse to buy at the stated price next time too, and wait for them to cave and sell at a loss. Sitting on the drug until the parents expire and losing the entire investment rather than selling at a loss has the benefit of proving seriousness in future price negotiations.
And the article mentions that the ongoing care costs for someone with this disorder is hundreds of thousands of dollars per year. In the years since they refused the $1M price tag in an attempt to drive a hard bargain, the national governments and private insurance companies have no doubt spent more than $1M per patient they refused to buy a dose for.
Hardly seems like planet-destroying centaur levels of implausibility that they may eventually come around to the idea that $1M was actually a perfectly reasonable price, given the circumstances.
> Also tax writeoffs exist, so I'm not sure what that R&D actually cost them?
I think you have some major misunderstandings about what tax writeoffs are and how they work.
>In the years since they refused the $1M price tag in an attempt to drive a hard bargain, the national governments and private insurance companies have no doubt spent more than $1M per patient they refused to buy a dose for.
I wouldn't make the assumption on that, given the disease is potentially deadly. I would more likely make the assumption that the private insurance companies especially did the math and figured they end up a couple hundred thousand ahead in the most likely scenarios. But I'm prone to cynicism.
>> Also tax writeoffs exist, so I'm not sure what that R&D actually cost them?
>I think you have some major misunderstandings about what tax writeoffs are and how they work.
perhaps, but I do experience that sometimes in my business it can make sense to spend money on things and make less profits in order to have less taxes to pay, on paper things might look worse off but I somehow feel that I'm doing better nonetheless.
obviously comparing my business as a consultant to a pharmaceutical company is like comparing a single raisin to a field of watermelons, but I am of the opinion based on reading that the benefits of spending money to reduce profits and taxes seems to be greater the larger the business, and thus that the principle must hold.
Business losses offset profit, rather than taxes owed, and though losses can be carried forward for years to offset taxes, a company does at some point need to turn a profit for the tax benefits of its losses to matter at all. The article mentions that the company took investor money for this, and it seems to be a fairly small pharma R&D company, so I doubt they have some pile of other successful drugs that they are offsetting these losses against.
But moreover, losing money for tax purposes only makes sense in a narrow window dictated by tax rate. Leaving aside tricky confounders like government R&D grants, if your corporate tax rate is say, 10%, and you have an investment opportunity that won’t turn a cash profit but will grow the value of your business by 95% of what you invest, it can make sense to make an unprofitable investment and lose 5% on it over realizing the profits, paying taxes, and losing 10% on it. But for this to make sense you have to have an investment opportunity that already very close to breakeven, corporate tax rates aren’t that high. And just throwing money away to count the losses on your taxes never makes sense.
>The article mentions that the company took investor money for this, and it seems to be a fairly small pharma R&D company, so I doubt they have some pile of other successful drugs that they are offsetting these losses against.
ok but it would seem to me that supposition sort of works against the supposition that they don't want to lower the price because then they would not be taken seriously in future negotiations, unless the company has some other sources of revenue to keep them going it would seem unlikely they would be available in that future.
in fact in the article it says
>In the 2 1/2 years it took to win EMA approval, AMT, which had no other products to sell and no revenue from Glybera, lost millions of dollars. The company was formally liquidated in 2012. Its assets were acquired by a new private company, uniQure.
from the quotes in the article there are 100s of millions invested in uniQure but I'm not sure if that investment was made because people were like 'whoa, they got this million dollar drug!', if so seems weird that investors would invest for that reason because if I heard a company was selling a million dollar drug my next question would be 'how many billionaires need that drug?'
next question would be why governments themselves don't develop those drugs. I'm for the free market however bad it's in this case, unfortunately/fortunately it's the best instrument we got
>And let's not forget that this business often operates with sickeningly huge profit margins.
This is grossly misinformed
Looking at the UniQure Tax filings for 2020, They had 37M in revenue, -122M in R&D expenses, and -42M in general expenses, so they were -125M in the hole that year.
Who are you referring to in your 80% example? Also, what do you mean by purged? Do you mean stopping manufacturing of an approved product?
