(Source: Reuters)
New treatment is badly desired as global diabetes rates soar

Aside from certain insects, all members of the animal kingdom require the peptide hormone insulin to regulate carbohydrate and fat metabolism -- and humans are no exception.  Diabetes -- an inherited or acquired disease in which a human's pancreas stops producing insulin -- was one of the first diseases known to man.

I. New Millennia, Same Old Diabetes Treatment

In 1921, having recognized that insulin regulated sugar metabolism, medical doctors began to obtain and purify insulin from various animal sources -- cows, pigs, horses, or even fish -- and injecting it into patients as a life-saving treatment for diabetes.  By the 1970s, purities of "99%" had been reached and production was dominated by large pharmaceutical companies.  In the 1980s, Eli Lilly and Comp. (LLY) became the first company to produce insulin from a non-animal source, using genetically engineered E. coli bacteria.  Other companies soon followed in suit.

But while the methods of production and impurity have improved -- and some new preventive therapies are on the horizon -- the treatment of diabetes still relies on the same unpleasant method of drug delivery -- an injection.  Pharmaceutical companies long believed this was the only way, as attempts to produce an "insulin pill" proved fruitless.

Insulin Injection
Diabetics today are treated the same way as they were in 1921, more or less -- with insulin injections. [Image Source: Wikimedia Commons]

The key technical challenge is that any pill to deliver insulin must survive a slew of digestive enzymes and the stomach's highly acidic environment.  The stomach naturally produces pepsin, and it "imports" trypsin/chymotrypsin from the pancreas.  All of these enzymes break down polypeptides -- a group of chemicals that produce insulin.  So surviving the stomach is one daunting obstacle.  And even if an insulin pill could survive, it would have to be able to selectively dump its contents once it reaches the small intestine.
Insulin is a polypeptide, which makes it vulnerable to digestion by the stomach.
[Image Source: Wikimedia Commons]

Dr. Robert Ratner, chief science and medical officer for the American Diabetes Association (ADA), in a recent Reuters interview, remarks, "I'm not going to hold my breath on this one.  [An insulin pill] 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."

II. Novo Believes in Diabetes Pill

But now one top drug maker -- and a small startup -- believe that an insulin pill is not only possible, but will be produced by the end of the decade.

On the corporate side Denmark's Novo Nordisk (OMX:NODO-B) has been the first company to publicly express a conviction that an insulin pill is possible.  Novo Nordisk has been experimenting with the concept in its labs for seven years now, and says that such a pill may be commercially available by the end of the decade or early next decade.

Diabetes pills
A batch of experimental insulin pills is finished at a Novo Nordisk lab. [Image Source: Bloomberg]

Internally Novo Nordisk refers to the hunt for an insulin pill therapy as a "holy grail" quest, indicating that it understands the difficulty and risk.

Novo Nordisk is building its attempt at this challenge upon new methods that allow insulin pills that survive the stomach and then route their contents from the small intestine to the liver.  The approach requires a lot of extra insulin as up to 90 percent is destroyed in transit.  Aside from the feasibility of delivery, this has led some medical experts to voice concerns that excess insulin in the digestive attract could trigger issues in local tissues.

Novo's diabetes research chief, Peter Kurtzhals, is a believer in the new approach, though.  He comments, "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.  If you can [modify the insulin molecule's breakdown time to several minutes], maybe it's sufficient time for absorption to take place.  Risk is still high for this type of project. But the chance of success has gone up quite dramatically in our own minds compared to what it was originally."

II. Israeli Startup Begins Phase II Clinical Trials of Diabetes Pill

But a small Israeli company is ahead of Novo for now.  Worth a mere $50M USD Oramed Pharmaceuticals Inc. (ORMP) is putting up a spirited bid to become the first successful insulin pill maker.

Founded in 2006, the Jerusalem-based company's product is based on research work done at the Hadassah-Hebrew University Medical Center.  Most of the work was done by Professor Miriam Kidron, who now serves as Oramed's chief scientist.  Her son, Nadav Kidron is the company's CEO.

Oramed's CEO shows off his company's star pill. [Image Source: Reuters]

He describes their journey, stating, "[My mother] is the chief scientist. I just went for the ride to do the business side.  My mother said it could be commercial but Hadassah won't be able to fund it.  I took the IP from Hadassah and started Oramed. Since then, we've been moving it forward.  If we give insulin earlier on, we're going to give the pancreas a rest.  We could reduce the complications, such as blindness and amputations.  There must be an oral insulin. This is going to be a huge market."

Skepticism from big pharma is not entirely unfounded Pfizer Inc. (PFE) poured a substantial amount of money and resources -- $775M USD according to one estimate -- into developing and testing nasal and oral sprays for insulin delivery.  The company tucked its tail and abandoned these efforts in 2007 after disappointing sales of its bulky "spray gun".

Pfizer's Exubera, while achieving clinical success, flopped on the market.

But Oramed's unique pill technology -- which includes bundling a protease inhibitor to prevent digestion of the pill -- could be just the kind of disruptive thinking needed to make this unlikely product a reality.  Mr. Kidron is convinced his company is sitting on what will become a $7B USD market in oral insulin.

IV. Medical Community Adopts Wait-and-See Attitude After Past Failures

Oramed has begun Phase II clinical trials with human patients -- a middle stage in a drug development cycle.  

Oramed clinical trial overview
[Image Source: Oramed]

It plans to complete these trials on its own, and assuming success look to partner up to complete the arduous task of completing expensive Phase III trials and convincing regulators in the U.S. and abroad to allow the drug onto the market.  If his company succeeds, Mr. Kidron told Reuters that Novo is even one potential partner/buyer.  He comments, "Novo is in a different league from anyone else out there.  I look up to them."

Other researchers -- both in academic and corporate settings -- are testing a variety of other deliver mechanisms, including sprays (like Pfizer's failed attempt) and skin patches.  But oral delivery is particularly appealing, as patients are used to taking drugs orally and there's certain logistical advantages.

Those factors have some doctors cautiously optimistic about the technology.  Dr. Jason Gaglia, a top researcher at Harvard Medical School's Joslin Diabetes Center, comments, "If you could give it in an oral pill that is just hitting the liver, it would be wonderful.  If people take this pill at dinner time, they're not going to have this excess glucose production overnight and it will be really good for getting those morning blood sugars down."


It may be years -- or even a decade -- before Oramed or Novo manage to bring the product to market, if they are succesful at all.  But an easier diabetes treatment is much needed as global diabetes are expected to rise from 285 million cases in 2010 to nearly 366 million cases by 2030 [source].  The driving factor is rising rates of Type 2 diabetes, which some research indicates can be caused by a so-called "Western diet" high in fat and simple sugar, as well as a lack of excercise.

An estimated 25.8 million Americans currently have diabetes, with as many as 7 million being unaware they have the disease.  Research has shown diabetes doubles the risk of death; it is directly the seventh leading cause of death in the U.S. and is indirectly tied to other leading causes of death including heart disease.

Sources: Oramed, Reuters

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