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.”

It looks like Pfizer may have spent some big bucks on a ’survey,’ that — surprise, surprise — appears to have achieved results designed to get more doctors to write prescriptions for the drugmaker’s Exubera inhaled insulin.

The new survey titled “Reimbursement of Inhaled Insulins: Safety and Efficacy Concerns vs. Improved Patient Compliance,” was done by Physician & Payer Forum, a primary research service of Decision Resources, a pharmaceutical consultant and advisory company.

Guess who the company’s clients are? Drug companies like Pfizer!

Decision Resources boasts that its:

“client base is diverse - including large pharmaceutical companies, emerging biotechnology concerns, financial services, managed care organizations, and medical device manufacturers who turn to Decision Resources to help shape their strategy and master their chosen markets.” (emphasis added)

That means the company’s recent press release extolling praise for its new statistical look at Exubera inhaled insulin prescriptions could be viewed by some cynics as essentially an advertorial.

It paints a rosy sales outlook for Exubera, something that Pfizer certainly hasn’t felt since it bought exclusive worldwide rights from sanofi-aventis for $1.3 billion in 2006 to launch the drug. Critics have called the company’s acquisition of these rights little more than the purchase of a ‘billion-dollar bong.’

Saying that their survey shows “54 percent of primary care physicians and 41 percent of endocrinologist say they will increase the number of prescriptions they write for insulin generally,” they also allege that half of the seventeen (17) managed care pharmacy directors that they surveyed think that Exubera will help diabetic patients start using insulin earlier than they othewise might using injectable insulin.

How is asking just 17 managed care pharamcy directors about Exubera noteworthy? On the contrary, it’s such a miniscule number that it appears statistically insignificant.
Why is that significant? Because there have been widespread reports that physicians remain reluctant to presecribe Exubera for their newly diagnosed and existing diabetic patients.

For roughly a year, Pfizer’s Exubera sales were so poor that it wasn’t even reporting them to shareholders in its SEC filings. In February it was revealed that Exubera sales were $110M for 2006, the first year that the drug received FDA approval.

that offers access to high volume-prescribing physicians, specialists, and managed care organization representatives in the United States; analysis of events and survey participants’ responses to them; insight into prescribing patterns; and an examination of the implications of events and issues for the pharmaceutical market.

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.

According to a recent post on Cafe Pharma’s message boards, Pfizer, Inc. (NYSE:PFE) employees are being told that they must not “access web-based message boards as a lot of company information is being leaked out via public message boards.”

This new information was, not surprisingly, being shared on Cafe Pharma’s Pfizer public message board.
Regular readers of this blog may have remembered our reporting on several apparent disclosures (by seemingly anonymous members of Pfizer’s drug sales team) of alleged problems with Exubera quality control issues:

• July 25, 2006: One poster on Cafe Pharma’s message board discusses what sounds like potentially serious safety risks with the inhaled insulin:
  

  “[There are p]roblem[s] with high quality control failure in the inhaler and issues with 1 mg blisters.”

• February 5, 2006: Another (or perhaps the same?) apparent Pfizer sales rep. suggests that one reason for the diabetes drug’s delayed launch was that:
  

  [Pfizer] recall[ed] the inhalers because they aren’t working right.

If these open source revelations are indeed true, they could offer another possible explanation behind Pfizer’s delayed introduction of Exubera last summer, as was originally planned, to the fall of 2006.

At that time, Pfizer’s Karen Katin explained in a Nektar Therapeutics (NASDAQ:NKTR) press release that one reason for Exubera’s delayed launch was that the drug company’s inhaled insulin “education programs and manufacturing preparations are time-consuming.”

A review of these posts raises an important question: if there actually were quality quality control problems related to the manufacture of Exubera’s inhaled insulin and drug blister packets for diabetics, would they have been reported to the FDA?

And, if true, telling the company’s drug reps would have increased the likelihood that a member of Pfizer’s drug team could share this information publicly, as appears to have been done.

A new article in the New England Journal of Medicine poses a hyopthetical question for many physicians: when should they consider prescribing Pfizer’s FDA-approved Exubera inhaled insulin?

The NEJM article is written by Graham McMahon and Ronald Arky, two endocrinologists in the Endocrinology, Diabetes, and Hypertension department at Brigham and Women’s Hospital in Boston.

It appears to carry weight for doctors, particularly given that 1) it is in the NEJM, one of the most trusted medical journals in the world, and therefore relied upon by practitioners seeking advice for treating patients in their practices, and 2) because it provides a “case vignette that includes a therapeutic recommendation”, i.e., a scenario asking physicians to read the hypothetical, analyze clinical data and treatment guidelines, and evaluate the authors’ recommendations.

Here is the hypothetical that McMahon and Arky present:

A 52-year-old man with an 8-year history of type 2 diabetes mellitus visits his primary
care provider for advice. His glucometer readings at home have been high
despite treatment with a sulfonylurea, a thiazolidinedione, and metformin at maximal
doses. He has never smoked. His glycated hemoglobin value is 8.6% and his
fasting blood glucose concentration ranges between 170 and 220 mg per deciliter
(9.4 and 12.2 mmol per liter). His blood pressure, weight, and lipid profile are within
recommended target ranges. The patient and his physician discuss therapeutic
options and agree that insulin treatment should be initiated. The physician wonders
whether the patient might benefit from inhaled insulin and refers him to an
endocrinologist for evaluation.

They take a broad overview of the case that seems helpful for general practitioner’s who have Pfizer, Inc. (NYSE:PFE) drug sales reps trying to get them to write Exubera inhaled insulin prescriptions. They examine:

• The clinical problem of diabetes;
• Pathophysiology and Effect of insulin therapy and the use of oral agents;
• Clinical Evidence of Exubera’s effect (drawing on short-term studies where “more than 90% of the patients were white”);
• Clinical Use examining evaluation and drug approvals by the FDA and EU, Exubera drug formulary coverage by insurance companies, potential costs to patients, and a comparison to injectable insulin for Type 1 and Type 2 diabetics;
• Adverse effects and potential risks of Exubera usage;
• Areas of Uncertainty, including the development of antibodies to Exubera, and the fact that “the longer-term safety and efficacy of this form of [inhaled insulin] therapy have not yet been established.”

So what do they recommend? While this blog will not quote the entire article, and encourages readers to browse the complete NEJM article online, in your practice, or at the nearest hospital or university, we will tell you that the doctors conclude by saying: “we do not recommend the use of inhaled insulin in this patient.”

It’s worth a good read. As an added bonus, the authors also have a nifty video explaining Exubera inhaled insulin dosing and usage. Dr. McMahon explains, in a pleasant Irish accent, how the pulmonary drug delivery system works.