A Worcester, Mass. newspaper, interviewed a senior endocrinologist at the Joslin Diabetes Center in Boston about the potential problems and pitfalls of oral insulin delivery.

Dr. Richard A. Jackson (inset, left) explained that “a chief concern in developing oral insulin products is ensuring dosage accuracy. Insulin levels are especially sensitive,” and experience has proven that injecting insulin subcutaneously using needles delivers accurate dosing.

“Small variances in the dosing and the speed of absorption is more important for insulin than other things. If absorption through the mouth varies by 15 percent, that’s a lot,” he said.

Guess what? This concern should apply to Pfizer’s Exubera inhaled insulin, as well as other potential oral insulin delivery products currently in the pipeline undergoing clinical trials.
These include Canadian-based Generex Biotechnology Corp.’s Oral-lyn, Mannkind’s Technosphere inhaled insulin, and the Alkermes / Eli Lilly & Co. AIR inhaled insulin — all of which are undergoing clinical trials.
Dr. Jackson emphasized that a critical issues is “whether [orally delivered insulin products] can achieve the accuracy and be consistent about how much is absorbed in the mouth.”

Respected money manger Bill Miller of Legg Mason (inset, left) shared his honest opinion about why he thinks Pfizer’s Exubera insulin inhaler isn’t doing so well: “it looks like a mini saxophone.”

That’s why Miller believes Mannkind Corporation’s (NASDQ:MNKD) Technosphere inhaled insulin could do much better if it passes Stage III clinical trials and then receives FDA approval:

“The MannKind product (inset, left) looks like a little asthma inhaler,” Miller said. “You pop it out, take a hit and put it back in your pocket.”

When this blog compared the size of Mannkind’s Technosphere with Pfizer’s bong-like Exubera inhaler six months ago, the difference was huge! Many believe that size really does matter when marketing pulmonary drug delivery devices.

At the American Diabetes Assocation’s Scientific Sessions starting this week, researchers will present the results of one study involving Technosphere inhaled insulin.

If Mannkind receives FDA approval for Technosphere, Pfizer would have competition for Exubera sales. Even though it currently ‘owns’ the inhaled insulin market beause it received FDA approval before anyone else, competition from another drugmaker could make things much more interesting for diabetics and their physicians.

Motley Fool finance web site contributor Brian Lawler lists Mannkind Corporation (NKTR:MNKD) founder Alfred Mann as someone whose medical device companies have been done very well by “keep[ing] you living well beyond when you might expire without” such technologies.

Lawler appears optomistic that, despite Exubera’s launch problems, Mannkind’s Technosphere inhaled insulin “[has] some potential advantages — like easier dosing — that could make it a much bigger hit than Exubera.”

This blog has noted, however, that perhaps the biggest thing that could convince diabetics to choose Mannkind’s inhaled insulin (if it gets FDA approval) over Pfizer’s is the small size of the drug delivery device compared to Exubera’s bong-like appearance.
That could mean a key question behind selling inhaled insulin — besides safety, efficacy, and affordability — is whether device size matters.

Update: Diabetic reporter Meredith Cummings has grown so frustrated with the erratic blood sugar levels that she experienced using Pfizer’s Exubera inhaled insulin, she’s going back to taking insulin shots.

In her latest report, Cummings says:

my blood sugars fluctuated wildly. A few days of this would make the most determined person physically, mentally and emotionally exhausted.

That’s not good news for Pfizer.

Just the other week, Cummings was complaining that her Exubera “inhaler was large and awkward.”

Yet what’s encouraging is that she still remains a diabetic who see’s her glass of Diet Coke half-full, not half-empty. Her decision to drop Exubera was made only after doing what Pfizer recommended: getting a spirometry (lung function) test to determine if she had any impediments to using the pulmonary drug delivery system; meeting with her endocrinologist; getting proper training on how to use the inhaler; and giving herself a chance to try using it.

Even though Exubera still didn’t work well for Cummings  (”I will gladly take insulin shots if it helps me to maintain that, as well as keeps me feeling good,” she says), that won’t trying another drugmaker’s inhaled insulin once it gets FDA approval.  “As soon as another company comes out with an inhaled insulin that is more fine-tuned, I know I will give it a try,” she says.

That could be good news for Alkermes, Inc. (NASDAQ:ALKS), Novo Nordisk (NYSE:NVO), and Eli Lilly & Co. (NYSE:LLY), and Mannkind Corporation (NASDAQ:MNKD).  Each of them are working on alternative inhaled insulin drug delivery systems.

In what appears to be the longest inhaled insulin trial to date, a Scottish hospital is currently recruiting Type 2 diabetics for a two-year study of inhaled insulin.

The Edinburgh Evening News reports that the study at the Edinburgh Royal Infirmary teaching hospital is seeking Type 2’s for the study.

Scotland Currently Rejected Inhaled Insulin For Nat’l Health Service Drug Formulary List

A Scottish drug forumlary committee listed inhaled insulin in an October-November 2006 report on new drugs that included inhaled insulin.  Evaluations by both the Scottish Medical Consortium (’SMC’) and the Lothian Recommendation and Forumarly Committee (from Scotland’s National Health Service) concluded, at that time, that inhaled insulin was not recommended for use by diabetics.

Only 8 Diabetics Currently Enrolled in the Drug Trial

Very few diabetics are currently enrolled in the trial.  At present there are only eight (8): four who are using inhaled insulin, and four taking subcutaneous insulin injections.
‘Needle Phobia’ Emphasized

It appears that a big push is being made by the head of the Scottish study to emphasize ‘needle phobia’ as a reason for enrolling in the study. The Infirmary’s Dr. Nicola Zammitt believes that “inhaled insulin could represent a major breakthrough in the treatment of diabetes for those with bad needle phobias.”

This has been a major emphasis by pharmaceutical companies like Pfizer when trying to get regulatory approval for inhaled insulin, and seems a likely component of any future Exubera Direct to Consumer (’DTC’) marketing and advertising campaigns.

Unclear Which Drugmaker is Conducted the Inhaled Insulin Trial

It is currently unclear exactly which pharmaceutical company is participating in the Scottish inhaled insulin trial.  It could be Pfizer, Inc.’s Exubera, Novo-Nordisk’s AERx inhaler, Mannkind’s Technosphere inhaled insulin, or AIR inhaled insulin which is being jointly developed by Alkermes & Eli Lilly & Co.