Time for a history lesson. From 1922 until 1981, the only insulins available commercially were extracted from bovine and porcine pancreases -- a process which was both expensive and dangerous, since if the product was insufficiently purified it could cause life-threatening immune reactions or carry diseases from the animals used. (This is why insulin-using diabetics are to this day not allowed to donate blood in most of the world.)
It took sixty years between discovering insulin and figuring out how to produce it biosynthetically (all modern insulin is now produced by genetically engineered yeast or E. coli). This yielded so-called "regular" insulin, which -- at the concentrations necessary to make it feasible for injection -- has the unfortunate property of hexamerizing. As a result, it has is peak activity about 3 hours after injection, and ends its activity around 6 hours after injection -- compared with endogenous insulin, which acts within 5-10 minutes, but is excreted 24 hours/day.
In 1996, we finally had "rapid" insulin -- Insulin Lispro, which adjusts a couple amino acids in order to prevent hexamerization. This makes it act roughly twice as fast as regular insulin, roughly matching the time taken for a meal to be digested and to enter the bloodstream -- thus reducing the postprandial "peak" and cutting down on the chronic hyperglycaemia related complications of diabetes.
Remember how I said that regular insulin stops working after around 6 hours? If you want to get 8 hours of sleep, that's not so good. In the 1940s and 50s some modified insulins were released which "slow down" the insulin so that it lasts for longer; but it wasn't until 2003 that the first "24 hour" insulin was released.
So why is insulin still so expensive, 90 years after it was first introduced? Because the insulin we're using now is a heck of a lot better than the insulin 90 years ago. You might as well ask why a Tesla is so expensive when the Model T was launched over a century ago.
Interesting—had no idea the 24 hour insulins were so new.
I think that also explains a certain trend I've seen with insulin usage guidelines (typically) given by doctors, versus by learned users. I found at first independently, then later had the finding corroborated, that using meal-time insulin (e.g. Humalog) was too unpredictable: too many factors are involved; blood sugar almost always go too high or too low—and, unpredictability varies with dose size (even while 'appropriately' matched by carbs). So, many people, including myself decide that since the lowest dose is most predictable, use zero (this is a Type 1 speaking)—zero meal-time insulin that is—and compensate by eating an extremely small number of carbs. This is only possible because I have the 24 hour insulin running in the background, however. My perplexity about it was that doctors seem unaware of this strategy (in my experience, which, while limited does extend to several doctors, and I hear this consistently from other diabetics). Instead, there's this myth that you just calculate your carbs, match with insulin—everything's good! But if it's only been around for 11 years or so, I guess it takes a while for the literature to catch up.
The other side of the situation, at the risk of sounding unappreciative, is that it feels like I'm paying Tesla prices, but still opt to get out and walk most of the time since the car is so bad.
Better blood sugar monitoring tech (e.g. continuous) and quicker meal-time insulins would seriously improve things. Quicker is better since carbs convert to blood sugar more rapidly than the insulin acts—unless I take a large insulin dose. That's another aspect of insulin's unpredictability: its processing rate is proportional to dose size, so there isn't just one ratio of insulin-to-carbs—though one could still infer their dose->(insulin units/gram of carbs) function :)
So, many people, including myself decide that since the lowest dose is most predictable, use zero (this is a Type 1 speaking)—zero meal-time insulin that is—and compensate by eating an extremely small number of carbs.
Yes, a lot of T1s find that keto diets work well for them. (It doesn't work for me, unfortunately; if I drop below about 80g/day of carb my liver decides that I'm starving it and dumps crazy amounts of glucose into my bloodstream.)
Better blood sugar monitoring tech (e.g. continuous) and quicker meal-time insulins would seriously improve things.
We have continuous blood glucose monitoring. It's expensive and not very accurate right now, but it does exist. Faster insulins are one of the big targets for use in insulin pumps, because they would make a closed-loop system much easier (less need to predict where blood glucose is going if you can just wait 10 minutes, measure a new value, and give a new bolus), but there are two difficulties: 1. Diffusion from subcutaneous tissue into the bloodstream depends mostly on the molar mass, and insulin monomers are quantized; diffusing half of a monomer would be faster, but it wouldn't be useful. 2. People need to be able to "unplug" pumps from time to time without dying, and if ultra-ultrarapid insulins leave the body too fast the mere act of taking a long shower could become life-threatening.
