Danish diabetes drugmaker Novo-Nordisk has opted to halt further development of its AERx inhaled insulin.

The pharmaceutical company’s new decision comes shortly after it Pfizer and Novo settled their patent litigation of Pfizer’s Exubera inhaled insulin.

Novo’s AERX inhaled insulin was in Phase III trials when the decision was made. The device previously that was previously shown being used in trials appeared huge (inset, left) — as big as a camcorder.

Bloomberg reports that the decision will result in Novo taking a $260 million (U.S.) charge.
Approximately 300 Novo-Nordisk employees are expected to lose their jobs at the company’s Hayward, Calif. research facility, according to the Contra Costa Times.
(Picture credit: Sacramento Bee)

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]

If a new post on Cafe Pharma is really from a Pfizer, Inc. (NYSE:PFE) drug detail rep, it could spell huge problems for the drugmaker’s Exubera sales.

A June 14, 2007 post suggests that one doctor that the diabetes drug rep spoke with had a patient on Exubera experiencing a signficant decrease in lung function:

“[She] los[t] over 100 points on her pulmonary function test Peak Flow. She has shortness of breath and can’t vacuum her house without resting now. She has been through CXR, PFTs, treadmill, VQ scan, and the doc can’t find anything other than her having been on Exubera to explain her newfound shortness of breath. The doc and patient are now struggling to find what else they can do to get this shortness of breath resolved — looking at steroids and other stuff now. Plus, he was bitching because Pfizer is sending him Adverse Event Reporting forms ad nauseum!” (emphasis added).

This anectdote of Exubera respiratory problems appears to confirm the fears that many physicians and diabetics have continued to express about Exubera: namely, that the inhaled insulin will not be a great way to treat diabetes if it creates pulmonary risks for patients using the diabetes medication.

In November, 2006, this blog reported on the results of a study by Tufts researcher Dr. Lisa Ceglia that raised important questions about the drug’s long-term safety. Dr. Ceglia’s primary reluctance to prescribe Exubera was that “for the time being, the most worrisome concern is the effect inhaled insulin may have on lung function.”

On February 1, 2007, this blog reported the results of an important study which concluded that the number of diabetics who would be ineligible candidates for Exubera should double in seven years. The study’s lead author, Prof. Timothy E. Davis of Australia, was also a member of another research team that first reported finding a link between Type 2 diabetes and reduced pulmonary function in 2004. Davis has been involved in the Fremantle Diabetes Study that tracks diabetic health over extended periods of time.

This blog previoulsy reported on allegations of quality control problems with Exubera that reportedly delayed brining the insulin inhaler to market. The reports included allegations that “[Pfizer] recall[ed] the inhalers because they aren’t working right,” and that there were “[p]roblem[s] with high quality control failure in the inhaler and issues with 1 mg blisters.”

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.

Exubera inhaled insulin drugmaker Pfizer, Inc. (NYSE:PFE) is expected to release the results of 2 scientific studies involving the diabetes drug at the American Diabetes Assocaition’s Scientific Sessions annual conference in Chicago this week.

The company and, researchers that it supports, are expected to present research findings involving ’stop-and-go’ Exubera usage over a 2-year period involving Type 1 and Type 2 diabetics. The findings concern pulmonary risks and safety issues (i.e., lung function) that remain an ongoing concern of many doctors and diabetics regarding the inhaled insulin.

It will be interesting to see how doctors view the results that Pfizer presents at the ADA sessions, particularly when Dr. John Buse, the orginzation’s president-elect, stated that he sees his job as “talk[ing] people out of (using)” Exubera.

Pfizer’s Exubera sales remain lackluster according to news reports and numerous online posts from anonymous drug sales reps from the company.

The ADA Scientific Sessions are supported, in part, by a grant from the embattled maker of Avandia, the diabetes drug from GlaxoSmithKline that the FDA ordered to carr a ‘black-box warning’ due to widely reported excessive risks of heart attacks and related safety and personal injury issues.