Where's the Generic Insulin?
psmag.com
psmag.com
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.
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.
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.
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.
You can replace drugs in the above phrase with pretty much anything.
Prices are what the market can bear (until of course someone else comes with a cheapest solution and ruins the competition)
But then again, MS, Apple, and several other products are priced per country as well.
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.
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."
Tesla vs Model T?
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.
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...
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 :)
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.
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...
I'd love to see such a product become available, but I've learned not to hold my breath.
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.
[/rant]
I'm a type 1 and I use them, and they read pretty accurately with the CGM that I do shell out for.
The trouble is not paying for it, there is help, the trouble is they make it a huge pain, with annoying paperwork.
(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.
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".
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.
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?
They're the ones trying to make something created by the Heritage Foundation seem "Socialist".
Why won't the GOP take responsibility for what its behaviors are doing?
I'm really curious.
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.
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.
Trying not to mention how things are funded is a bit like Basil Fawlty trying not to mention the war.
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.
Thanks for the tips though, I'll at least stash the names of those programs away just in case.
It practically cost you nothing to call and see.
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.
Also, many companies have compassionate care programs to get access to people who simply can't pay for expensive biologics.
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.
For completeness of links: here's the NEJM article page:
(On the first vial of $25 Walmart Novolin N for a diabetic pet)
Insulin's amino acid sequence varies a little by species, but as far as I recall most mammal's insulins are interchangeable.
http://www.npr.org/blogs/health/2015/03/19/393856788/why-is-...
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.
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%?
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.
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.
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.
Oh wait, that would be the European / communist solution. Can't have that.