No company is gonna cut a an approved drug with hundreds of million in net profit because the % profit is <80. I could see them cutting drugs if the total profit is low tho. This helps them focus on other more profitable drugs with. That is to say, most companies don't want to be making 100 products that net low millions each. They want a few products that make 100 million+ each.
Sounds like I see it as more believable than you, but with the caveats that I added in my parent company. I doubt <80% was the only reason and any of the products were massive revenue makers.
It's a matter of principle. Perverse principle but principle: "Why would we? [lower the price] Pricing shouldn't be a political decision. It should be a rational decision based on merits and values," he said. "Hundreds of millions of investor money has gone into the company, and if there is no return for those investments, there will be no new drugs because nobody's going to do that in the future, right?""
Which is to say that you have an investor group that expects to either be paid or they'll take their medicine away and the public be damned.
Or perhaps a perverse process. The system is how you get new, actually amazing drugs. The system is also how actual health care has become really terrible in the US in particular.
Buying the rights on drugs like this, and more important expensive drugs, an license them under a freedom-protecting license (similar to GPL) could be a major application of charity funds.
You would still have to raise several hundred millions of dollars of funding to reconduct development and clinical trials for the drug after securing the IP.
Clinical trial data and manufacturing know how cant be leveraged from the original approval.
It is incredibly difficult to get investors to fund a second round of development for a product that made it to market and still failed.
You might say this is an opportunity for the government to step in as investor, but they have little interest, knowing that they could use the same money to save many more lives in other areas.
There's also the very small market for the drug. There's a lot of administrative and logistics cost in making a drug available on the market. If they could sell 1,000 doses a year they would have found a price that worked.
"...The first drug ever approved that can fix a faulty gene.
It's called Glybera, and it can treat a painful and potentially deadly genetic disorder with a single dose — a genuine made-in-Canada medical breakthrough..."
Never mind non-practicing entities for software patents, but surely for patents on medicine keeping them valid when no one is making any is entirely bogus and not deserving of legal protection?
If you invalidate people’s patents for trying to sell their drug at a price high enough to recover R&D costs, they’ll just stop doing R&D for any drugs that will have niche target populations.
This isn't the same though, this is invalidating patents for drugs that have been developed that no one is producing anymore.
Patent protection makes sense to inventivize development and production. In this case development already happened and only production stopped. So it doesn't make sense to uphold this patent.
If losing your patents in a position like this is a possible outcome, it changes the investment calculus. As it stands, there’s still the possibility that administrations or laws will change and governments or insurance companies will come around to wanting to buy it at a price that recovers the investment, or some other company will believe that they can persuade buyers to buy at a worthwhile price and buy the patents or the production rights off of the current owners. Or maybe some other company will profitably deploy a derivative technology and they can sue to recover some of their investment. For all of these reasons the patents and trade secrets are still worth something. If finding yourself in this position means that you are stripped of your patents and receive nothing, that makes drug R&D an even riskier investment proposition. Being stripped of patents by the government after having bankrolled clinical trials because the government refused to pay the price required to recover the investment would be a brazen show of bad faith and a real stab in the back. The patents will expire in a decade or so anyway, do we really need the government to go out of its way to screw these people out of their last possibility of making back some of the money they spent on this socially valuable work? If we think that it’s so important that this treatment be made immediately available to people at a low price, maybe the government should buy the patents early for the several hundred million dollars that they cost to produce?
I don't want to sound like a communist but it's not people who are holding patents and funding research. Usually research is funded by governments by subsidizing universities and research institutions or by companies.
So we can have governments continuing to subsidize research, but forbid universities and research institutions to sell the rights to only one company.
In the example we’re talking about here in the article, university research generated the treatment itself, and then a pharmaceutical company spent hundred of millions of dollars conducting clinical trials and bringing the drug to market, including wrangling with regulators and lobbying EU politicians directly to get acceptance of the safety and efficacy of the treatment in spite of the small sample size of the trials due to the extreme rarity of people with this disorder.
So the question of who did the initial research and who funded it isn’t really important to the question of whether invalidating patents left and right will negatively impact the rate at which new drugs are brought to market.
