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Comment by rayiner | Hacker News Reader

> I don't understand. My understanding of why insulin is so expensive: intellectual property laws are enforced by the government preventing businesses without that intellectual property to compete in the space.

That’s not an accurate understanding of intellectual property specifically. Insulin isn’t like a pill, where once you have a chemical formula you can make millions of them very cheaply. It’s a biologic, an artificial hormone. Even leaving aside the patents, it’s very expensive to get approval for a generic biologic (called a biosimilar). That’s why there are few manufacturers of synthetic human insulin, even though that’s out of patent.

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Hi Rayiner, you are spot on with your analysis. My name is Eric, and my non-profit, Project Insulin, is tackling this problem head-on as well. We are developing a biosimilar insulin and will distribute it directly to patients at cost. The drug development process is still expensive but much cheaper because of the Biologics Act that was passed in 2020. When going through the FDA approval process, biosimilar insulin makers don't have to do phase 2 trials, and their phase 1 & phase 3 are focused on interchangeability with the reference product rather than proving that insulin is a way to lower high blood sugars.

Another obstacle, as you pointed out, is that there are few manufacturers who produce synthetic insulins. From what I've learned in my discussions with manufacturers is that many are transitioning their facilities to a focus on mRNA drug manufacturing. Therefore there is a limited set of manufacturers who don't make insulin but have the equipment/facilities for it (in the U.S.).

Hi Eric! I'm a T1D and so super interested in this space. Can you comment on whether it is the case that "modern" insulins (Lantus and Humalog/Novolog, in my case) are both covered by current patents, and also considerably better for patient outcomes (faster acting, more predictable -> lower A1c) than non-covered insulins? That is my understanding for why cheap, high quality insulins are not available, but I'd love to be informed if it is not the case! Thank you for your work in this area!

(not OP). some quick googling reveals lantus is no longer covered by patents. patents in the usa last 20y, and they filed the main patent for that drug in 1994.

it looks like they tried to patent some pen injection mechanism as a way to artificially extend the patent, but the patents were tossed out. I think that's a similar approach to how the Epi-pen people have maintained control, except their pursuit was successful (epinephrine isn't exactly a new chemical, nor is the process for manufacture).

still--manufacture of these drugs is long and expensive process, esp with fda approval. new entrants want to recoup their cost. the public is a great institution to develop generics because it can happily do so without a profit motive.

I think Humalog/Novalog patents expired a while back. These companies will probably focus on other newer drugs for profitability like Semaglutide which is useful for dealing T2D and obesity.

Another thing that needs to be investigated is how much the PBMs (Pharmacy Benefits Managers) prpfit from the spread of drug pricing. Are they marking these drugs up a lot? Do they need to be tightly regulated?

Jokes on them. I can buy raw semaglutide powder two steps off a Google search at 10% of retail.

Hi as some of the others have already mentioned Lantus is off patent. My organization is focused on insulin glargine but there are generic versions of insulin lispro and aspart. Which is the generic/biosimilar version of humalog/novolog. We decided to stick with glargine first and transition to the other versions as we progress.

Hi Eric, my name is Francesco. In the last three years we industrialized a novel method for producing biosimilar insulin (in Italy). We are an international team and I really would like to contact you. Can you write to the email you find on my profile?

Hi Francesco looks like you found me! I will respond to your email shortly :)

Hey Eric, somewhat tangential question -- why is it that seemingly all precursor manufacturing is done in China or India? Is it just a low-cost game or are regulations making it too expensive to do in the U.S. or something else?

This is a great question. Simply it is a lot cheaper to make drugs in China + India. The APIs cost less, and the workforce is cheaper. With regards to regulations I don't want to generalize but it has been well documented that it is hard for the FDA to regulate drugs being produced outside of the United States.

Why is insulin not expensive in other countries?

While I don't know the answer to this in-depth I can share some bullet points and of course it depends on what country you are talking about. On top of that it is important to note that there are insulin shortages in various countries.

- one payer healthcare systems - non-convoluted distribution systems - depending where cheaper workforce/cheaper to make the insulin - less stringent regulatory processes - stronger lobbying groups in the US

There are no shortages in Australia, only the Eli Lily brand is low in stock but all other brands are available.

I've never heard of anyone unable to find insulin in Australia.

https://apps.tga.gov.au/Prod/msi/Search/Tradename//53488

Very cool. This is much needed.

People dont want insulin (traditional insulin.) They want fancy insulin (modern insulin), because it is convenient. They want modern rapid and long acting insulin. They want pens. Maybe people want the inhalable powder. Those innovations exist outside the original insulin patent. They are also mixing other drugs with the insulin.

>Average retail prices of Novolin and Humulin (traditional short- and intermediate-acting insulins) have gone down, or held steady, while prices of modern rapid- and long-acting insulins continue to go up. On average, traditional insulins now cost less than half of what modern insulins cost.

https://www.goodrx.com/healthcare-access/research/how-much-d...

There is a lot more going on that makes high end insulin expensive. A lot of conversation around insulin is people talking past each other because they are referring to different things that they think should be free, usually one of these additional features on top of the hormone itself.

I do agree with the statement that some of the language around the lack of insulin availability is misleading, but it's not just that it's more convenient. "Fancy" insulin allows one to better manage blood glucose levels. Poorly managed blood glucose strains various organs/systems in the body and over years and decades leads to various health complications, some resulting in death. (It's still a lot of work and stress -- modern insulin isn't an automatic improvement; but it does allow greater success in managing diabetes.)

(My comments here are in the context of type 1 diabetes. The (potential) positive health impact of modern insulin may be less pronounced for other diabetics.)

