In a recent Motley Fool article (Nektar Full of Potential, Risk), Certified Financial Analyst Stepehn D. Simpson expresses skepticism about the success of Pfizer and Nektar’s Exubera inhaled insulin:

I’ve paid attention to the biotech and pharmaceutical space for a long time now, and I don’t think I’ve ever seen as much uncertainty about a drug as with Exubera
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In particular, I see more risk that Exubera sales might be disappointing — or even seem that way — than I do potential for to Exubera surprise folks.

No mention is made of any known or potential risks and safety issues associated with Exubera, and what impact, if any, that may have on the diabetes drug’s sales once it hits the market.

As a condition of approving Pfizer and Nektar’s new Exubera inhaled insulin, the FDA required a host of long-term drug safety studies.
These FDA-mandated clinical studies are intended to examine inhaled insulin safety risks for diabetics over an extended period of time.  Some of the issues the studies will examine include:

• Exubera safety for children with diabetes
• Decreases in lung function and capacity
• Autoimmune responses
• Exubera use by smokers
• Affect upon diabetics with pulmonary issues
• Hypoglycemia

According to the FDA’s information, some of these Exubera post-FDA approval studies have already begun.  Others inhaled insulin safety studies could commence this summer around the time that the inhaled insulin is anticipated to hit the market for diabetics.

• Required Pediatric Study Commitment

  1.  Deferred pediatric study under PREA for the treatment of patients with diabetes mellitus for the control of hyperglycemia in children and adolescents ages 6 through 17

  Protocol Submission Date: September 30, 2006
  Study Start Date: January 2, 2007
  Final Report Submission Date: December 31, 20011

• Postmarketing Study Commitment Protocols

  2.      5-year, large, simple trial in 5,000 diabetics with Type 1 or Type 2 diabetes, with 1:1 randomization to either Exubera or usual care. This trial will have two objectives. The first objective is to estimate the relative risk of development of clinically significant (>20%) decline in lung function as measured by pulmonary function tests. The second objective is to further investigate the potential clinical risk associated with increases in insulin antibody formation, with assessment of the relative risk of development of allergic and immune disorders.   (emphasis added)

  Protocol Submission Date: April 28, 2006
  Study Start Date: July 28, 2006
  Final Report Submission Date: December 31, 2015

  3.  Completion of Study 1022 in Type 1 diabetes to obtain data regarding changes in lung function over 5 continuous years and 7 cumulative years of Exubera exposure.  (emphasis added)

  Protocol Submission Date: N/A (Study in progress)
  Study Start Date: N/A (Study in progress)
  Final Report Submission Date: December 31, 2013

  4. Completion of Study 1029 in Type 2 diabetes to obtain data regarding changes in lung function over 5 continuous years and 7 cumulative years of Exubera exposure. (emphasis added)

  Protocol Submission Date: N/A (Study in progress)
  Study Start Date: N/A (Study in progress)
  Final Report Submission Date: December 31, 2013

• 5. Completion of Study 1028 in diabetics with mild to moderate asthma. This study will assess change in forced expiratory volume in one second (FEV1) and diffusion capacity for carbon monoxide (DLco), control of diabetes and underlying lung disease, and frequency and severity of exacerbations of underlying lung disease.  (emphasis added)

  Protocol Submission Date: N/A (Study in progress)
  Study Start Date: N/A (Study in progress)
  Final Report Submission Date: December 31, 2008

  6.    Completion of Study 1030, in diabetics with COPD. This study will assess change in forced expiratory volume in one second (FEV1) and diffusion capacity for carbon monoxide (DLco), control of diabetes and underlying lung disease, and frequency and severity of exacerbations of underlying lung disease. (emphasis added)

  Protocol Submission Date: N/A (Study in progress)
  Study Start Date: N/A (Study in progress)
  Final Report Submission Date: December 31, 2012

  7.   A study to determine the effectiveness of the Package Insert for prescribers, and of the Medication Guide for patients, in preventing the use of Exubera by smokers. This study will begin at first marketing of Exubera and include data for three years of use, with annual interim reports.   (emphasis added)

  Protocol Submission Date: April 28, 2006
  Study Start Date: First Marketing by August 31, 2006
  Interim Study Reports Annually in the Annual Report
  Final Report Submission Date: December 31, 2011

According to a Bloomberg News columnist, Germany is following the U.K.’s lead by concluding that Pfizer and Nektar’s new inhaled insulin, Exubera, is not a cost effective way to treat diabetics.

Amity Shlaes rationalizes in her article titled “Limiting Innovation,” that “ending injections means an improved quality of life” for diabetics.  She must not have diabetes herself, for if she did, she would realize that injections are probably the least of any diabetics real concerns in managing their chronic disease.  Taking an injection is like putting on glasses to see: you do it because you simply understand that it’s part of taking care of your condition.

