A Harvard Medical School scientist’s experiments with fish discarded along the coast near Boston have led, 20 years later, to a new class of diabetes drugs. The latest, from Novartis AG, may get US approval this week.
In 1987, Joel Habener, then a research physician at Massachusetts General Hospital, discovered a protein in the pancreas of anglerfish that is alsocritical to humans.
Five drugmakers, including Merck & Co., Eli Lilly & Co. and Novartis, have used Habener’s findings to create medicines doctors say may revolutionize diabetes treatment.
Lilly’s Byetta was approved in the US last year. It’s now an increasingly popular treatment that generated $126.4 million (Rs556.16 crore) in third-quarter sales, a 28% increase from the second quarter. In November, Merck began selling its version, called Januvia, and Novartis expects its drug, Galvus, to gain US approval soon, perhaps as early as Wednesday.
“It’s going to be the most interesting marketing battle we have seen in Big Pharma in quite a while,” said Les Funtleyder, a New York-based analyst with Miller Tabak & Co. Galvus and Januvia each may get $1 billion in annual revenue, he says, matching estimates on Byetta.
The drugs mimic the action of Habener’s protein, an intestinal molecule that tells the pancreas to produce insulin, a hormone that helps cells turn sugar into energy. People with diabetes either don’t produce enough insulin or aren’t able to use what they have. Without insulin, cells can’t properly process glucose, or blood sugar.
The new drugs are designed to treat Type 2 diabetes, the most common form of the disease. According to the World Health Organization, about 180 million today are diabetic, and the number is likely to more than double by 2030.
New treatments are needed because the existing ones have side effects, said James Shannon, head of research and development at Novartis, which is based in Basel, Switzerland. Drugstore.com
The older drugs include metformin, sold in generic form by several companies, and Actos, from Lilly and Takeda Pharmaceutical Co. of Osaka, Japan.
Lilly shares rose 7 cents to $54.67 in New York Stock Exchange trading on Monday, and have fallen 4.7% since 3 January 2006. Novartis shares rose 35 centimes to 73.2 francs in early Zurich trading, and have gained 4.2% this year.
In animal studies, the latest drugs, known as DDP-4 inhibitors, also have slowed progression of the disease.
If similar results are found in humans, the drugs may delay patients’ need to take insulin shots. About 21 million people in the US, or 7%, have diabetes, according to the American Diabetes Association.
“The diabetes market has large potential because it’s growing and because existing treatments are not optimal,” Funtleyder said.
The $15 billion spent worldwide on diabetes treatments is expected to grow to $25 billion by 2011, he said.
In the late 1970s, Habener, a doctor specializing in diabetes care, began buying fish deemed “trash” from the brother of a fisherman working his way through school by selling fish organs to research labs. Habener was curious about the way animals control blood sugar. By 1987, he had identified a previously unknown protein he called glucagon-like peptide-1, or GLP-1, that stimulates the pancreas to produce insulin.
While Habener remembered thinking “this could be interesting,” he also said he realized the substance would never be a useful pill. The protein was so delicate that an oral version of it would be destroyed by stomach juices before it could get carried into the bloodstream and on to pancreas cells.
In 1992, John Eng, a doctor at the Bronx Veterans Affairs Medical Center in New York, moved the research forward when he found a molecule in the saliva of Gila monster lizards that was similar to Habener’s GLP. Amylin Pharmaceuticals Inc., a small San Diego, California-based biotechnology company, licensed Eng’s molecule, which the company eventually developed into Byetta, now sold by Lilly.
Byetta lowers blood sugar levels by stimulating the pancreas to produce insulin. When the body has too little insulin, sugar backs up into the bloodstream, damaging the kidneys, eyes and nerves.
In 1995, a team of Danish researchers uncovered still another route to using Habener’s discovery to treat diabetes. The scientists found an enzyme that naturally digests GLP. By blocking the enzyme, they could increase the body’s reserves of GLP, thereby raising insulin levels.
Just weeks later, Novartis researchers began searching for drugs that could block the enzyme, called DPP-4, to increase GLP supplies and insulin.
“It was like a lightning bolt had rumbled through the department,” said Edwin Villhauer, a Novartis chemist who led the search for a diabetes drug. Villhauer, who works in Novartis’s East Hanover, New Jersey, labs, remembers screening at least 2,000 compounds. The finding set off a race among Byetta and the DPP-4 inhibitors, including Januvia and Galvus.
While other companies are rushing to develop their own DPP-4 inhibitors, there is evidence that treating diabetes though the GLP pathway is effective. The first drug in the class, Lilly’s injectable Byetta, is gaining wide use because it helps patients lose weight, a common concern for diabetics, doctors say.
Barry Kittredge, 59, an assistant high school principal in Haverhill, Massachusetts, said Byetta had allowed him to shed 25 pounds (11 kilograms) since he started injecting the drug nine months ago. Kittredge said that since taking Byetta he feels full after eating less food.
“It has really cut my appetite for doughnuts,” Kittredge said.
Kittredge, who also takes daily insulin shots and pricks his own finger to get a reading on his blood sugar levels, said injecting Byetta is not a big ordeal.
“Byetta is much easier to inject than the insulin,” said Kittredge, who describes himself as “the world’s biggest coward.” The therapy requires him to use a small pen-like needle twice a day that is less painful than injecting insulin.
Executives at Merck and Novartis say they believe their oral drugs may prove more popular than Byetta. Neither Merck’s Januvia nor Novartis’s Galvus has shown in patient studies to be more effective than metformin, an older medicine that sells for as little as $4 for a 30-day supply at Wal-Mart. The companies say more studies may show the new drugs are superior.
In patient trials, Galvus pushed blood sugar levels as low as Avandia, an older drug sold by GlaxoSmithKline Plc that is similar to Takeda’s Actos. The FDA was scheduled to rule on Galvus in November and extended its review for three months in order to evaluate additional safety data from the company.
While analysts say they expect Merck and Novartis to compete for market share, other drugmakers are looking to secure some of that market for drugs that are not yet approved. In January, London-based AstraZeneca Plc agreed to pay Bristol- Myers Squibb Co. of New York as much as $1.35 billion for rights to develop and market still another DPP-4 blocker.
Habener, the Harvard doctor who first found GLP-1, has his hopes aligned with a drug dubbed liraglutide, made by Bagsvaerd, Denmark-based Novo Nordisk A/S. While the drug, like Byetta, is similar to the molecule he found, it’s the only one on which his employer, Massachusetts General Hospital, holds a patent.