Why insulin so expensive?

Why does insulin cost so much to patients in the USA and around the world? Why is insulin, a widely sold drug of which most forms are now off-patent, so incredibly expensive? These are simple questions, but ones with a number of complicated answers. This post will break some of those answers down and point you in the direction further reading if you want to dive deeper.

1. Only 3 Companies Control 90% of the Global Insulin Market

The ‘big three’ insulin producers – Eli Lilly, Novo Nordisk and Sanofi – dominate more than 90% of the world insulin market by value. Often only one of these companies supplies insulin in a country, which means they more or less hold a monopoly there and can set prices as they wish. In some countries, notably China and India, there are domestic insulin companies that can help drive down the price. This means we need more companies in markets like the USA to help bring prices down. We’ll touch on that a bit further down the list.

2. No Generic Insulin

When it comes to the question of generic insulin, we are faced with another complicated issue. Insulin is a therapeutic biological product (or ‘biologic’), rather than a chemically synthesized molecule. This means it cannot be made as generic in the same way as other drugs. Creating what is called a biosimilar is a lot more complicated and expensive than just duplicating a chemical molecule. There is little market incentive to produce biosimiliars because it costs nearly as much as making new drug, and companies must go through all the approval stages and trials that a new drug is required to go through. Not to mention, current biosimilar insulins on the market – primarily produced by the ‘big three’ – have only reduced the price by about 10-15%. For more on biosimilars and the 2018 FDA announcement read this and this.

3. Pay-for-Delay Schemes & Lawsuits

A ‘Pay for delay’ agreement is a patent dispute settlement in which a generic (in the case of insulin, a biosimilar) manufacturer acknowledges the original patent of a pharmaceutical company and agrees to refrain from marketing its product for a specific period of time. In return, the company receives a payment from the patent-holder. This means it is actually legal for one insulin producer to pay another one not to enter the market. A few years ago the company Merck announced plans to sell a biosimilar version of Sanofi’s Lantus. Sanofi sued, and eventually Merck announced that it was no longer pursuing it’s biosimilar, presumably due to payments from Sanofi to stay away. If Pay for delay schemes don’t work, the ‘big three’ can still sue other players, prolonging processes and pushing players out of the market because of legal fees and time-wasting. All of these are win-wins for companies, and lose-lose for patients.

4. Patents

Why aren’t we seeing more companies making insulin? There are many reasons for this, but patent evergreening is a big one. Patents give a person or organization a monopoly on a particular invention for a specific period of time. In the USA, it is generally 20 years. Humalog, Lantus and other previous generation insulins are now off patent, as are even older animal based insulins. So what’s going on? Pharmaceutical companies take advantage of loopholes in the U.S. patent system to build thickets of patents around their drugs which will make them last much longer (evergreening). This prevents competition and can keep prices high for decades. Our friends at I-MAK recently showed that Sanofi, the maker of Lantus, is no exception. Sanofi has filed 74 patent applications on Lantus alone, that means Sanofi has created the potential for a competition-free monopoly for 37 years.

5. Politics

Companies are not in the habit of throwing money away, and they are not in the habit of staying out of politics. Eli Lilly, Novo Nordisk, and Sanofi collectively rake in several billions of dollars in profits. That’s not millions, but billions – with a B. We know they spend millions on marketing, but they also spend millions on lobbying politicians and donating to our decision-makers so that they keep quiet about price gouging. Check if your representatives receive contributions from one of the ‘big three’ insulin manufacturers or any pharmaceutical company. Chances are, they do. Not to mention, the revolving door between pharma companies and US Government positions. Our current secretary of Health and Human Services was previously an Eli Lilly executive. Obviously, his interests are not with people, but with power. This is why independent patient voices are so important.

6. Price Fixing

These Business Insider graphs pretty much say it all.

Several lawsuits alleging some form price-fixing are currently in the works. You can read more here and here.

