But they don't. Health systems in Europe apparently refuse to pay for this therapy. The reason for that, from reading other articles, appears to be that it is of questionable efficacy. Patients report fewer pancreatitis attacks, but clinical indicators like blood fat levels are apparently unchanged. The tiny market and efficacy concerns might explain why the therapy is no longer available at any price.

It is amazing to me that we can manufacture and program viral particles to target specific cells. In my case, my treatment is a non-nucleonic technique that didn't repair the actual chromosomal hereditary defect but inserted a working gene, additional and freely available genetic material into my liver cells. It's amazing that the body can just recognize this extra bit of code and just start producing the factor. The engineer in me is also impressed they can make so many copies of the engineered virus.

It appears to be working. My factor levels have steadily increased and I’m now no longer a severe or even moderate hemophiliac. I’m their first patient to have achieved these results for hemophilia A severe and it puts me well into the therapeutic range. It really feels like I have been given a new body, it’s indescribable. For the first time in my life, I’m pain free.

It’s a weird feeling. Pain, mostly from bleeds into my joints, has been my constant companion. I was never able to do sports as a kid and had to avoid many other activities that would put me at risk. I have mixed feelings about all of this. On one hand I’m extraordinarily grateful, and the other side I see what a huge disadvantage I’ve been at compared to others for all of my life. I thought this day would never come, I had resigned myself to my limitations but now they are gone in a matter of weeks through the miracle of a medical experiment.

My old medication, a replacement clotting factor that was synthetically produced in a lab, worked but not nearly as well as this. Not to mention the fact it cost over $100,000 per month and I had to give myself an IV every other day. It's truly been a life changing experience for me, and I hope that gene therapy becomes widely available to others.

Also, the thing that was a milestone in this case was that the Hemophilia A factor VIII gene has been notoriously difficult to create a genetic therapy for because of the complexity of the actual gene itself. On the scale of what the body produces, its one of the more complicated proteins. So it basically means many other genetic conditions will be able to be treated with and addressed with similar technology.

Such an exciting time to be alive, and yes there are amazing things happening right now despite all the bad news you may hear!

The patent will expire within a few years, setting the stage for generic manufacturers to step in, but the article doesn't mention it.

In the US, patent protection extends for 20 years after the earliest filing date for the application on which the grant is based. There can be adjustments to the term if the grant was delayed.

https://en.wikipedia.org/wiki/Term_of_patent

The article is fuzzy about the timeline of events, bu has this quote:

The stunning results of the mouse experiments were featured on the cover of the journal Human Gene Therapy in September 2004. The cover image showed how, week by week, the mouse blood changed from milky white to a clear, transparent red, illustrating just how effectively the gene therapy was working.

So it seems like a good first guess to put the patent filing at or before 2004.

If so, then the Glybera patent would expire sometime after 2024. At that point, generic manufacturers can step in to sell their version of the product, assuming regulatory approval.

Van Deventer says the company never considered lowering the price. "Why would we? Pricing shouldn't be a political decision. It should be a rational decision based on merits and value."

If no one will pay $1 million, your revenue is $0. Assuming the drug costs much less than $1 million to make, surely any revenue number is better than $0?

At that threshold, to pay for an £800k drug treatment you'd need to give someone 32 extra years of life (or 64 years at double the quality of life and so on). This is enough to pay that kind of amount for life saving gene therapies, especially if given to young children but not enough to treat something that can be largely managed through diet control.

Since the majority of the world's patients are in Quebec, I don't understand why the provincial government doesn't cut a deal for this drug. I'm sure they'd rather sell it $250k a dose to a nice big patient population than at $1m to nobody. Quebec has a lot of pricing power here as the only large potential buyer.

But it's not working here. The patent holder is effectively saying society isn't allowed to have the invention. They're using a legal means meant to share the knowledge with the world to instead horde it away from the rest of us.

When the system doesn't work, the system must be improved. How can we incentivize inventors to not do this?

The Drugs for Neglected Diseases Initiative, a nonprofit which grew out of Doctors Without Borders, just received approval for a pill that successfully treats African Sleeping Sickness.

>Ultimately, the drive for approval cost $63 million and involved clinical trials including 750 patients in Congo and the Central African Republic. Two million villagers were screened.

The costs were paid by seven European countries, the Bill and Melinda Gates Foundation, Doctors Without Borders and other donors.

https://www.nytimes.com/2018/11/16/health/sleeping-sickness-...

edit: the downvotes probably assume I mean the patient is going to pay out of pocket. of course not. the insurance companies would be paying. the only inferiority between gene therapies and non-cures is their pricing structure. we invented a solution to this problem thousands of years ago: debt.

