In 1921, University of Toronto scientists discovered insulin, the pancreas-produced hormone that breaks down sugar in the blood. They quickly purified it, injected it into children dying from Type 1 diabetes, and were hailed as the first great miracle-makers of modern medicine.
There have been many improvements to animal-derived insulin over the years. In 1982, the Food and Drug Administration approved the first DNA-based human insulin. Short- and long-acting biologic insulins were approved in 1996 and 2000, respectively.
All the patents expired years ago. Yet, nearly a century after the initial discovery, the 7.5 million patients who rely on insulin—about a quarter of U.S. diabetics—still don’t have a generic alternative.
That regulatory failure has enabled the three major manufacturers of insulin to set exorbitant prices on their life-saving products. Eli Lilly’s best-selling Humalog’s price rose 700% between 2001 and 2015; Novo Nordisk’s Novolog and Sanofi’s Lantus nearly doubled from 2013 to 2019.
Those price hikes have been disastrous for cash-strapped patients. A recent report from the Congressional Diabetes Caucus reported the tragic case of 26-year-old Alec Raeshawn Smith, who died in 2017 after rationing his insulin because he could not afford his insurance company’s co-pays.
Why didn’t Alec have access to lower-cost generics? Though Congress passed the Biologics Price Competition and Innovation Act in 2009, it wasn’t until earlier this month that the FDA finally issued a general guidance on what tests will be required to validate a generic alternative as interchangeable with brand name biologics at local pharmacies.
Agency scientists are now mulling whether insulin will qualify for a more limited set of tests to establish interchangeability. Limited testing—the equivalent of a Phase 1 safety trial at the FDA—is critical if generic insulins are to come to market at much lower prices.
In the handful of instances where the FDA has approved biosimilars (the brand-name industry’s preferred term), the agency required not just extensive safety tests but efficacy testing. None have been approved as interchangeable with a branded medicine.
Efficacy testing without interchangeability gives generic biologic makers incentives to price their products near their branded rivals. They are more like “me-too” small-molecule drugs, which are aimed at divvying up market share, not lowering costs.
At an FDA hearing held last week, an Eli Lilly representative pushed for extensive testing for generic insulin to establish interchangeability. The FDA should “consider using an efficacy primary endpoint,” said Dr. Sherry Martin, the company’s associate medical director for endocrinology.
Dr. Jing Luo of the medicine department at Brigham and Women’s Hospital challenged the industry’s position. Medication switches between branded products are already common, he said.
The Lilly representative also raised objections because insulin will soon be delivered by diabetes management systems that use continuous glucose monitoring, embedded pumps and cloud-based, electronic controls. “Interchangeability for biosimilar insulins within a connected ecosystem should be assessed separately,” she declared.
In other words, insulin makers are already erecting the next set of barriers to entry in their exclusive market. “This is the first time I’ve heard about the ecosystem,” said Christine Simmon, executive director of the Biosimilars Council at the Association for Accessible Medicines, the generics industry trade group. “In an ecosystem where things are patented, we know that patent thickets and overpatenting are a big barrier to biosimilar adoption.”
By law, the FDA must only consider science when making its decisions, not economics. Those backing limited testing to establish generic insulin interchangeability have shown that good science and low cost can coincide.