If the government wants the company’s patents and distribution rights, at this point I’m sure they’d be willing to sell everything over to the government at cost. Clearly no government is interested in buying the rights for $200M, any more than they are interested in buying doses for $1M each. The company that brought this treatment to market has clearly gotten utterly screwed here, and the nature of the comments on the article suggest that a lot of people here are disappointed that no governments have intervened to screw them even more for the audacity of thinking that they should be compensated for their work.
Perhaps the lesson here is that maybe seizing their parents for not selling their treatment at a loss isn’t actually a bad idea. Maybe there’s no risk of discouraging pharmaceutical companies from developing expensive treatments for niche conditions, since it’s already clearly a terrible idea, and companies already won’t be making the mistake of ever doing it again.
India has been doing this for decades. Somehow the global pharmaceutical industry didn't collapse despite of Indian drugs being exported for very cheap.
It's just a lie, one of very many we tell ourselves.
The lie people tell themselves is that because India does it, everyone could do it without disrupting the rate at which new drugs are researched and brought to market.
As I’ve discussed in other comments, this is why pharma companies have to recover their entire investment off of sales in the first world. The rest of the world is never going to buy their drugs at a price that would make the R&D spending worthwhile. This is why companies sell their drugs for much cheaper in countries where incomes are much lower, and also why drugs produced and sold cheaply in other countries generally can’t be legally imported into the United States. It’s also why claims that drug prices could be lowered in the United States by importing them from countries where they are sold more cheaply are fundamentally ridiculous. The reason drug prices are high in the United States and to a lesser extent in Europe is that they are subsidizing the rest of the world by doing substantially the entirety of pharmaceutical R&D spending in the world.
"Peter Bach, a researcher at Memorial Sloan Kettering, and his colleagues compared prices of the top 20 best-selling drugs in the United States to the prices in Europe and Canada. They found that the cumulative revenue from the price difference on just these 20 drugs more than covers all the drug research and development costs conducted by the 15 drug companies that make those drugs—and then some"
"To put the excess revenue in perspective, lowering the magnitude of the US premium to a level where it matches global R&D expenditures across the 15 companies we assessed would have saved US patients, businesses, and taxpayers approximately $40 billion in 2015, a year for which the Centers for Medicare and Medicaid Services (CMS) reported that total US spending on pharmaceuticals was $325 billion."
It seems to me that it’s not just the price of a single treatment that is too high, but also that the patients are fully recovered and don’t have to pay a recurring annual subscription fee to live normal lives. Or is that too cynical?
My, you innocent child, that you have to ask this.
(I have a genetic disorder commonly treated with one of those drugs that cost $300k annually.)
Edit: I was going to delete this in short order but now that it's flagged, I'm leaving it. People with genetic disorders get all kinds of hatred from the world and medical system for just wanting to be healthy and how dare we say that online.
Discussing the value of a human life, and figuring out how much the many are willing to sacrifice in order to treat the needy few, isn't something that should be out of bounds.
I don't think the voices of the few should be silenced.
Its uncomfortable maybe, but I think not a discussion to avoid.
Our economic system requires endless amounts of busy work. If that busywork doesn't exist people will compete for a handful of jobs because they cannot comprehend the idea of doing less work per person.
If that busy work consists of keeping people alive and advance medical science it's at least a better use of human potential than working via door dash.
It is in fact too cynical. The company that wanted to sell this drug isn’t the same as the companies selling recurring treatment to people with this disorder. Your cynicism has blinded you to the fact that the marketers of this drug do not have any economic motivation to do what you are suggesting. Their economic motivation is to sell the tiny number of doses required to treat everyone in the first world (2,000-3,000) at a price high enough to recover their investment and make a profit.
No, because other gene therapies like Zolgensma are priced at $2.5M for a single dose and selling quite well. There is a huge market for these types of cures.
Article explicitly mentions price is high because there are no recurring costs, so it actually isn't more expensive than other treatments that may cost hundreds of thousands every year.
Iirc economists have estimated that a human life is valued around 3M$ by society (a couple of years ago, probably higher now), the price doesn't necessarily seem too high.