Interestingly, I know someone who's the chief scientist for a company that has developed a non-invasive blood glucose meter. It measures the glucose content from earlobe.
http://www.groveinstruments.com/
Looking at that page, the funny part is that someone decided to use the marketing term "cutting edge" for a technology that specifically does not cut your ear to measure blood glucose...
Considering the name "Optical Bridge technology", I'm guessing this is yet another company trying to use the slightly different absorption curves for water vs. water-with-dissolved-glucose? This is not a new idea; I've seen lots of companies try this and fail because they (a) weren't accurate enough, (b) needed frequent recalibration, (c) were thrown off by exercise, dehydration, or common medicines, or (d) all of the above.
I'd love to see such a product become available, but I've learned not to hold my breath.
> From 1922 until 1981, the only insulins available commercially were extracted from bovine and porcine pancreases -- a process which was both expensive and dangerous
From the medical paper being summarized in OP:
"A series of innovations in the insulin manufacturing process in the early 1970s helped to improve purity and reduce these side effects. In short succession,
Novo introduced “monocomponent” insulins and
Lilly introduced “single-peak” insulins. These
safety improvements extended insulin patents
into the late 1980s...Although recombinant insulin was heavily advertised as a clinically superior
agent in the 1980s (Fig. 1), almost no evidence
was provided to demonstrate its superiority to
the best available animal-extract insulins. 26"
> This makes it act roughly twice as fast as regular insulin, roughly matching the time taken for a meal to be digested and to enter the bloodstream -- thus reducing the postprandial "peak" and cutting down on the chronic hyperglycaemia related complications of diabetes...but it wasn't until 2003 that the first "24 hour" insulin was released.
From the medical paper:
"Although long-acting analogues cause less hypoglycemia than NPH does, 27 it has yet to be shown that analogues lead to better long-term outcomes than standard recombinant human insulin does. 28"
> Because the insulin we're using now is a heck of a lot better than the insulin 90 years ago.
"On the whole, insulin today is
demonstrably safer and more convenient to use
than products available in 1923. But whether
each incremental innovation is worth the price
we pay, in a world where insulin remains unaffordable to many patients with diabetes, is less
certain."
"Although long-acting analogues cause less hypoglycemia than NPH does, 27 it has yet to be shown that analogues lead to better long-term outcomes than standard recombinant human insulin does. 28"
Doctors vs. patients. Regardless of what doctors may think, as a patient I can assure you that not randomly passing out due to hypoglycaemia is a better outcome. Similarly taking one shot of basal insulin per day is better than three shots per day.
"On the whole, insulin today is demonstrably safer and more convenient to use than products available in 1923. But whether each incremental innovation is worth the price we pay, in a world where insulin remains unaffordable to many patients with diabetes, is less certain."
Bovine and porcine insulins didn't go away simply because newer insulins were more profitable. They went away because 99.9% of patients didn't want them any more.
> Regardless of what doctors may think, as a patient I can assure you that not randomly passing out due to hypoglycaemia is a better outcome.
I think you are exaggerating. Cite please. You also aren't addressing the other points: you claimed animal insulin was extremely dangerous and this justifies the continued monopoly through recombinant patents, when the paper specifically says that almost all of that safety problem had been dealt with.
> Bovine and porcine insulins didn't go away simply because newer insulins were more profitable.
That's pretty much what the paper argues, actually...
The costs of bringing new drugs to market are not simply artificial. Quite aside from the costs of developing the drugs in the first place (tweaking a couple amino acids is cheap; knowing which amino acids to tweak is a bit harder) and the costs of production (significant in the case of insulin, considering the lengthy process for biosynthesis and then purification), demonstrating that a new drug is both effective and safe costs billions of dollars.
Novel insulins are harder than most drugs too, since insulin is very closely related to some oncogenic hormones. A lot of novel insulins have died in trials when animals were found to have increased rates of cancer.
Sorry, I meant: pharma drug prices, not development costs. Prices are artifically created, rather than being purely based on supply and demand.