As terrible as it sounds, this logic seems sound to me. If we think having this type of drug is worth the > $100MM it took to develop, then health systems should either fund the $100MM research, or they should let private companies do it and pay them fairly for their work. $1MM for something so expensive to develop with so few possible users doesn't seem crazy to me.

If the $100MM is in fact not worth it, then, well, you get the situation we have now.

I'm sure a lot of people will read this article and think the owners/funders of the drugs are the bad guys. But nobody can be expected to work for free.

Likewise with drug manufacturing, it's the same idea. It's illegal to copy a pharmaceutical drug and take it yourself and others without the approval of the patent holder. Yet, it is the patent holding party that determines how many licensed copies it is willing to sell. Thus, they are able to take the moral high ground in pricing this drug, but it's the same principle as above-pony up for my idea, shame on you for benefitting from it and not contributing to my wealth.

I really do think this company is out of touch with reality. All in all, I feel like this only earns them bad press, especially after Martin Shrekli debacle. There's also a potential for a lawsuit, based on human rights I'm sure.

I'm pretty confident LPLD sufferers around the world would be prepared to move to the LPLD hot spot in Quebec, and work part time in the factory under proper supervision?

There's an old Chris Rock bit about Big Pharma where he says there'll never be another cure for HIV like there was for polio because there's no money in that. The money is in getting you to the next stop.

It's poignant because this isn't a theoretical scenario. Gilead recently was downgraded on declining revenues because they're wiping out the disease (Hepatitis C IIRC?).

So, back to Glybera. There are plenty of low-incidence diseases that are treated by expensive drugs to manage them. This is a lifelong commitment. Covering such drugs in company health plans can significantly increase the per-member costs.

If you have a drug that essentially cures the drug in one dose shouldn't that be weighed against the lifelong cost of covering a regime to manage the disease that is inferior? Multiply that by the disease being quite rare and sure, you end up with a $1 million price tag.

As further evidence for how screwed up the US health insurance system is: companies enroll in plans for their members typically for a period of a year or maybe a few years. Let's say your drug's price of $1m compares favourably to $100k/year for 40 years to manage the disease. How can a company who might only be covering the employees for 1-3 years be expected to cover that higher cost?

To be clear, this is further evidence of how stupid the US model is. In a single payer model this particular concern goes away.

How many rare genetic disorders are out there where $1 million per patient for an essentially complete cure isn't a bargain compared to the cost of managing the disease? Probably a lot. Is it fair to decry such expensive drugs just on their price tag without looking at the facts? Probably not but I bet you it will happen.

So what would you charge for a drug that guaranteed you would live 30 extra years after you spent 20 million to develop it?

For an added twist, let's say it's NOT FDA approved but you have solid clinical evidence that it's efficacy was solid and can your "street cred" (whatever that means in biotech) allows you access to the world's most successful (ie richest) people.

I have my answer...what's yours?

Why not?

If there are so very few patients, a lab could easily produce enough for them.

Say, if gene therapy became common, there wouldn't be as much red tape for approving this particular one, and there might be machines or research that could be shared with other drugs to amortize the cost?

The money quote. A rational decision? Maybe. Exactly what merits? Exactly which values?

"Hundreds of millions of investor money has gone into the company"

But none of that led to the development of the drug.

I thought that drug patents were basically illegal in India. It seems there’s a huge market there for this kind of thing. An abandoned drug with a huge price tag.

Also I’m not terribly worried. The patent will wear off eventually and then anyone can make it.

And it's especially weird that he thinks pricing shouldn't be political when his product has a government-granted monopoly and the bulk of its customers will be government-run health-care systems and government-licensed insurers.

Sure, there's a real question of how to pay for treatments for rare diseases. But the millions in development are a sunk cost. To take his ball and bat and stomp off would be disappointing in any circumstances. But when people will die because of it?

It's basically the same reason most businesses throw product away rather than just distributing it for free.

The gist of the problem is this:

> The Amsterdam company spent more than $100 million testing the drug and carving a path through Europe’s medical rules and regulations, which weren’t geared to consider a new technology like gene therapy. Initially, for instance, regulators said they expected a clinical trial of 342 patients. Executives wryly noted that there were only 250 people with the disease in all of Europe.

> Nor has Glybera convinced the national regulators in Europe who decide what drugs get reimbursed. Last year, French authorities said they would not pay for the drug. Germany judged Glybera’s benefits “non-quantifiable.” It leaves doctors and insurers to make decisions on a case-by-case basis.

Here's a drug that cost $100 million to make, and will require even more money to move through clinical trials in the U.S. And the pool of potential patients is a less than 1,000 people, and oh many of then can't pay either because they lack insurance (U.S.) or the cost/benefit panel math doesn't work out (Europe).