7. Pharma Marketing Schemes

Physicians in the United States and some other countries are allowed to collect fees from pharmaceutical companies for talks, advice, and more. Supposedly, these are to compensate physicians for their expertise and time. However, they can create loyalty to a company and may influence prescribing habits – a belief shared by some pharmaceutical salespeople. In some countries like India, physicians are allowed to sell and profit off insulin directly through patients, or through pharmacies they themselves own, cutting out middlemen and the retail pharmacies. Thus, they lose the incentive to find the lowest price insulin for their patients. Insulin companies also focus on ‘insulin-starts’, or the insulin the physician diagnosing patients begins with. As patients are reluctant to change, a number of marketing and financial incentives are employed to influence this decision.

8. Payment for Influence (or Silence)

Many major key opinion leaders, influencers, and patient advocacy organizations take pharma cash. For example, the two biggest diabetes organizations – The American Diabetes Association and The Juvenile Diabetes Research Foundation – have accepted huge sums from insulin manufacturers. Other groups were actually created by money from the ‘big three’, like the World Diabetes Foundation which is funded by Novo Nordisk, and other supposed advocacy groups that are actually doing pharma’s bidding, or at least are highly influenced by them. If this issue is important to you, check the funders of an organization you want to support, and if it’s not transparent, you can ask if they take industry money.

What Can be Done?

Patients are speaking out about these issues all around the world. In the USA where prices have skyrocketed especially, T1International Chapters are being formed where patient advocates are educating and pushing for policy change. You can learn more about Chapter here and find more information and action related to the insulin price crisis here. Whatever you do, wherever you are – don’t stay silent.

Why aren’t we seeing more companies making insulin? There are many reasons for this, but patent evergreening is a big one. Patents give a person or organization a monopoly on a particular invention for a specific period of time. In the USA, it is generally 20 years. Humalog, Lantus and other previous generation insulins are now off patent, as are even older animal based insulins. So what’s going on? Pharmaceutical companies take advantage of loopholes in the U.S. patent system to build thickets of patents around their drugs which will make them last much longer (evergreening). This prevents competition and can keep prices high for decades. Our friends at I-MAK recently showed that Sanofi, the maker of Lantus, is no exception. Sanofi has filed 74 patent applications on Lantus alone, that means Sanofi has created the potential for a competition-free monopoly for 37 years.

More here, and yes there are a multiple of reasons, not just that one. Such as this:

… it is actually legal for one insulin producer to pay another one not to enter the market. A few years ago the company Merck announced plans to sell a biosimilar version of Sanofi’s Lantus. Sanofi sued, and eventually Merck announced that it was no longer pursuing it’s biosimilar, presumably due to payments from Sanofi to stay away.

Here is another relevant source. And this:

…Sanofi has filed lawsuits against both Merck and Mylan to prevent them from going to market with a generic lantus insulin (the Sanofi blockbuster drug).

Here is Vox coverage. Furthermore, fewer restrictions on foreign importation could solve much of the problem:

According to the Food and Drug Administration, “in most circumstances, it is illegal for individuals to import drugs into the United States for personal use.”

New bills by Peter Welch, Elijah Cummings, and Bernie Sanders would ease those restraints. It seems easy enough to address this problem without having systematic government purchases of pharmaceuticals. Insulin prices have risen as much as threefold over the last ten years, but that doesn’t have to be the case.

Colorado has become the first U.S. state to implement a price cap on insulin, with Governor Jared Polis signing the bill into law on May 22, 2019. “We will declare that the days of insulin price gouging are over in Colorado,” Polis said.

The Department of Law will also be investigating the pricing practices used by health insurance providers for their care plans, CBS Denver reported.

This law is a landmark victory for diabetics in the state and could signal a shift for diabetics across the U.S. being able to get affordable prescription drugs for their chronic illness. According to the American Diabetes Association, 1.5 million Americans are diagnosed with diabetes every year, and 9.4 percent of the population lives with the condition.

According to the latest version of the bill, which was signed by the President of the Senate, Leroy Garcia, on May 14, insulin prices rose by 45 percent between 2014 and 2017, resulting in one in four type 1 diabetics reporting underusing their insulin due to the high cost.

Nonprofit organization T1International reports that some users have to pay up to $1,000 a month due to their health care coverage plan. However, the cost of production for a vial of most analog insulins is between $3.69 and $6.16, according to T1International.