I know plenty about pharma costs, having worked for one and studied the area of biophysics including protein engineering extensively. My point is that the prices of drugs are only weakly correlated with the costs of bringing a drug to market.
More importantly (and kind of ignored by most) is that pharma R&D costs are shared between many drugs. For example, Genentech has a huge R&D division and there are people who work on general projects that benefit all their biologics.
Also, there are ridiculous inefficiencies built into the process of bringing drugs to market, many of which are designed to avoid large-scale adverse outcomes, or to make it possible to track where the adverse outcome root cause is.
We're talking market forces here. Yes, the drug companies will try to squeeze as many dollars out of the market as they can; the counterbalancing force is that if they get too greedy, someone else will enter the market and undercut them.
The fact that entering the market is so bloody expensive is why drug companies can set their prices so high without provoking a new competitor into existence.
Perceived value added and range pricing is one of those invasive diseases that have managed to take root across such a wide range of human culture that it will take decades to find a cure, especially since it is doubtful that industry is working particularly hard on the problem.
Pharma is a bit different from typical pricing, though. Note that pricing is done per-country, based on mean ability to pay- so there will always be some number of people below a percentile who can't (that's why pharma has compassionate care programs).
>So why is insulin still so expensive, 90 years after it was first introduced? Because the insulin we're using now is a heck of a lot better than the insulin 90 years ago. You might as well ask why a Tesla is so expensive when the Model T was launched over a century ago.
That analogy would make more sense if I needed a car to continue living. It feels somewhat akin to being okay with amputees having to live with peg-leg style prosthesis in the first-world due to being under-insured.
Some people think that healthcare should be subsidized by societal infrastructures (whatever government you're a part of) due to the inherent benefits that a healthy society provides for itself and its' citizens, not including whatever morality certain folks subscribe to.
In short : People tend to feel as if it is particularly low-brow for pharmaceutical companies to engage in the same type of strategies that you see normal capitalism-centric companies engage in, even if they are driven by that same normal capitalism, economies, and market.
Insulin would still be expensive if medicine were subsidized, you just wouldn't see the price tag yourself. I don't disagree with your point, but it doesn't seem entirely relevant.
Heh, was just wondering this at the pharmacy a couple of days ago... For one type of insulin I use (Lantus), it costs $400 for ~2.5 months worth, without insurance—which I happen to be without atm. Frustrating.
What's worse are the prices for 'test strips' for blood sugar monitors, though: about $120/mo for the cheapest kind, and insurance doesn't help much.
And what you really want is a continuous monitor, but they're over twice that last I checked.
And what you REALLY want is a glucose monitor/insulin dispenser feedback loop—or a new pancreas (speaking for Type 1's) :D —but those solutions obviously have their problems as well.
If you're in need of cheap test strips- get the Wal-Mart brand meter and strips. The strips are something like $9 for 50, instead of the $1 per strip I'm used to paying even when I was on insurance.
I'm a type 1 and I use them, and they read pretty accurately with the CGM that I do shell out for.
I'm also a type 1 and highly recommend the Walmart Reli-On test strips. Cost savings on those is amazing. I do have the Reli-On meter and they work great together.
Wow, that sounds like a great deal. I'd been using True Test and True Track, from Kroger dealers and Walgreens. There isn't a Walmart anywhere near me (downtown Boston), but I'll see if I can get 'em online.
The store-brand meters and strips are usually a great deal if you don't have insurance, but the catch-22 is that most Rx insurance won't pay for the generic strips, just the name-brand ones.
From this side of the Atlantic, or really probably from any country that has some form of assured health care, the notion that you could have to go without insulin in the states is... baffling. Utterly baffling.
Best of luck with it!
Health care US style is enough of a barrier to contracting and start-ups that it seems a pretty reasonable topic for a site focused on exactly those groups of people.
It's embarrassing. For years a lot of Americans just hoped they didn't get sick. Obamacare has helped, but people are falling through the cracks. Insurance companies took advantage of the bill, and raised rates to the point where
some/many unemployed people can't afford private insurance, or qualify for medi-cal.
(To all the Obama naysayers--he tried.
