The author is co-founder and board member of Independent Voices for Safe and Effective Drugs. She is also a member of the steering committee of the Therapeutics Initiative at the University of British Columbia.

I have had type 1 diabetes for 52 years and like so many other Canadians with this disease, I learned about the heroic scientists who discovered insulin on day one of my diagnosis.

Over the past year, the country has celebrated the moment when, 100 years ago, Banting, Best, Collip and McLeod discovered insulin — with the first successful experiment on a dog in November 1921, and the first treatment offered to a human, in January 1922. When the group assigned the patent for insulin to the University of Toronto for one dollar in 1923, Banting made a statement that became famous: “Insulin does not not belong. She belongs to the world. »

This credo guided the University of Toronto in developing a distribution strategy to ensure that no one company would have a monopoly on the manufacture and sale of insulin. Public and private manufacturers around the world have been allowed to produce insulin on the condition that they sell it as close to the cost of production as possible.

While I rejoice in the discovery of insulin, I am appalled at how modern pharmaceutical companies have tied their opportunistic maneuvers in the insulin market to the achievements of its co-discoverers. Canadians deserve to know the truth about how the pharmaceutical industry has driven up insulin prices, created a global oligarchy and increased the burden on those who need this lifesaving medicine.

The centenary should have been an occasion to examine the consequences for diabetics of the decision in the mid-1980s to privatize the legendary Connaught laboratories, where insulin was developed. Many Canadians may know that Connaught was one of the largest producers and distributors of vaccines in the world and that its privatization compromised our access to vaccines. But they are less likely to know that Canada no longer produces a single drop of insulin, neither for us nor for anyone else.

Today, we are completely dependent on three companies — Eli Lilly, Novo Nordisk and Sanofi — which dominate 95% of the global insulin market. Two of them pulled dozens of safe, effective and affordable insulin options from the Canadian market, not because they were unsafe — they weren’t — but because they didn’t cause the profits that pharmaceutical company investors were hoping for.

And there is no guarantee that global producers will continue to supply insulin to Canadians. In 1985, Eli Lilly was the only insulin producer in Argentina when the country was going through a serious economic crisis. Faced with inflation rates above 800%, the government implemented price controls on all products, including medicines. In response, the company closed its factory, resulting in a sudden shortage of insulin for 73,500 men, women and children.

Eli Lilly, like Sanofi and Novo Nordisk, has also been involved in a vigorous and aggressive campaign to overturn our own system of protecting Canadians from unfair prices for patented medicines. In particular, she threatened to withhold or delay the introduction of new drugs in Canada. Yet tighter price controls are exactly what people who use insulin need.

We have become more, not less, vulnerable since Connaught was privatised. Health Canada cannot be relied upon to protect access to insulin because—unbelievably—the department claims to have no mandate for manufacturers to supply Canadians. It was this position that enabled the withdrawal of the entire line of less expensive animal insulin developed by Connaught. This was replaced by biosynthetic human insulin (BHI), which manufacturers touted as an innovation on the same scale as the original 1921 discovery.

Introduced in 1983 in North America and Europe by Eli Lilly and Novo Nordisk, human insulin was the world’s first product derived from recombinant DNA technology. But many believe that, rather than providing a necessary addition to the panoply of diabetes drugs, the pharmaceutical industry saw insulin as an ideal vehicle for testing gene cloning, not least because it was a very large and captive market. And, given the high levels of public anxiety at the time, biotechnology needed a respectable ambassador.

When BHI was submitted for approval by regulatory agencies such as the US Food and Drug Administration and Health Canada, the manufacturers claimed that it was virtually interchangeable with porcine insulin. Both regulators approved new insulin products in a record 5 months, compared to the average approval time of 40-60 months. FDA Medical Review Officer Henry Miller maintained that “the quality of Lilly’s submission was unparalleled and the evidence for safety and efficacy was unequivocal and abundant.”