The annual medical cost related to diabetes in Colorado specifically is almost $4 billion, with $700 million used for prescription drugs. The total for the U.S. is $327 billion for diagnosing the condition.

According to the American Diabetes Association, the average medical expenditures among people with diagnosed diabetes were “2.3 times higher than those without.” Almost 20,000 residents of Colorado are diagnosed with diabetes every year, the majority of them being type 1 diabetics, each of them relying on insulin to stay alive.

The graphic below, provided by Statista, illustrates the U.S. states where adults have been diagnosed with diabetes as of 2017.

U.S. states where adults have been diagnosed with diabetes as of 2017. Statista

“This American Diabetes Association-supported legislation is monumental for people living with diabetes,” said LaShawn McIver, MD, senior vice president of government affairs & advocacy, American Diabetes Association.

“With the prices of insulin nearly tripling between 2002 and 2013, people with diabetes often face financial hardships affording their insulin. Many are faced with tough decisions to either cut back or skip doses or forgo other necessities to pay for insulin.

“Thank you to Governor Polis, Representative Roberts, and Senators Donovan and Priola for this legislation and their continued efforts to protect the more than 400,000 Coloradans living with diabetes,” said McIver.

The bill also states that the Department of Law shall be investigating the current price of insulin and whether it is low enough for users. A lobbying disclosure form in 2017 revealed that the Pharmaceutical Research and Manufacturers of America (PhRMA) spent $25.4 million lobbying the U.S. Congress, higher than the previous year.

A report is to be created and published on November 1, 2020, according to the bill, presented to Governor Polis. The report will include a summary of insulin pricing practices; public policy recommendations; and recommendations for improvement to the Colorado Consumer Protection Act.

This article was updated to include an infographic.

Colorado became the first state to cap the monthly cost of insulin at $100. Here’s why the life-saving drug is so expensive.

  • Colorado became the first state to pass a bill capping the monthly cost of insulin per resident at $100.
  • Type 1 diabetics need insulin to survive. Due to drastic price increases, many diabetics are struggling to afford the lifesaving drug.
  • In the past 15 years, insulin prices have tripled. There are only three manufacturers who make insulin and decide the price for insulin — their prices have risen at the same rates.
  • The insulin supply chain, like other pharmaceutical medications, is extremely complicated and opaque, so the consumer cannot see where prices get set and where they change throughout the supply chain.
  • Visit Business Insider’s homepage for more stories.

Following is a transcript of the video.

Narrator: Many people in the United States can’t afford insulin. The average price for one vial of insulin is about $285. Most diabetics need two to four vials per month. But here’s the thing. Insulin prices weren’t always this high. “Inexpensive, easily accessible.”

Narrator: A Type 1 diabetes diagnosis was a death sentence before this life-saving discovery.

Commercial: “The all-essential insulin.”

Narrator: Without insulin, an essential hormone that regulates blood sugar, your body can’t regulate how much glucose enters your cells, and your cells starve. The medical researchers who patented their invention in 1923 wanted insulin to be affordable for even the poorest sufferers from diabetes. Sure, there have been major improvements.

Commercial: “This new genetically-engineered insulin has two distinct advantages.”

Narrator: The most recent was about 15 years ago. Insulin’s still an old drug. It’s shocking that the price has increased so dramatically. When a drug has been on the market for enough time, its patent expires, ending its reign of market exclusivity and opening the door to generic competition. This should drive the prices down.

Jeremy Greene: And what’s happening with insulin is a real violation of our expectations, because this is an old drug that is now becoming inaccessibly expensive, long after its worth has been proven, and long after that cost of original innovation of these drugs has already been recouped.

Narrator: There are only three manufacturers making insulin for the United States drug market and the prices of their competing products have risen at the exact same rate. Even though the manufacturers have said that they set their prices independently, this shouldn’t happen in a competitive market. Even the newest variation of insulin has long been approved by the FDA. So you might think that some essential innovations happened in the past few years to warrant such a price increase, well think again.

Nicholas Argento: The products that are out are not really new. They may have tweaked the manufacturing process and the like and they have better delivery pens and the like, but the increase in price has been astronomical.