By the time Republicans got through scaring people, he needed
to include private insurance companies, just to get something
passed. And something is still better than what we had before--Nothing!
No insurance--own house--get sick--go to hospital--get jacked up bill--can't afford to pay--hospital lawyers eventually receive judgement on lawsuit--eventually attach home--quietly evict you! This scenario is still possible.
I hear about these earnest individuals(without assets) and refusing to declare bankruptcy still struggling to pay off
their medical bills. Go ahead, but just know the rates they
charge you were padded, and you are paying the highest rates
they can charge you? Even if you pay cash, and they half the
bill(antidotal stories I have heard on the fact machine) you
are still paying way more than anyone with collective bargaining agreements(Insurance companies). Don't be a hero?
It's a rigged system.
Yes--I have a bit of anger towards the medical system.
Insurance companies took advantage of the bill, and raised rates to the point where some/many unemployed people can't afford private insurance, or qualify for medi-cal.
I think you are very mistaken. The ACA added additional regulations that limit insurance company profitability (80% rule). The reason rates went up is because the legislation demands insurers provide more (coverage of children up to 26, caps on out of pocket, no pre-existing condition limitation). I'm not saying they were bad ideas, but anyone in their right mind knew that would increase costs not lower them.
"To all the Obama naysayers--he tried. By the time Republicans got through scaring people, he needed to include private insurance companies, just to get something passed. And something is still better than what we had before--Nothing!"
That's an...interesting...spin.
The Democrats had the votes to pass any bill they wanted.
They passed that one.
Sorry, you don't get to blame it on "Republicans".
"The Democrats had the votes to pass any bill they wanted."
Do you honestly believe Ben Nelson, Blanche Lincoln, Joe Lieberman and Evan Bayh (among many others) would vote for any bill Obama wanted? That's not factually true, so I'm wondering why you believe it.
Are these people Democrats who would not vote as instructed by the party leader or something? Pardon my ignorance, I'm from the UK where MPs who do not vote as instructed by the whips (enforcers) have the whip withdrawn (are expelled from the party).
I also noticed the attempt to change what I actually said -- "any bill they wanted" to "any bill Obama wanted", which I didn't say.
They had a majority in both Houses and could thus have passed any bill they, collectively, wanted (in fact they did it without a single Republican vote, and without allowing any amendments or even very much debate).
They passed that bill. Obama then signed that bill. That, my friend, is factually correct.
Why this desperate attempt to make it somehow the fault of "Republicans"? How about taking some responsibility?
Yes. They have already proven they will. The Democrat party had a much tighter reign on its people in 2008 through 2010. The simple matter was, you vote along the party line or we will not support your reelection nor will you serve on any committee of consequence.
The Republican party is a bit more fractured, which is how all political parties should be. People should be scared of a political party where dissent is heavily punished and nearly absent. The reason is because it expressly puts the party before the people.
Fortunately the voters have three times shown the error of that thinking and the resulting control of Congress is the result. As for the office of the Presidency, politics of identity (race/sex/etc) has become the norm and unless the Republicans participate in that type electioneering they won't get into the White House.
Are you without insurance because of income or a "qualifying event" like losing a job? If so, you should look at Commonwealth Connector (re: income) or the ACA options (if you had insurance that went away). Even a very cheap plan may end up including prescription coverage that includes those test strips (disclaimer: the only person using test strips whose finances I know anything about is on Medicare, which covers almost all of the cost).
I quit my job, having some limited savings, in order to finish a project I'm working on (+ other reasons). So I probably won't qualify. I may look into it a little more, but my estimate at this point is that putting the time into figuring it out will likely cost more than just paying for it. I'll have insurance again within half a year.
Thanks for the tips though, I'll at least stash the names of those programs away just in case.
Quitting your job is a qualifying event. You definitely qualify. I was looking at Obamacare because I want to start a startup. I considered signing up by February and just have two insurances for a while rather than go without health insurance (since I graduate from my PhD program mid year, and would then lose my health insurance in August). But I researched this just in case, and turns out that's wildly unnecessary, and the system is set up for things like this.
Voila, if you had insurance through a job, school, whatever, and lose it at any time due to a job change (whether quitting, or firing, or whatever), that's a qualifying event that allows you to sign up for new insurance within XYZ days of the event.
