Jackie Chaline was diagnosed with diabetes 16 years ago, but even after seven years of insulin therapy the 66-year-old Frenchwoman isn’t used to the sometimes painful regimen of four injections a day that keeps her alive. When Chaline eats out, she ducks into bathrooms to spare others the sight of the needle. She also has to rotate between her arms, belly, and thighs to find undamaged skin to prick. “Swallowing a tablet would make such a difference,” says Chaline, who has taken about 9,000 insulin shots in the past seven years.
Novo Nordisk (NVO) hopes to provide one. The Danish company is spending at least $2 billion to make a pill hardy enough to cheat the body’s own defense mechanisms and deliver long-acting insulin to the bloodstream. “The odds of making it were a million to one five years ago,” says Chief Science Officer Mads Krogsgaard Thomsen. “Are we getting closer to a 50-50 scenario? Absolutely.”
If successful, an insulin pill could generate sales of $5 billion to $10 billion a year, estimates Vincent Meunier, an analyst at Exane BNP Paribas in Paris. “It would be one of the biggest drugs of all time,” he says, adding that for now it’s still “in the realm of science fiction.”
Diabetes, caused by a lack of insulin needed to convert blood sugar into energy, affects 366 million people worldwide, killing one every seven seconds and incurring annual health-care costs of $465 billion, the International Diabetes Federation estimates. Left untreated, it can lead to kidney damage, blindness, heart problems, or death.
Many diabetics must inject insulin multiple times daily to prevent sugar from pooling in their blood. A pill wouldn’t replace injections entirely, because it’s likely to be used only in patients whose bodies can still produce some insulin. Instead, the drug would allow diabetics to get treated earlier because doctors wouldn’t wait to prescribe a pill as they do with injections. “If this were to work, it would be huge,” says Spyros Mezitis, an endocrinologist at Lenox Hill Hospital in New York. “We would get more people on insulin.”
So far, Novo’s experimental insulin pill has been tested on rats, dogs, and more than 100 human volunteers. One version, dubbed NN1953, has successfully completed a first round of clinical tests, in which people took the tablet once, Novo said in February. It wouldn’t comment further on the tests.
Chief Executive Officer Lars Sørensen kicked off the pill hunt six years ago. Novo, the world’s biggest insulin producer, needs new products to go against diabetes treatments from Eli Lilly (LLY) and France’s Sanofi (SNY). The Danish company is waiting for U.S. regulators to approve a long-acting injectable insulin, degludec, intended to wrest share from Sanofi’s best-selling Lantus.
When swallowed, insulin embarks on a journey through the stomach and the intestines, where it faces the assault of acids and enzymes. It must then cross the gut wall, usually accessible only to smaller particles known as amino acids, to reach the bloodstream and travel to the liver.
To do that, Novo has been bringing together its scientists, experienced in insulin engineering, and external researchers who are expert in tablet formulation. New hires include Nazaneen Pourkavoos, who helped develop Merck’s (MRK) extended-release pill. Pourkavoos, whose role is to find a formulation that can cross the gut barrier, works with Thomas Kjeldsen, a 23-year Novo Nordisk veteran who likes to carry the experimental tablet around like a baby—and speaks of it in the same adoring tone. “This is the real thing,” he says, holding up the oval white pill prototype. “You think about the insulin pens, the needles, and then you look at this. It explains all the efforts.”
Novo also must extend the hormone’s ability to stay in the bloodstream (which its scientists think they’ve solved) and boost its capacity to be absorbed by the body (which they have not).
Novo will know which of its oral insulin candidates is ready for mid-stage clinical development by late 2013, Thomsen says. Even if it’s successful, Novo could face difficulties of a different kind. An insulin pill may be “cannibalistic of their existing business,” says Alistair Campbell, an analyst at Berenberg Bank in London. Still, “the risk is someone else could develop a pill, so the fact they are leading the way on oral insulin is, from a defensive point of view, good news for them.”