The highly respected Cochrane Collaboration was less impressed. In 2002, the group noted that the studies – 70% sponsored by manufacturers – were of “poor methodological quality” and failed to take into account key parameters such as mortality, morbidity and quality of life related to health. Evidence, gathered in trials lasting five to six months, showed that BHI had no therapeutic or clinical advantage over animal insulins and that only 40% of studies provided information on adverse effects . And while Miller called the FDA approval a “historic event,” Cochrane concluded that the introduction of human insulin should serve as an example of “pharmaceutical and technological innovations that are not supported by evidence.” sufficient of their advantages and safety”.

While telling regulators that BHI was as safe and effective as animal insulin, manufacturers were telling the public that human insulin was identical to the insulin produced by non-diabetics — almost a cure. A representative of Eli Lilly, when asked by a reporter about the superior benefits of human insulin, responded rhetorically, “What would you like to inject, something human or something from a pig?” »

For the pharmaceutical industry, the BHI was a gold mine, increasing profits beyond what one could have imagined. Today, the average cost of producing insulin is about $5 per 10ml vial, but most people in Canada pay $35 to $80 (in the US it’s up to $380). The situation is even worse in the countries of the South. It is currently estimated that half of the people who need insulin cannot afford it, which is a death sentence for people who have to go without. Children like Leonard Thompson, Banting’s first patient, are still dying from lack of insulin in low- and middle-income countries. For these children, it is still 1921.

The pharmaceutical industry argues that this is the cost of innovation and that the higher prices are because insulin is safer or better than it was 30 or 40 years ago when it cost less than a third of what it costs now. Yet insulin now ranks second among drugs for which serious but non-fatal side effects have been reported. One of these side effects — hypoglycemia — is a leading cause of visits to hospital emergency departments among people with diabetes.

Hypoglycemia is the term used to describe low blood sugar, the most common side effect of insulin therapy, regardless of the type or species of insulin. When a person’s blood sugar is too low, the body releases hormones that send warning signals to the brain. The absence or weakness of these signals are major risk factors for severe and even fatal hypoglycemia.

Shortly after the introduction of BHI, diabetics began to report that their warning signs of hypoglycaemia had weakened or disappeared. A 1991 report in the UK documented unexpected overnight deaths in young otherwise healthy diabetics who had been switched to BHI, a tragedy described as ‘death in bed syndrome’. Insulin makers have changed their product labels to emphasize that switching from animal insulin to human insulin may result in weaker hypoglycemia signals in some. During his appearance before Canada’s Standing Committee on Health in 2003, Eli Lilly admitted that a few long-time diabetic patients had suffered from a condition called “unperceived hypoglycemia” when switched to biosynthetic human insulin.

Today, studies indicate that up to 50% of people using biosynthetic human insulin are unable to safely detect hypoglycemia, and young children detect no more than 40% of these episodes. A 2018 study found that diabetics whose condition required an ambulance were twice as likely to have impaired awareness of hypoglycemia, a frightening reality especially for children and parents.

Lack of awareness of hypoglycaemia and other problems associated with biosynthetic human insulin was the subject of three attempted class actions in the UK, USA and Canada between 1992 and 2004. One d’elles was started by a woman who claimed to have experienced excruciating pain in response to Humulin insulin manufactured by Eli Lilly. In an obscure 1988 report, one of the company’s scientists described a “syndrome consisting of arthralgia, arthritis, myalgia, increased erythrocyte sedimentation rate, and mild normochromic anemia or hypochromic without change in serum complement or haematuria… All cases responded to discontinuation of treatment with human insulin”.

How has the industry reacted to these issues? Instead of ensuring diabetics have access to a wide range of insulin options, manufacturers have removed animal insulin, the only safe option for about 10% of people who need this treatment. They partnered with device makers, resulting in an industry producing technological solutions, each with their own risks and costs — insulin pumps, glucometers, pens and other expensive high-tech instruments, most of which are necessary to mitigate the risks associated with insulin therapy.

People who need insulin deserve better than this. Health Canada, in response to requests from people with diabetes who use insulin, has worked to ensure the continued accessibility of animal insulin products in Canada.

The best way to do this is to bring the production of insulin, both animal and biosynthetic, back into the public domain, and increase the range of safe and effective options while removing financial barriers to access. This was the plan in 1921, and it is worth celebrating and fighting for today.

#murky #history #insulin