I'm pretty sure leaving a job, even on your own accord, is a qualifying event that you can use to get subsidized healthcare. You should definitely look into what option are available.
Your resumé says you live in a state that expanded medicaid. Eligibility is now entirely income-based, NOT asset-based. If your current income is below the cutoff, you qualify for medicaid, period, end of story.
For a while there was an insulin-smuggling system organised on Compuserve to get bovine insulin into the US.
Some people with diabetes said that human insulin didn't give them the same hypo warning signs; bovine insulin wasn't available in the US and import was banned under BSE beef bans.
How much Lantus do you use? In Poland I was paying around $100 for 5 pens, in UK not much more (without insurance). Test strips (Accu-Chek) arround $15 for 50.
I use 20 units daily. I believe the units are 1/5 mL each. That's definitely a better price than I can get here—although I did just find out I can do the old jar/syringe thing for $267! Ugh.
The prices quoted here seem rather low for a biologic drug. The way insulin is made is somewhat complicated, the best standard is typically production in yeast, followed by reverse proteolysis, then purification and formulation. The chem. Eng. Flowchart is ten 'steps', most requiring lots of chillers; insulin is not at all a thermostable drug (patients know this, over time insulin will flocculate and become useless)
Sure, but as has been pointed out, pricing doesn't just include the cost of manufacture- drug pricing includes the ability of the country to pay for the drug. Pharma amortizes costs globally.
Also, many companies have compassionate care programs to get access to people who simply can't pay for expensive biologics.
Cost is however a lower bound. Insulin at $200/month pales in comparison to generic herceptin at $20k for a six month? course. Of course herceptin is made in mammalian cells; going to a microbial platform might result in a 10x decreasr but that's still about 300 a month on razor thin margin.
Perhaps we need a regulatory change to allow import of a drug when it would be legal to make a generic in the US but no manufacturer is willing to do so.
Even better, perhaps this could be combined with aid to the country the drug is imported from. I was just reading an article on insulin outside the US that talked about an 8 year old girl that died because her family could not afford the cost of insulin (about $1.50 for 40 units).
We could allow Americans to import insulin from India if the American buys twice as much as they need, with 1/2 of their purchase being given to a poor Indian who needs but cannot afford it.
Thank you. All the other links mentioned (including the OP) are news pieces about this NEJM article, which is itself a cracking good read, very accessible.
For completeness of links: here's the NEJM article page:
The article fails to mention that you can get a vial of insulin (regular or NPH) without a prescription at Walmart for $25. Not generic, but inexpensive. The rapid acting and the once daily insulins are indeed very expensive, but $25 will get you the very best the early nineties had to offer, just like most drugs that were expensive name-brand drugs back then.
It's the standard size of a vial of insulin - 1000 units, same as the extremely expensive insulins referenced in the article and by other people in this thread. How long it lasts depends on how much you need to use, which can vary widely.
Just for clarification: Does Walmart sell an Insulin approved for human use? Animal insulin has been used for human use, and human insulin for use in pets...
Insulin's amino acid sequence varies a little by species, but as far as I recall most mammal's insulins are interchangeable.
Novolin N is human insulin. Walmart pharmacies likely sell more than one brand/type, this was just the one my vet prescribed (although a formal prescription isn't necessary, you just have to ask the pharmacist for it). It was about $25, so I assumed it was the same stuff the parent comment was talking about.
You can get by if you're desperate, but the 28 days isn't an underestimate. The dropoff is pretty fast after the four week mark. I don't understand why, but that's been my personal experience.
Perhaps the right policy to serve the public interest is for Uncle Sam to pay the patent owner $1B for each of the remaining years on its insulin patent and then 'genericize' today's insulins.
The shareholders would earn their profits while the public would be served by gaining immediate access to superior diabetes treatment for a trivial cost of perhaps $20B -- a pittance when compared to the current scenario where millions of diabetics worldwide continue to suffer because unthinking pols continue to publicly kowtow shamelessly before the altar of Capitalism.
How about getting universal healthcare with a single payer system (at least state wise) so instead of having a billion smaller organizations with a more limited buying power that can't get you the best prices?