No that is not what they implied just that so far it has only been 10 years. These people are still healthy but the company can't say it lasts 30 years because no one has lived long enough to see if it does. It may last indefinitely.
Society itself is collectively responsible for this failure, not the patent owners. Funding could have been provided through charity, or through legislation. But this was not done, and instead development of this drug was left up to profit seeking investors.
It isn't the investors' duty to bankrupt themselves to produce this drug. They tried to find a way to get this produced through the private sector, and they found that it was impossible. It should instead be handled through the public sector, and it is the general public who are ultimately responsible.
The flip side of patent expiration is that a rival company would need the infrastructure and capability of manufacturing the drug.
For something like Aspirin, that's not a high bar to clear, an avid experimenter could probably do that in their basement, but for gene therapy drugs I feel confident in saying that it's orders of magnitude higher.
Then again, they could kickstarter it and say that if they get X orders or raise Y money they'll do it, make and sell the 20-30k doses for everyone and then close up shop with a healthy profit.
"...
Her blood becomes thick and white with fat particles that can destroy her pancreas.
All her life, Turcotte has had to follow a strict diet. She can't eat cheese or chocolate or any food that contains fat. And she can't drink even a drop of alcohol."
Fascinating story and the use of virus to repair genetic anomalies. What other uses can there be of similar conditions? And why aren't we hearing more of it (if the approach is viable)?
I wish I knew why these patients can't have alcohol. I mean the biological mechanism. What the relationship is between misprocessing fat and alcohol being deadly.
Alcohol changes the structure of the liver cells and slows down the liver’s ability to process fats. This is the second way that triglycerides begin to accumulate and the levels rise. This is also the beginning of fatty liver disease.
I am equally curious. Fatty liver can be a consequence to high alcohol consumption, but people can also have NAFLD. My guess (IANADr) is that alcohol leads to excessive build up of fat in their bodies.
NAFLD is also highly correlated with diabetes, so I wonder if there could be something to learn from studying this or related genes.
Price should be based on cost of production, not on how often the drug is needed. So stupid not to make it available because someone was crazy to price it that high.
A drug with high cost of production that’s not needed very often will cost a lot of money per dose. The article mentions that hundreds of millions of dollars were spent on R&D and clinical trials, and maybe a couple thousand people in the first world have this disorder. Development costs have to be recouped entirely off of first world sales, since the rest of the world isn’t going to ever pay any appreciable amount of money for a drug, so even if they could sell this to everyone in their target market the breakeven cost seems like it would be about $100,000. Since they’re not going to be able to sell to everyone (there are limits on what various governments and private insurance will pay for medical treatment), and since ongoing care for this disorder costs hundreds of thousands of dollars a year, $1M/dose seems like a perfectly reasonable price.
How much does it cost now, after all the R&D and tests are completed? I doubt they need millions to actually produce the drug once they know how to and that it works. So they basically prefer not to produce it at all, than to sell it at affordable prices. It makes no sense to me.
I think it makes no sense because you are greatly underestimating the cost to produce and market the drug, even after sunk costs. It could easily be many hundreds of thousands of per dose.
It looks like uniQures business model is to take risky products through clinical development then sell them to other manufacturers. Faced with no buyers and large costs to keep it on the market, they chose to pull it.
We can speculate on what the cost per dose would be with no profit, but ultimately, there wasn't enough profit at a reduced price for uniQure to provide it.
The fact that no other companies are licensing the drug shows that they agree that there isn't enough of profit to be made.
Well, that's my point. They developed it, but no one can make it now even if it's cheap to actually make (not to pay licensing for it). Probably patents and such. Not a big fan of such kind of methodology for medicine where profits trump benefits for people.
But you have to consider that nobody works for free and patents expire.
If nobody thought they could make money, Glybera would never have made as far as it did.
You could start a non profit to make Glybera today as the main patents are expired, but nobody would give you the money to develop it and run trials without a profit motive.
Charities and the government have better ways to spend money than help a few people with a rare disease.
If you want to get rid of the profit motive, you have to find something better to replace it.
It just barely got approved by the EMA and based on feedback the company didn't bother to pursue FDA approval.