Narrator: So the product hasn’t really changed, just the packaging and delivery. And the high prices have pushed people to crowdsource money, using sites like GoFundMe.

Tan Mitchell: My son had started to not take his dosages as prescribed, because he knew we were struggling with trying to come up with the funds to get more insulin for him. We had not met the deductible.

Narrator: A diabetic with a high deductible insurance plan could pay for months of insulin prescriptions out of pocket until their their insurance kicks in.

Dylan Porteus: The part that was at the forefront of my mind was that I might die from this, I might not get what I need. The deductible was 5, 6 thousand dollars. Even with them covering half, six vials of insulin, they wanted $837.

Narrator: So how are these skyrocketing prices determined? The manufacturers make the drug and set the price. This is part of the reason why insulin is so expensive. There’s no limit to how high the price can be set, and they don’t have to disclose how they set it. The manufacturers negotiate with Pharmacy Benefit Managers to be placed on PBM formularies in exchange for rebates. These rebates and negotiations also don’t have to be disclosed. Formularies are a list of medicines that the PBM offers. The PBM negotiates on behalf of insurance companies, and the manufacturers give rebates to PBMs in exchange for lower placement on an insurance tier system. The lower placement usually leaves the patient with one option, as it’s the most affordable. It’s a good place for a brand to be, but it’s not always great for the patient. It leaves them with one option, and that option might not even be what their doctor prescribed.

Julia Lerner: It almost feels like insurance is working against us, in a way. I say, so I need X, and they only cover Y. Or I need a certain kind of insulin, and they just, they say that’s tough, sorry.

Greene: This is all wrapped in a web of secrecy.

Narrator: Business Insider reached out to the three insulin manufacturers. and they each cited the complexity of the supply chain as a reason for their high list prices.

William Cefalu: We think there are incentives at every level of the supply chain that facilitate or even encourage the high list price from the manufacturers, to the wholesalers, to the PBMs, to the health plans.

Narrator: And at this point, it’s safe to call what’s happening an insulin crisis. So why isn’t the FDA intervening?

Lydia Ramsey: The FDA can’t do anything around price. So the FDA can’t say, “You have to charge $150 for this, “and you can’t do anything different.” That’s just not how it works in the US. Other countries can have a little bit more sway.

Narrator: The US does not regulate prices. So that’s part of the answer. Insulin’s expensive because it can be. There’s no limit to how high the price can rise. The FDA regulates and approves drugs and grants patents. In the US, a patent excludes others from making an invention for a limited time, usually 20 years. Some critics think that manufacturers of insulin are abusing patents.

Susan Collins: For insulin, a careful look is warranted to determine if minor modifications were used to just extend the patent protections and discourage competitors.

Tahir Amin: What it becomes then is just the patent system has become strategy and defensive tool. How can I strategize to keep my competitors off? Forget about the patent system being about progressing the sciences and the arts, as the Constitution says. It’s become a business strategy.

Narrator: But patents aren’t the reason why a generic insulin doesn’t exist. Unlike chemical medications, like Advil and Zestril, there’s no generic insulin.

Ramsey: With a chemical drug, you have the same chemicals in it every single time. When it comes to a biologic-based drug, like insulin, that’s a much more lengthy process. You have to figure out how to make living cells look and feel exactly the same as the original version.

Narrator: The FDA approval process is lengthy and usually more expensive. In fact, out of all medicines in the US, there are currently only 17 FDA approved biosimilars. In 2016, a follow on biologic insulin, which is close to a biosimilar, was approved by the FDA. It was made by one of the three manufacturers, Eli Lilly, which didn’t exactly add a new competitor, and it didn’t really help the price decrease, which leads patients on their own to find another option.

Lerner: Here’s a group where people can go and say I don’t have the supplies I need, and I really need help.

Andrew Livingston: It’s very surreal to live in the United States and to buy life-sustaining medicine on the black market, you know?

Marina Tsaplina: You have a way to get it, somehow, somewhere. You have doctors who are giving their free samples away.

Livingston: The endocrinologist I saw would just give me whatever free samples she had lying around. Tsaplina: You go to Canada and buy your insulin.