You know why in the UK drugs cost 20-25% on average of the US price, not because of subsidies but because the NHS provides healthcare for 60M people and they say we are paying X for the drug now bid.
Your local HMO not to mention an IPA simply can't do that.
But anyhow as people have stated Insulin even the "older" versions is insanely expensive to fabricate and purify, it's simply not something that a generic company will go after. Most generic companies go for medicine which is easy to produce and is compatible with their existing fabrication capabilities.
You know why in the UK drugs cost 20-25% on average of the US price, not because of subsidies but because the NHS provides healthcare for 60M people and they say we are paying X for the drug now bid.
That's not why drugs are cheaper in the UK. The largest US health insurance company is United and it covers almost 40M people. More than in all of Canada. Yet United pays more for drugs than Canada.
Also, drugs in the UK don't cost 20-25% of the US price. Maybe you meant 75-80%?
regulatory compliance for biologics (stuff made by living things) is a bitch compared to normal chemicals... maybe the generics companies don't find it worthwhile.
on the other hand, making insulin with transgenic bacteria is practically kitchen chemistry, if you're not scared of injecting yourself with your own product.
You can't make insulin from bacteria that easily. It's a two chain protein, and stitching together the two chains kinetically competes with precipitation of one of the chains. One chain insulins are typically ineffective (well someone did once engineer a working single chain insulin - Michael Weiss at Cass Western) because signalling requires insulin to unfold, which down not happen when the chains are attached to each other.
If you try to design an insulin analog yourself be careful. Insulin cross reacts with the igf-i pathway; igf, like most growth factors, is oncogenic, so you'll have to be vigilant about getting cancer down the line.
I'd like to add that it might not be impossible to spin up production of a generic low cost insulin... Or to develop direct to generic IP free insulins, but the newer insulins are preferred because of very nice pharmacodynamic properties. That said, the bestiary of insulins we have now is quite comprehensive and as they fall off the patent cliff I think the future looks nice for generics
oops, thought it was a simple short peptide... refolding from inclusion bodies is still kitchen chemistry, although it probably wants some expensive chromatographic cleanup regardless of how it's made. since pancreas is essentially a waste product, maybe it's easier to do that and the switch to recombinant insulin was for consistency/better analogs.
I would guess it has more to do with demand. Once recombinant insulin came out, most folks switched, a few didn't. Unfortunately, "a few patients" aren't enough to support an entire product line.
First off, insulin is HARD TO MAKE. Its synthesized rDNA, this isn't the same as making pills out of powder from china and selling it at a 40% discount with plenty of margin still. This has to be grown and made in a lab with a very high precision.
Second off a bottle of insulin is like 25 bucks..... Boo freaking hoo. Most people cant wrap their head around how insane that is. You are buying f*ing DNA.. that someone made.. that's saving your life.. for 25 bucks.
It took sixty years between discovering insulin and figuring out how to produce it biosynthetically (all modern insulin is now produced by genetically engineered yeast or E. coli). This yielded so-called "regular" insulin, which -- at the concentrations necessary to make it feasible for injection -- has the unfortunate property of hexamerizing. As a result, it has is peak activity about 3 hours after injection, and ends its activity around 6 hours after injection -- compared with endogenous insulin, which acts within 5-10 minutes, but is excreted 24 hours/day.
In 1996, we finally had "rapid" insulin -- Insulin Lispro, which adjusts a couple amino acids in order to prevent hexamerization. This makes it act roughly twice as fast as regular insulin, roughly matching the time taken for a meal to be digested and to enter the bloodstream -- thus reducing the postprandial "peak" and cutting down on the chronic hyperglycaemia related complications of diabetes.
Remember how I said that regular insulin stops working after around 6 hours? If you want to get 8 hours of sleep, that's not so good. In the 1940s and 50s some modified insulins were released which "slow down" the insulin so that it lasts for longer; but it wasn't until 2003 that the first "24 hour" insulin was released.
So why is insulin still so expensive, 90 years after it was first introduced? Because the insulin we're using now is a heck of a lot better than the insulin 90 years ago. You might as well ask why a Tesla is so expensive when the Model T was launched over a century ago.