Oramed Pharma and Novo Nordisk in race to bring out oral insulin, which is expected to hit market by the end of the current decade

An insulin pill, long desired by diabetes doctors and patients but abandoned as not physically viable, could be available by the end of this decade as a tiny Israeli company races a Danish pharmaceutical giant to be first with what could be a multibillion–dollar product.

In the pharma industry’s equivalent of a David and Goliath story, the companies at the forefront are Novo Nordisk, the world’s largest seller of insulin products with a market value of about $74 billion, and Oramed Pharmaceuticals Inc, with a market value of only $50 million and headquartered in Jerusalem, where the biblical David held court.

The concept of oral insulin as a way to relieve people with type 1 diabetes of several daily injections has been around since the 1930s. It was left for not pursued because as a protein composed of amino acids, insulin is destroyed by enzymes in the digestive system before it can do any good.

While scepticism over a viable insulin pill remains high, Novo and Oramed believe they have come up with solutions that will allow enough insulin to survive the onslaught of digestive juices.

"We’ve built technologies and we’ve seen from studies in animals and early human trials that this may not be as impossible as decades of research had indicated previously," said Peter Kurtzhals, Novo’s head of diabetes research.

High levels of insulin circulating in the body, other than digestive system, may raise risk

If all goes well, Novo believes its oral insulin could be available by the end of this decade or early next decade.

Oramed's program is ahead of Novo’s. It has begun enrolling patients in Phase II, or midstage clinical trials, while Novo has yet to begin Phase II testing.

The brains behind Oramed’s oral insulin is the chief executive’s mother, Miriam Kidron, who laid the groundwork with years of diabetes research at Hadassah–Hebrew University Medical Center. "She’s the chief scientist. "I just went for the ride to do the business side," said Oramed CEO Nadav Kidron.

"My mother said it could be commercial but Hadassah won’t be able to fund it," Kidron recalled. "I took the IP from Hadassah and started Oramed. Since then, we’ve been moving it forward."

Regardless of who wins the race, Kidron said, "there must be an oral insulin. This is going to be a huge market." He sees the market potential to be at least $7 billion a year. Novo said this week the global market for diabetes tablets could be worth more than $18 billion a year.

That is because the focus for oral insulin has shifted to the ballooning health crisis of type 2 diabetes, a progressive disease often caused by obesity. An estimated 90 to 95% of more than 370 million people living with diabetes worldwide suffer from type 2, according to the International Diabetes Federation. It projects that could climb to 552 million by 2030. GBI Research forecast the global market for type 2 diabetes treatments reaching nearly $40 billion by 2019.

"Even though there are other anti–diabetic agents and more coming in, ultimately all (type 2) patients with diabetes, if they live long enough, will need insulin," said Novo's Kurtzhals.

There is still a long way to go for Nova or Oramed to receive regulatory approval. The companies must prove the worth of their oral preparations with large clinical trials and demonstrate no heart problems or other major side effects.

Other than injections, no other insulin preparations have been shown to be satisfactorily safe and effective, doctors said. Past failures of alternate delivery systems include Pfizer Inc’s abandonment in 2007 of its inhaled insulin product. "I’m not going to hold my breath on this one," said Dr Robert Ratner, chief science and medical officer for the American Diabetes Association (ADA).

"It would be an important contribution to the therapeutic armamentarium. But there are still great limitations in our ability to get the insulin absorbed and control how much insulin gets absorbed," Ratner said.

Other treatments being tried include nasal spray and a skin patch, which lack some of the potential advantages of an oral insulin.

A More Natural Approach

Insulin injections were introduced commercially as a life–saving treatment for diabetes in 1923 by Eli Lilly and Co. Novo has also sold insulin products for around 90 years. While insulin is naturally produced in the pancreas and then goes to the liver, injected insulin circulates throughout the body before it gets there. The main attractiveness of an insulin pill, if it works, is that any absorbed insulin would go directly to the liver from the digestive tract.

"It is a much more natural physiological approach," said Dr. Joel Zonszein, director of the Clinical Diabetes Center at Montefiore Medical Center in New York. Some doctors believe high levels of insulin circulating through the rest of the body may increase health risks.

Since the digestive system can break down insulin in a matter of seconds, both Novo and Oramed’s approaches for their insulin pills involve protective coatings and molecular tweaks or added ingredients to help enough insulin be absorbed to provide effective glycemic control. That involves giving large enough doses of insulin so that some 90% can be destroyed without sacrificing efficacy.