Narrator: Recently, the public has been paying attention to the patient-led movement for affordable insulin.

Elizabeth Rowely: We really wanted to see people living with it who truly understand it being a voice for change.

Tsaplina: You don’t know if you will have enough of a freaking liquid that your whole life depends on. You don’t know if you have enough life. That’s what being not sure if you can afford your insulin means.

EDITOR’S NOTE: This video was originally published on February 27, 2019.

Why Is Insulin So Expensive In The U.S.?

A nurse in 1938 checks the amount of insulin in a needle. For many decades, the only insulin available to people with diabetes came from the pancreases of cattle or pigs. Insulin from animals is still available outside the U.S. — and cheaper than a recombinant DNA version. Bettmann/Corbis hide caption

toggle caption Bettmann/Corbis

A nurse in 1938 checks the amount of insulin in a needle. For many decades, the only insulin available to people with diabetes came from the pancreases of cattle or pigs. Insulin from animals is still available outside the U.S. — and cheaper than a recombinant DNA version.

Bettmann/Corbis

Dr. Jeremy Greene sees a lot of patients with diabetes that’s out of control.

In fact, he says, sometimes their blood sugar is “so high that you can’t even record the number on their glucometer.”

Greene, a professor of medicine and history of medicine at Johns Hopkins University, started asking patients at his clinic in Baltimore why they had so much trouble keeping their blood sugar stable. He was shocked by their answer: the high cost of insulin.

Greene decided to call some local pharmacies, to ask about low-cost options. He was told no such options existed.

“Only then did I realize there is no such thing as generic insulin in the United States in the year 2015,” he says.

Greene wondered why that was the case. Why was a medicine more than 90 years old so expensive? He started looking into the history of insulin, and has published a paper about his findings in this week’s issue of the New England Journal of Medicine.

The story of insulin, it turns out, starts back in the late 1800s. That’s when scientists discovered a link between diabetes and damaged cells in the pancreas — cells that produce insulin.

In the early 1920s, researchers in Toronto extracted insulin from cattle pancreases and gave it to people who had diabetes, as part of a clinical trial. The first patient was a 14-year-old boy, who made a dramatic recovery. Most others recovered as well. Soon, insulin from pigs and cattle was being produced and sold on a massive scale around the world.

Acids, alcohol and pancreatic tissue were separated, bathed and mixed in this laboratory of a 1946 insulin factory in Bielefeld, Germany. Chris Ware/Getty Images hide caption

toggle caption Chris Ware/Getty Images

Acids, alcohol and pancreatic tissue were separated, bathed and mixed in this laboratory of a 1946 insulin factory in Bielefeld, Germany.

Chris Ware/Getty Images

But for some, the early forms of the medicine weren’t ideal. Many people required multiple injections every day, and some developed minor allergic reactions.

Over the next few decades, scientists figured out how to produce higher-quality insulin, Greene says. They made the drug purer, so recipients had fewer bad reactions. They also made the substance able to last longer in the bloodstream, which led to more stable blood sugar levels and less frequent injections.

“All of these innovations helped to make insulin a little bit safer, a little bit more effective,” Greene says.

Then, in the 1970s, scientists developed a new technique they could use for insulin production, called recombinant DNA technology. It involves putting the human gene for insulin into bacteria, which then produce large quantities of the hormone.

Then, a funny thing happened, Greene says: “The older insulin, rather than remaining around on the market as a cheaper, older alternative, disappeared from the market.”

Greene says there’s no one reason that companies stopped producing the older animal versions, but they clearly felt it would not be profitable.

Dr. Kevin Riggs, a professor of medicine at Johns Hopkins and co-author of the new insulin study, says the newer, recombinant version of insulin may have had some advantages in terms of convenience and fewer side effects. But there was probably something else at work — doctors being influenced by marketing.

“A lot of time we get caught up in some of the hype,” Riggs says. “When a new medicine comes out and it has theoretical advantages, we buy into that and think newer is better.”

The company that made the new form of insulin, called Humulin, launched a large marketing effort aimed at doctors and patients shortly after its release.