I dont mean to be dismissive or elitist. There is enough wrong with the medical system, that if somebody loses coverage and needs to see a doctor to get their prescription changed, that change alone becomes insurmountable, behavioral change not included.

My rub is that the conversation is dishonest. Saying "access to insulin is a right" and then changing the topic to modern delivery methods and such. Call a spade a spade, and have the direct honest conversation the first time. My pertubement goes beyond this topic into social justice/political correctness and just about anything. I may believe in the cause and the result, but be dismissive of how to get there by cheating and hacking peoples attention spans. It seems the only way to be an activist and get attention is to start with a lie, and now everybody is competing for the most inflammatory headline.

Everything you said is the conversation everybody should be having, instead of truncating it to "insulin is way too expensive."

I think a big problem is that short acting insulin, which was available 25 years ago, used to cost $9usd / 10 mL bottle now costs ~$80 with insurance (in california) or $200+ list price for an effectively equivalent short acting insulin. (numbers were from my insurance statements which include the cost for current prices, and from a family member who was on the pharma board at one of the large managed health facilities in california in the 90s.

To me, that cost inflation is purely artificial and not driven by any new tech relating to the insulin itself.

For T1 diabetics, the cost increases have been moving to insulin pumps which have infusion set costs in addition to the actual pump, and for continuous glucose sensors.

Are you sure about this? 25 years ago, rapid insulin would have still been under patent.

Is anybody buying short acting anymore? At those prices? Rapid onset is $72.88.

https://www.walmart.com/cp/3769564

That's basically a 4.4x increase, after inflation to jump from short to rapid. Not saying its justified. Why pay $200 list for something that is less than $80.

Yeah, you can do some quite easy motte-and-bailey with it.

Everyone will agree that (cheap, out of patent) insulin should be available to all; it's literally lifesaving.

But then switching that to the (modern, convenient) insulin should be available to all is a bit of a slight of hand, especially when it is NOT a "you will die without this" but a "you will have more hassle taking medication to not die" scenario.

I do want to bring up that insulin management is extremely taxing to individuals, and hard to get right. See https://news.ycombinator.com/item?id=30376777 for previous discussion.

Obviously the costs involved in implementing these technologies should be part of the discussion, but I don't think it's unreasonable to want to make anything that eases management of diabetes way more affordable.

Which is what the conversation should be, and how it should be framed.

The press writing "life saving insulin" headlines takes away from the ability to discuss that: within the last decade or two, modern improvements made the process of managing diabetes significantly easier and else stressful. The drug companies gave everybody a taste of an easier life, and then jacked up the price, saying "pay us more or go back to the old way." At what level should the government step in and subsidize or control this quality of life improvement? At what level should its creators be rewarded?

I am old enough to remember when the entire world took traditional insulin. It wasn't pretty.

I would like to point out that these fancy insulins have been around since 1996. I do agree that there is cheaper insulin available, but as others mentioned there is a significant change in quality. But I agree with you that the conversation should be affordable high quality insulin.

Another piece of the insulin ad drug saga that I haven't seen many people discuss here is the distribution of drugs. The distribution from manufacturers to patients is incredibly inefficent with a variety of middle organizations increasing the cost associated with distributing the insulin and those costs are pushed down onto patients. Our website has a simplified graph showing the current model vs what we plan on doing: https://projectinsulin.org/why-insulin/

For a more in-depth look the Wall Street Journal has a great video from 2019: https://www.wsj.com/video/series/news-explainers/how-drug-pr...

I assume when you say 1996, you mean Humalog/insulin lispro? That falls in the rapid category, but I feel like most of the conversation about people wanting cheap modern insulin is the long acting right? The primary quality of life improvement people seek is having to inject only once a day, plus extra if diet requires?

I was dating 20 years from glargine (invented 1994, approved 2000), which is technically still patent protected somehow, despite biosimilars being approved. It takes a while too for Doctors to switch over when new paradigms are delivered. The real metric should be when long acting overtook intermediate acting prescriptions.

For anyone looking for history of modern insulin. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045187/

yes apologies glargine was approved in 2000. And I agree it does take a while for doctors to switch. Something interesting that I have recently learned is that it may even be hard to find clinical trial participants because doctors will be hesitant to take patients who have good reactions to their current insulin off of that insulin to be a part of a clinical trial.

I will also say that Pharmacy Benefit Managers (PBMs) also have a lot of power when it comes to influencing doctors to begin prescribing new drugs.

> At what level should the government step in and subsidize or control this quality of life improvement? At what level should its creators be rewarded?

You assume that creators are rewarded.

In Sweden you get the insulin and pens for free (that is, you've paid for it with your taxes).

And it was invented there? When I say create I mean discovered not manufactured. The R&D.

And the answer/solution is somewhere in the realm of a public/private hybrid, where the government is funding short term expensive, long tail benefit research.

> And it was invented there?

This is beside the point. You pay for insulin, but with taxes. In return, you don't have to deal with "do I eat or do I get insulin".

> When I say create I mean discovered not manufactured. The R&D.

The question remains: are the creators actually rewarded?

In the US most R&D now is performed by small companies, government entities, or with government money. Large companies buy this research cheap and profit from it immensely. There are cases when all new drugs that appear on the market are based on public government-funded research.

The amount of revenue that goes back into R&D decreased while revenues increased.

More data here: https://www.cbo.gov/publication/57126

Novolin 70/30 ReliOn vial (10 mL; 100 iU/mL) has had a flat price since 2014. The Novolin 70/30 ReliOn FlexPen (3 mL; 100 iU/mL) pen has been the same price as the vial since mid 2018 when it came out.

The price of these drugs NEVER went up.

Framing it as only "more hassle" or "purely convenience" really downplays the difference in the quality of life improvement the last decade has brought everyone.

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