Viewing this after-the-fact leads one astray, into thinking there is some problem with the system that leaves this potential cure out of the hands of patients. Patents, money, it's all just a proxy for effort in, benefit out. Even if you had the government make this drug, you're talking huge amounts of money per patient, which few governments would pony up. (And rightfully so, because you could save a lot more lives with that amount of tax dollars.) The answer is probably that this drug doesn't make economic sense, and the abandonment of it by the maker is just an indication that it was a misguided effort to begin with.

The problem with alipogene tiparvovec probably isn't the IPR†. Rather, it's that the treatment is extraordinarily expensive to administer (ironically, because it's something close to a total cure with a long-term impact, the drug seller is required to provide long-term monitoring to patients), has a microscopic market (that's why it's so expensive), and is of questionable effectiveness --- it improves quality-of-life metrics but not necessarily clinical ones like blood fat levels. Many (all?) national health systems in Europe, where it is approved, refuse to pay for it.

If the drug had a clear market, even if the current owner no longer wanted to provide it, it could license to some other drug company. But it's likely that no other viable concern wants to shoulder the costs and uncertainty of this particular drug. That's not the fault of the patent system.

† In fact, it's possible that the patent here has expired; I'm still trying to confirm that, but it would explain why the treatment had "orphan drug" status in Europe.

Patent is a system to freeze the invention from society for 20 years.

But in this case, patent alone is not on the blame. Still we need to change the patent system something like the patent holder must offer patented product or license the patent for reasonable price or face losing the patent.

"If it's not commercially viable to produce a certain therapy, unfortunately, in our Western society, it does not happen."

And it is far from clear that this is not as it should be, because it's not just LPLD carriers about whom tear-terking stories can be told. $1M can be deployed in other ways that could potentially save more lives. Instead of "Sorry LPLD carriers, you have to die now", it might be, "Sorry, 100 poor African children without access to clean water, you have to continue to die of dysentery so we can save this one LPLD carrier."

Yes, it's essentially a Prisoner's Dilemma. If every insurance company agreed to pay for this drug, the total cost of treatment overall would be lower (and the patients would be healthier and happier). If my company decides to pay it and no other insurance company does, then when the patient leaves our network (in less than 10 years) and joins another insurance network, my company will have paid the cost but can't reap the financial benefits.

There's two major differences between this scenario and classic PD, though.

First, companies are allowed to communicate. We could conceivably get everybody in a room together and come up with some agreement by which everybody agrees to pay for this drug, even if patients switch insurers. Everybody wins. Patients are healthier, and insurers save money.

Second, it's not a one-time decision. An insurer can change their mind from "no" to "yes" at any time. So it's more like "iterated PD", with an indefinite number of rounds. In that game, interestingly, there is no strictly dominant strategy, and altruism tends to do better in practice! So maybe you don't even need an agreement.

> To be clear, this is further evidence of how stupid the US model is. In a single payer model this particular concern goes away.

How do you figure? The article points out that they also had trouble convincing European governments to pay for it. You can't get Glybera anywhere in Europe or Canada today, either.

The US model is arguably a poor one, but this isn't a good example of that, because every other country in the world failed at Glybera, too.

The following choices assume that more people living an extra 30 years is a good thing ethically, and that there are no devastating effects environmentally or otherwise. The following choices also assume that you'll always have a monopoly on the production of the drug.

1. Assuming that the supply is practically unlimited, an altruistic actor should probably give it away for as close to free as possible. A purely selfish actor should probably try to sell to each individual for as much as they can afford (though this can be hard pricing strategy to enact). I suppose you might actually want to charge less than that even as a purely selfish actor, since you wouldn't want to somehow destroy the world economy by making everyone really poor except for yourself (would this actually destroy the economy though? I'm not sure... probably not relevant for the purposes of this thought experiment).

2. Assuming supply is limited, a purely altruistic actor will have to choose the most fitting recipients. This is a really tough choice. How do you define the most fitting recipients? Those who are most likely to contribute to the betterment of humanity with their extra 30 years? It seems like an almost impossible task to pick out who these people would be. A purely selfish actor should charge the richest as much as they're willing to pay.

If it were me and supply were unlimited, I'd like to think that I'd sell it for as little as possible but enough to still never have to worry about money again. Making $10 million in profit would probably be more than enough (though if you can make more and still help everyone, that'd be even better). If supply were limited, I don't know what I would do.

One thing I just realized though, is that even if supply were unlimited, if you had this godly power, you might choose to withhold it those you deem unworthy, which is a whole other ethical can of worms. I'm guessing this kind of deviates from the intent of your thought experiment though.

What's your answer?