An oral agreement

BAGSVÆRD, Denmark—Novo Nordisk AS made the news recently when Chief Scientific Officer Mads Krogsgaard Thomsen gave interviews to Danish business newspaper Borsen and other media outlets in early October and told them that the company would spend some $3.65 billion between now and 2020 developing diabetes tablets that could replace traditional insulin injections—this includes six diabetes pills already under development and potential future production facilities. He estimates that the global market for diabetes tablets could be worth more than five times that investment annually as the next decade begins.

News of Novo Nordisk’s capital injection—to replace or reduce the need for injections—also brought concurrent media attention to Israeli company Oramed Pharmaceuticals Inc., a rival in the goal of producing oral insulin; however, its corporate profile is more modest with a market value of $50 million compared to Novo Nordisk’s $74 billion.

Jerusalem-based Oramed does have the distinction of having reported in August of this year, a month-and-a-half before Novo Nordisk’s latest pronouncement, that it has initiated patient recruitment for a new clinical trial of its orally ingestible insulin capsule, ORMD-0801, for patients with type 1 diabetes in Israel.

According to Oramed, prior clinical studies have shown that ORMD-0801 administered to patients with type 1 diabetes just prior to a meal effectively kept their blood sugar levels stable. The results of one such trial were published earlier this year in the journal PLOS ONE in an article titled, “Glucose-Reducing Effect of the ORMD-0801 Oral Insulin Preparation in Patients with Uncontrolled Type 1 Diabetes: A Pilot Study.”

Another distinction for Oramed is that it has now reached the point of Phase II clinical trials with ORMD-0801—unlike Novo Nordisk, which still hasn’t progressed past Phase I with any oral insulin candidates.

As Oramed CEO Nadav Kidron told Reuters in early October, plans are for his company to take its oral insulin through Phase II testing and then find a larger partner to fund Phase III trials and beyond, adding that there is no shortage of potential partners among Japanese companies, U.S. companies and others, or even Novo Nordisk itself. As Kidron was quoted as saying: “Novo is in a different league from anyone else out there. I look up to them.”

October’s nearly $3.7-billion announcement isn’t the first time Novo Nordisk has talked about major investments in the race toward oral insulin, though it’s the biggest number bandied about so far. In 2012, speaking with a reporter for Bloomberg, Thomsen said Novo Nordisk was committing at least $2 billion to make an insulin pill that would be tough enough to survive the digestive system and still deliver insulin to the bloodstream.

“The odds of making it were a million to one five years ago,” he told Bloomberg at the time. “Are we getting closer to a 50-50 scenario? Absolutely.” Of course, those previously long odds were precisely why the company had nearly abandoned diabetes pills some six years ago to focus on better formulations of injectable insulin and better ways to deliver it.

Thomsen also noted that a tablet to deliver insulin would not likely be a replacement for injected insulin. Instead, it would more likely be used for patients who still have some ability to produce insulin but who might delay insulin therapy because they don’t want injections, and thus increase pressure on the pancreas and increase the likelihood of major health problems later.

Asked what has changed now to increase the funding commitment and what continues to drive the quest for oral insulin despite the many failures in the past with alternatives to injection, Peter Kurtshals, senior vice president and head of insulin research at Novo Nordisk, tells DDNews, “We are engaged in these programs because we believe that oral insulin and GLP-1 would meet a patient need. For example, in surveys doctors mention that insulin is often initiated later than it should in people with type 2 diabetes because of the complexity and stigma related to the injection. Therefore, we believe that making insulin orally available could lead to better treatment of people with diabetes. Secondly, we are encouraged by the progress we have made on technologies and the data we have seen in animals and in early trials in humans.”

Asked to explain what differentiates Novo Nordisk’s approach from Oramed, Kurtshals says, “Novo Nordisk’s oral insulin program is focused on developing a long-acting basal insulin in a tablet, specifically targeting the largest insulin segment and the type of product needed for insulin initiation. Other companies, including Oramed, seem to be focusing on short-acting insulin, which is to be given in connection with meals. This would likely be harder to do in a reproducible manner due to the potential interference between ingested food and absorption of the insulin.”

Oramed had not responded to requests for an interview as of the time this issue went to press.