She apparently ignores the more challenging aspects of diabetes management: regular blood sugar tests (5-10 times a day) to make time-sensitive changes and fine-tuning of one’s blood glucose control; regular activity and exercise; and, of course, eating right.

Shlaes seems more focused on encouraging reckless behavior amongst diabetics by suggesting that using Exubera inhaled insulin will let them satsify their sweet tooths:

“The issue [in Germany] is the millions of pensioners who amble into cafes during the afternoon sugar low. Among these German pensioners, as in the rest of Europe, diabetes is rampant. And since Germans, like the rest of us, are eating a lot of sweets these days, the incidence is set to mount.“

From a marketing perspective, an opinion piece like this one can only benefit drugmakers like Pfizer and Nektar by encouraging the use of FDA approved Exubera inhaled insulin to treat Type 1 and Type 2 diabetics who don’t appear to want to take care of themselves, and follow the advice of diabetes health professionals.

That appears to be the wrong message for diabetes treatment.  Encouraging diabetics to eat unhealthy foods and raise their blood sugars by using Exubera to treat this bad behavior is not a solution for treating diabetics.  Whether one uses inhaled insulin or insulin injections, proper self-care and diabetes management is likely more important for patients than their choice of medication.

A new article in the British science journal, Nature, asserts that “the efficacy and safety of inhaled insulin (Exubera) has been proven.”

That is a fascinating observation, given that the three authors also cite a number of safety issues and warnings that preclude some diabetics from using Pfizer’s new FDA and EU approved inhaled insulin.

They note a number of patient types for who Exubera is not appropriate, including smokers, people with “unstable or poorly controlled lung disease,” and people who stopped smoking less than six (6) months before attempting to use the inhaled insulin.  Although the authoris clearly state that Exubera was approved by the FDA and EU for adults, they fail to discuss why children with diabetes were specifically excluded from those diabetics who could use the insulin.

The author’s link in Footnote 8 to a European Union summary of potential Exubera safety risks does not work.

Exubera-Risks.com found, however, that an EU summary in English of Exubera’s drug approval highlights that “measures to minimise the risk associated with Exubera” appear to be largely promises by drug-maker Pfizer to conduct safety studies after the drug’s approval:

The company that makes that makes Exubera will carry out studies to further test its safety, particularly in patients who might have an increased risk of side effects, such as patients with asthma or chronic obstructive pulmonary disease. They will also look at the development of insulin antibodies (proteins that are produced in response to treatment with Exubera). The company will also monitor side effects, provide educational material, and improve the design of the blister packs so that it is easier to tell the difference between the 1 mg and 3 mg doses.

The authors of the Nature article are Prof. David R. Owens of the Diabetes Research Unit at the University of Wales College of Medicine in Cardiff, Joanne Grimley of the London global healthcare market intelligence company IMS Health, and Peter Kirkpatrick, and editor at Nature Reviews Drug Discovery.

On April 18, 2006, Britain’s National Institute for Health and Clinical Excellence (’NICE’) shared its preliminary recommendation that Pfizer’s new Exubera inhaled insulin:

should not be recommended for the diabetic (type 1 or type 2) population as a whole… [and] should not be recommended for patients whose bood glucose levels remained uncontrolled because of a very strong aversion to insulin injections.

This conclusion was based, in part, on NICE’s analysis that Exubera’s clinical effectiveness and cost effectiveness did not justify recommending a drug for British diabetics that would cost them roughly £500 more each year.  That’s nearly $1,000 U.S. dollars.

More importantly, NICE expressed a concern that, in order to justify any costs, more information was needed on Exubera’s effect on diabetics, recommending “treatment with inhaled insulin should be offered only as part of appropriately designed clinical trials.” That raises a question about what whether such trials would reveal more information about potential Exubera safety risks, and the Pfizer inhaled insulin’s effect on lung capacity.
The NICE recommendation led to a recent editorial in The Lancet, a respected British medical journal, titled “Patient Choice Stops at Inhaled Insulin.“  The editorial recommends, howoever, that even with Exubera’s unknown safety risks, physicians should be able to make decisions with their patients about whether or not “to make appropriate use of this new technology.”

The Lancet Acknowledges Exubera’s Potential Safety Risks

What is very significant about the U.K. journal’s editorial is that it expressed a genuine concern about the potential safety risks of Pfizer’s inhaled insulin:

For the group that might arguably benefit most from avoiding or minimising injections—children and adolescents—there is currently insufficient evidence on efficacy and safety. Long-term safety data are still lacking in terms of lung damage and effects on the development of insulin antibodies.

The U.K. debate over Exubera continues, with NICE requesting comments by May 10, 2006 on its preliminary recommendations.

Note: To read The Lancet editorial, a free sign-up to the journal is required online.