But newer drugs aren’t always better, says Dr. Adriane Fugh-Berman, a professor of medicine and pharmacology at Georgetown University. That’s partly because drug companies don’t have to prove that a new drug is better than what is already on the market — they just have to prove that it’s not worse.

Insulin made via recombinant DNA technology in 2009. SIU/Visuals Unlimited/Corbis hide caption

toggle caption SIU/Visuals Unlimited/Corbis

Insulin made via recombinant DNA technology in 2009.

SIU/Visuals Unlimited/Corbis

“In government-funded studies that have compared older drugs to newer drugs, often older drugs come out looking better or equal to newer drugs,” Fugh-Berman says.

For example, some patients have found that animal-derived forms of insulin work better for them, she says. They cause less variability in blood sugar, and fewer episodes of hypoglycemia.

And while those older kinds of insulin are not available in the U.S., they are available elsewhere.

“In Canada, there actually is still an animal-derived insulin on the market, and that was really due to the efforts of consumer advocates,” Fugh-Berman says.

As the older versions have vanished in the U.S., newer versions have stayed expensive. The drug can cost up to $400 a month. Because of that high cost, many of the estimated 29 million people living with diabetes in the U.S. can’t afford it.

Some industry analysts expect insulin costs to fall in the future. That’s because the most recent insulin patents have expired, paving the way to more competition. The FDA has also decided to allow biosimilar versions of insulin onto the market. These are substances that act in a similar way to existing forms, but are not necessarily identical.

“But there’s concern that the cost savings will be nowhere near as robust as they have been with generic drugs,” Greene says.

“Rather than reducing costs by 80 percent, as many generics have done, they might reduce costs by 40 percent,” Riggs says.

Greene says the point of their recent study about insulin costs isn’t to simply blame the drug industry. “We do not believe that there is a conspiracy to keep insulin expensive,” he says.

Rather, he says, incremental improvements in the drug — and the disappearance of older versions, which aren’t as profitable — are more likely explanations.

Greene says innovations in insulin over the past 90 years have been significant. But, he says, it’s important to ask this question: “Do these innovations merit the loss of affordable insulin?”

For patients at his clinic who can’t afford insulin, Greene says, the answer is clear. A more affordable version is needed.

WASHINGTON — Fifteen years ago, a patient with diabetes might have paid $175.57 for a 20-milliliter vial of the long-acting insulin Humulin R U-500.

Today, he’d shell out $1,487 for the same tiny vial, according to wholesale acquisition cost data from Elsevier’s Gold Standard Drug Database.

It’s easy to cast blame on the drug makers: Just three pharmaceutical companies, all of them massive, global enterprises, control the vast majority of the $27 billion global insulin market: Sanofi, Eli Lilly, and Novo Nordisk. And they always have, virtually since the drug was discovered back in 1921.

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But a thorough review of the drug’s nearly 100-year history reveals a much more complicated story: one that makes it clear that the drug makers, their generic counterparts, doctors, and, increasingly, the Food and Drug Administration itself all share blame for the broken insulin market. And while there are a slew of ideas being floated for solving this problem — everything from seizing drug patents to capping how much people with diabetes can pay out of pocket for insulin — multiple policy experts told STAT that creating generic competition is likely the key to bringing costs down for the more than 7.5 million Americans who rely on the drug.

As Congress gears up to investigate the market — already, Sanofi will testify before the Senate Finance Committee next week and Rep. Diana DeGette (D-Colo.) has pledged to bring the big three companies before her Energy and Commerce subcommittee — it’s worth questioning whether there isn’t reason to call others, like generic manufacturers or FDA Commissioner Scott Gottlieb — to testify, too.

“Everyone is at fault, which makes it hard to figure out how to fix it,” Dr. Walid Gellad, who heads the University of Pittsburgh’s Center for Pharmaceutical Policy and Prescribing, told STAT.

Modern insulins mimic the insulin hormone that is normally produced by the pancreas, regulating the amount of glucose in a user’s blood. People with diabetes inject the product either because their pancreas doesn’t create insulin on its own, or because the body has become resistant to the insulin their body produces.

