There are 21 million people living with diabetes in the U.S., six million of whom take insulin. Although insulin has been used as the life-saving drug of choice to control diabetes for nearly 100 years, generic insulin has yet to be seen on the market.
As a result, uninsured diabetes patients in the U.S. must shell out between $120 and $400 per month for brand-name insulin, a hefty price tag compared to the $4 price tags carried by the generic versions of many other essential medications. A recent study conducted by the Hopkins School of Medicine looked into a simple question: Why doesn’t generic insulin exist?
A “generic drug” refers to any drug marketed under its chemical name without advertising. Generics are usually not associated with any particular company and are typically sold at significantly lower prices than their brand-name equivalents. In most cases, when a drug developer’s patent for a particular drug expires, the drug can be produced as a generic.
This increases competition among manufacturers of generics, which drives down the price of the drugs.
In 1921, Frederick Banting and Charles Best discovered that they could extract active insulin from whole animal pancreases to treat diabetes. In 1923, the two young scientists sold their U.S. patent for insulin to the University of Toronto for $1; once their method of insulin extraction was published, anyone would be free to prepare the medication, but no one would be able to secure a profitable monopoly.
It wasn’t long before pharmaceutical companies — such as Eli Lilly and Denmark’s Nordisk Insulinlaboratorium, which later merged with Novo Terapeutisk Laboratorium to form Novo Nordisk — began devising substantial upgrades for Banting and Best’s initial formula for insulin.
In the early 1930s, researchers at Nordisk found that adding protamine to insulin prolonged its action, which allowed diabetes patients to take fewer insulin injections per day. In 1946, researchers discovered that adding zinc to insulin with protamine made it possible for many patients to be treated with a single daily injection. In the 1950s, lente (“slow”) insulins were developed to prolong the action of insulin without adding protamine. While these innovations expanded the options for insulin dose adjustment, they also extended insulin patents into the 1970s.
Even with these innovations, insulin was still far from perfect. At the time, insulin was typically extracted from cows or pigs, which meant that impurities associated with animal tissue extracts frequently caused immunological reactions in humans and reduced the efficiency of insulin medications. In the 1970s, Novo and Lilly both spearheaded improvements to the insulin manufacturing process, which helped to increase insulin purity and reduce side effects. While these innovations boosted the safety of insulin medications, they also extended insulin patents into the late 1980s.
In 1978, researchers at Genentech pioneered an original method of producing human insulin through genetic recombination technology. Using this technology, Lilly developed and introduced the first recombinant human insulins — Humulin R, short-acting, and N, long-acting — to the U.S. market in 1982. In 1988, Novo Nordisk introduced human insulins that were synthesized from chemically converted beef insulins. The novel developments of Genentech, Lilly and Novo Nordisk resulted in a plethora of insulin patents that extended into the 21st century.
Today, the most recent insulin patents have expired. So why is insulin still unavailable in generic form? One major reason is the presence of biosimilar insulins on the market.
For large-molecule biological drugs such as insulin, it is impossible to know whether one drug is the same as another on an atom-by-atom basis. Therefore, even the with the most minute changes, such as a single amino acid substitution, a pharmaceutical company can obtain a new patent for insulin. These insulins are referred to as “biosimilars,” officially approved versions of original “innovator” products. Pharmaceutical companies can develop and manufacture biosimilars under their own brand name once the original product’s patent expires.
The development of successive biosimilars is an example of “evergreening,” the process by which a series of incremental improvements to a drug can extend a company’s patent for the drug for several decades. Nearly a century of “evergreening” by various pharmaceutical companies has prevented generic versions of insulin from becoming available.
Of course, many early improvements to insulin were critical to improving the efficiency, flexibility and safety of insulin. It goes without saying that insulin today is significantly safer and more convenient to use compared to the early 20th century incarnations of the drug. However, regarding more recent versions of insulin, there is currently no scientific evidence to show that human insulin produced using recombinant technology is clinically superior to the best, purest available animal-extract insulins.
However, with the advent and popularization of brand-name human recombinant insulins, purified pork and beef insulins did not spur a market for generic competition. Instead, they were rendered obsolete and are currently unavailable for human use in the U.S. This is because generic-drug companies do not feel it is worthwhile to invest in the additional manufacturing practices required to produce high-quality versions of already-obsolete pork or beef insulin. Instead, many generic-drug companies opt to produce off-patent small-molecule drugs such as aspirin, which generally requires less effort and is often more achievable.
Unfortunately, the resulting absence of generic insulin from the market means that many diabetes patients, especially those without insurance, cannot afford the high price of insulin, which leads to devastating medical complications for patients as well as disastrous consequences for health care systems.
When Banting and Best sold their insulin patent for $1 in 1923, they specifically stated that their goal was not to make a profit off of their discovery, but rather to ensure that diabetes patients could obtain quick and safe access to insulin. If Banting and Best were alive today, one can imagine how disappointed they would be to witness pharmaceutical companies continuing to squeeze as much revenue out of insulin as possible, leaving patients who cannot afford the lofty prices of brand-name insulin to suffer the consequences.
