Dr Ahmed El Hakim, the Senior Manager of Pfizer’s (NYSE:PFE) Middle East Arab Group, recently defended the drug company’s lackluster worldwide Exubera inhaled insulin sales.

Downplaying the diabetes drug’s widely known poor worldwide launch, El Hakim explained to ArabianBusiness.com that “this is the price you pay as an innovator - the concept [of using inhaled insulin] has not yet been established, and while we are now establishing the concept of using this convenient therapy, sales have not been up to the expectations of many people.”

A study published in the World Health Organization’s journal, the Eastern Mediterranean Health Journal, concluded that diabetes was a growing problem in Saudi Arabia, citing the following factors:

• A high prevalence of obesity;
• A diet rich in carbohydrates (e.g., bread, dates, sugar, and potatoes);
• Lack of exercise; and
• Genetic factors

At the time the study was reported in 1998, it found that there was more than a 300% increase in Type 2 diabetics older than 30 in Central Saudi Arabia, from 6% in 1982 to more than 18.22% in 1998.  Pfizer’s El Hakim told a reporter that the country’s now approximately 25% of Saudis are diabetics.
That’s a huge potential market for the pharmaceutical company’s diabetes and cardiovascular drugs.

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.”

U.S. Department of Veterans Affairs (’V.A.’) has some fascinating conditions associated with the agency’s formulary list for approving health plan members’ use of Pfizer’s Exubera inhaled insulin.

Both of these conditions must be met:

• Doctor’s must have experience in managing diabetic patients on insulin
• Patient must have baseline spirometry and diffusing capacity for carbon monoxide (DLCO)

Also, the insured diabetic patient must either:

• Have severe persistent injection site problems such as lipohypertrophy, or
• Work in an environment that does not allow needles (e.g. prison guard)

In effect, it appears that the V.A.’s forumulary committee concluded that Exubera is generally not more effective than subcutaneous injectable insulin for either Type 1 or Type diabetics, and that working in a place where needles aren’t allowed would limit coverage of the diabetes drug to a relatively small class of insured patients.

You can read the V.A.’s full explanation of conditions associated with Exubera forumulary coverage by clicking here.

Pfizer, along with endocrinologists and researchers, presented the results of an Exubera safety study examining the effects of Exubera inhaled insulin on Type 1 diabetics for a little over 2 years. An abstract of the study can be seen below.

Here are a few important highlights and caveats regarding the study:

• It involved nearly 300 diabetics using Exubera inhaled insulin, and another group of almost 300 diabetics using injectable insulin.
• The study focused on Type 1 diabetics.
• Dr. Jay Skyler, one of the study’s authors, is a paid Pfizer consultant and occasional spokesman for Exubera. The ex-American Diabetes Association President appears in the drugmaker’s Exubera DTC advertising spots. Skyler is a consultant for Pfizer on Exubera and chaired the company’s Global Advisory Committee. He also gets paid by competing diabetes drugmakers to hawk their drugs.
• Skyler is a paid Scientific Advisor to a competing inhaled insulin developer, Mannkind Corp.

Pulmonary Safety Following Discontinuation and Readministration of Inhaled Human Insulin (Exubera[reg]) in Adults with Type 1 Diabetes

Authors:
PRISCILLA HOLLANDER, JAY SKYLER, LOIS JOVANOVIC, SOL KLIOZE, ALAN KRASNER, RICHARD RIESE, JOANN REIS, PAMELA SCHWARTZ, Dallas, TX, Miami, FL, Santa Barbara, CA, New London, CT

Results:

This interim analysis assessed pulmonary safety following discontinuation and readministration of Exubera[reg] (EXU; (insulin human [rDNA origin]) Inhalation Powder) therapy in adults with type 1 diabetes mellitus (T1DM).
T1DM patients (18-65 years) received EXU (n = 290) or subcutaneous insulin (SC) (n = 290) for up to 2 years in an ongoing, open-label study (comparative phase), followed by 6 months of SC insulin (follow-up phase) and a 6-month extension phase during which all patients received their original randomized therapy.

Small, nonprogressive treatment group differences in change from baseline forced expiratory volume in 1 second (FEV1) and carbon monoxide diffusing capacity (DLCO) occurred early during the comparative phase, and were not driven by outliers. These differences completely resolved upon discontinuation of EXU, and recurred to the same magnitude during the extension phase. Both treatment groups maintained glycemic control and hypoglycemic event rates were similar. Median insulin antibody levels increased in the EXU arm during the comparative phase (Month 24: 63.0 [micro]U/mL), decreased during the follow-up phase to near baseline levels (Month 6: 22.0 [micro]U/mL), and increased during the extension phase (Month 6: 42.0 [micro]U/mL); they remained stable on SC (Month 24: 4.4 [micro]U/mL; Follow-up Month 6: 4.4 [micro]U/mL; Extension Month 6: 3.6 [micro]U/mL).

In conclusion, FEV1 and DLCO changes observed during discontinuation and readministration of EXU therapy are consistent with a reversible, non-progressive and non-pathologic effect on lung function in adults with T1DM. EXU readministration is not associated with an augmented IAB response.[figure1][figure2]