Exactly who discovered the drug first is controversial; even the Nobel prize awarded for its discovery has been called into question. The researchers honored, Frederick Banting and John J.R. Macleod, were just two in a team of researchers at the University of Toronto that eventually discovered how to use insulin to treat diabetes. And Banting publicly fumed that Macleod did not deserve the award over an assistant, Charles Best.

Banting sold the patent for the product to the University of Toronto for just $1, hoping that the product would be readily available, given how vital the discovery was to treating a once fatal condition.

Eli Lilly was the first drug maker to produce the product on a large scale; early versions relied on insulin from livestock like cattle and pigs. Since then, the three manufacturers have developed long-acting and slow-release variations, and a host of other products, some of which are now nearly identical to what the body produces on its own.

For most of the drug’s history, generic manufacturers had little interest in entering the market. The insulin market wasn’t nearly as lucrative as it is today. In 1999, for example, Eli Lilly sold $701 million worth of insulin in the U.S., according to SEC filings. In 2017, Lilly took in $2.6 billion for just two of its insulin products.

“Twenty years ago, many of these products were so inexpensive the investment value just wasn’t there for generics,” said David Gaugh, senior vice president of sciences and regulatory affairs for the Association for Accessible Medicines.

That began to change in the last decade, around the same time drug makers started to spike their prices. In 2008, Humalog, Eli Lilly’s best-selling and most expensive insulin product, grossed more than $1 billion in U.S. sales — 12 years after it hit the market. In 2017, Lilly sold $1.7 billion worth of the drug. The increased revenue in Lilly’s coffers was due largely to price increases, a fact Lilly admits over and over in its own annual reports to shareholders.

Today, there is just one copycat version of insulin — and it is manufactured by Eli Lilly. The product, Basaglar, copies a pricey Sanofi product, Lantus, that is the world’s top-selling version of insulin. It’s roughly 15 percent cheaper than Lantus.

There are other factors, too, that have deterred generics manufacturers that might otherwise have been interested.

Doctors are reluctant to prescribe older insulin products — the ones that are eligible for generic competition, according to the American Medical Association. That’s despite the fact that research shows that many people with diabetes respond just as well to older insulins, according to research published in the journal Diabetes Care. A 2014 study from the Institute for Clinical and Economic Review also found that there’s adequate evidence to suggest older insulins are just as effective as newer insulins for people with type 2 diabetes.

Dr. Kasia Lipska, an assistant professor of medicine at Yale, told STAT that prescribing older insulin is to “go against the tide.”

“This totally thwarts generic competition because if the off-patent drug is seen as already irrelevant, there is no impetus to invest in it,” Lipska said.

While even the American Medical Association acknowledged in a recent policy statement that “guidance and educational materials can help younger physicians become more comfortable with prescribing more affordable insulin alternatives,” some doctors maintain that they shouldn’t be blamed for the current insulin affordability crisis.

“When we first starting using Humalog and Lantus, the difference between the two in terms of cost were minimal, but there were modest differences in hypoglycemia,” Dr. Irl Hirsch, a professor of medicine at the University of Washington, told STAT. “Since cost wasn’t a big concern, how can one blame the physicians?”

Branded drug makers deserve a share of the blame for the concentrated market, too.

Their strategy for keeping generic competition at bay? Filing patents — lots of them. Each of the major manufacturers has hundreds of unexpired patents related to their products, the devices that deliver the drugs, and the methods for manufacturing them.

Sanofi, which manufactures Lantus, has been singled out in particular for allegedly repeatedly making small changes to its product to file for new patents. It has filed 74 patents on some version of that drug alone, according to I-MAK.

Sanofi battled Lilly over its Basaglar product, too, citing patent infringement — effectively delaying the drug’s attempted 2014 launch for nearly two and a half years while the two duked it out in court. And Mylan, which has developed another copycat for Lantus, has its own patent dispute with Sanofi, one that began in 2017. (Mylan’s product also hasn’t yet been approved by FDA.)

“Our scientists’ inventions are novel and nonobvious as recognized by the patents we have been awarded by the US Patent & Trademark Office,” Sanofi spokesperson Ashleigh Koss, told STAT. “By protecting our patented inventions, we are paving the way for the discovery of new medicines to address unmet medical needs.”

The fear of similar patent disputes may also be discouraging other generic manufacturers from considering less lucrative copycats, Gaugh, from the generics’ lobby, told STAT.

“There’s all types of patents that are involved,” AAM’s Gaugh said. “Whether it be process patents, manufacturing patents, device patents … packaging patents, labeling patents and trademarks, all those are different methods used to prevent .”

Right now, however, the biggest roadblock to a generic insulin may actually be regulatory.

Insulin regulation is messier than perhaps any other drug because of its science and its unique history.

Insulins are technically biologics, a label used to describe drugs or therapies derived from living cells and organisms. But policymakers in Washington didn’t have a framework for regulating biologic drugs and their copycat counterparts, biosimilars, until 2010, when Congress laid out the start of that framework in its Biologics Price Competition and Innovation Act. As part of that law, Congress said insulin — which had previously been regulated like any other drug — would be regulated as a biologic beginning in 2020.

Congress left the logistics of that transition up to FDA — and the agency’s transition plan wasn’t as flexible as generic makers had hoped, at least for encouraging a generic insulin.

The FDA’s policy decrees that any insulin application that’s still pending before the agency on March 20, 2020, will be rejected. Any applicant would then have to start over and reapply under a new biosimilar pathway.

Given the lengthy timeline for drug development — along with an uncertain and often timely FDA approval process — the hard stop in 2020 has made it dicey for drug makers to submit a potential generic insulin application for several years now.

Even companies who have insulin products in development and are ready to file their applications with the FDA are now waiting to apply until after 2020, given they want to avoid going through the time and money of applying in 2019, only to be rejected on the March 20, 2020, date, AAM explained to the FDA in March 2016.

“he policy is already having a devastating effect on current development programs for many important protein products, including insulins,” AAM wrote in its most recent letter to the FDA on the subject, adding that the policy “conflicts with the relevant statutes, is arbitrary and capricious,” words often used by companies to signal they will sue over a policy.

When it was first proposed, generic drug makers blasted the 2020 cliff, saying it would “impair patient access to affordable alternatives” to insulin and other drugs.

Gottlieb said at an industry conference in December that the FDA had “carefully considered all comments received on the prior draft guidance,” however, the FDA rejected the major change generic drug makers wanted: changing the FDA’s policy for drug applications pending before the agency on March 20, 2020.

“We are carefully considering steps for pending applications if they’re pending before March 20, 2020 to minimize disruption to development programs,” FDA spokesperson Lyndsay Meyer told STAT. “At this time, the agency anticipates that it will impact few, if any, applications.”

“Sponsors have known about this transition for a decade. They’ve had time to prepare,” Meyer added.

Multiple lobbyists and consultants STAT spoke with all agreed that the FDA has the ability to interpret the law in a way that doesn’t delay generic insulins. AAM has suggested that the FDA simply rely on the data included in any application already pending on March 20, 2020, and allow a sponsor to amend its application with any additional information that might be needed, given the application will now be considered by the FDA to be a biologic, not a drug.

“The opportunities for FDA to really expedite competition are huge,” said Gillian Woollett, a senior vice president at Avalere Health. “The opportunities to encourage sponsors are all available now. So what I don’t understand is why FDA and HHS are saying all the things they’re saying and they’re not doing the things they can do now that would actually promote competition.”

As lawmakers in both parties eye drug prices as a potential area for bipartisan consensus and collaboration, it’s evident that insulin is near the top of the congressional to-do list.

Three separate congressional committees have held hearings in the last two months on drug pricing, and at each, the issue of insulin affordability loomed large. Two committees have already launched investigations of insulin makers, and another plans to have an insulin maker testify later this month.

Lawmakers, too, are already weighing legislation to lower insulin costs. The Congressional Diabetes Caucus has proposed a sweeping package of proposals for increasing insulin affordability that includes a legislative proposal to require insulin makers to disclose how they set their prices and another that would direct the FDA to expedite review of lower-cost insulins.

“Who would believe that 100 years later there are only three manufacturers?” House Ways and Means Chairman Richard Neal (D-Mass.) said. “It’s pretty wild when you consider that.”

Ike Swetlitz contributed reporting.

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