Thursday, March 09, 2006

Irrational Exubera-nce for Exubera


Pfizer Q&As About Exubera

As a vocal diabetes advocate, I have been surprised at how many people have asked me whether I am excited (or irrationally assumed that I would be excited) about Pfizer's recently FDA-approved inhalable insulin formulation known as Exubera. To listen to the media, it is a truly revolutionary development and people think that with inhalable insulin, our troubles are over. I wish it were so easy, but this reflects complete ignorance about what diabetes actually is. I usually disappoint people when I tell them that I am not even planning to try Exubera! I also communicate fairly regularly with a number of other type 1 (autoimmune-mediated) diabetes patients, and the general consensus is usually the same as mine, although the reasons do very somewhat.

Why? Well, first, it is important to understand that Exubera offers nothing fundamentally new in terms of diabetes treatment. It is basically regular synthetic "human" insulin (similar to the stuff discovered way back in 1922) which has been dressed-up and repackaged in a "new & improved" delivery method -- although the claim about being new or improved is debatable. According to the FDA documents, Exubera offers a more rapid time-activity profile than subcutaneously injected regular insulin because it is inhaled into the lungs and therefore reaches the bloodstream quicker, but that is no big deal because since the mid-1990's, insulin analogs which are genetically modified ever-so-slightly to overcome the significant delays caused by absorption of insulin through the skin have been widely adopted. Virtually everyone uses insulin analogs today, which is one reason why Eli Lilly & Company's Humalog (insulin lispro rDNA origin) became a $1 billion product and now outsells the combined sales of all of the company's other insulin formulations.

Many people just assume that living with injections is painful, and while I would prefer not to have to do this, after 30 years and constant refinements made to disposable syringes, injections hurt far less than blood glucose testing does. What is painful about using insulin is the complete imprecision of dosing. Knowing what dose of insulin to take is not even remotely scientific, and over the last 90 years or so, little has been done to refine the dosing process since the widespread adoption of carb(ohydrate) counting, assuming that protein, for example, has little if any impact, which is not true. My friend Deb Butterfield said it best when she said in a presentation given at the Japan Society for Pancreas and Islet Transplantation in Tokyo: "Knowing what dose of insulin to take was not then, and is not now, a precise science. It is not a simple analog of food, exercise, and insulin; rather it is a complex and seemingly random theory of chaos with a few discernable known variables. I was frustrated by my inability to achieve perfect control, and visits to the doctors that gave me no new strategies or tools, but simply repeated the mantra that diabetes could be controlled simply by being 'compliant' with a prescribed regimen of insulin, blood sugar tests, and diet."

The fact remains that there are dozens of variables which impact the balance, many of which patients with diabetes cannot even measure. Patients are instructed to observe "trends" in how their blood glucose levels respond to insulin dosages, but the reality is that diabetes educators are merely regurgitating variations on the same old theme, but offering nothing new in terms of managing the condition. It is for this reason, I believe that Exubera offers patients absolutely nothing other than avoiding a needle. It is akin to the introduction of packaging juice in Tetra-Pack containers (juice boxes) rather than packaging it in steel or aluminum cans. Sure, its a new package, but the contents contain exactly the same thing. One more important consideration is that fine-tuning of insulin doses before meals is really not possible to the same extent with the current delivery system of inhaled insulin as it is with an insulin pump, pen or syringe. Presently, the Exubera inhaler can dispense insulin only in increments of 3 or 9 units, which is terrible for those of us who are sensitive to even tiny changes in dosage. Clearly, if the patient needs a different dose, this would not be possible with the current inhaler.

There are also safety concerns about Exubera which I will not elaborate on here because they are less important issues to me personally because I have no interest in Exubera. But the fact is that patients using Exubera were statistically more likely to develop asthma than patients using injected insulin. As if patients with type 1 diabetes needed to add another chronic, incurable condition to reduce their lifespans further. As I wrote in my editorial entitled "Why Big Pharmaceutical Companies' Current Nanotech Efforts Should Fail", big pharma just doesn't get it, and after spending decades and billions of dollars on inhalable insulin, they deserve to be rewarded with very disappointing sales for this product. Its not the injections that are painful to live with, it is the imprecision, uncertainty and the all-too-real danger of giving the incorrect dose that leads to either hyper or hypo glycemia that is so painful to live with. Current methods of insulin administration simply cannot reproduce the healthy beta cell's ability to precisely control blood glucose levels. Insulin replacement (or supplementation) today is a dangerous balancing act with immediate as well as long-term consequences. By the Congressionally-appointed Diabetes Working Group's own admission, "Genetic engineering of the insulin molecule and new methods of delivery have improved insulin therapy, but in essence, the treatment for Type 1 diabetes has changed little since insulin was discovered." (see "Conquering Diabetes: A Strategic Plan for the 21st Century, Full Report from the Congressionally-appointed Diabetes Working Group, 1999", page 27 for details) In addition, Allen M. Spiegel, M.D. Director, National Institute of Diabetes and Digestive and Kidney Diseases admitted to Congress that "Insulin therapy, via daily injections or a pump, is a poor substitute for the body's exquisitely precise regulation of blood glucose by insulin-producing pancreatic beta cells." (see http://www.hhs.gov/asl/testify/t030624.html for his quote) Yet we continue to be fed this line of crap about "controlling" our blood glucose levels, a task that even many skilled medical professionals find difficult, and the pharmaceutical industry is motivated not by making our job easier, but by what they see as an easy sale to millions of people. Exubera does nothing to help here, because it is more of the same.

As a business person, I believe that Wall Street has foolishly assumed that Exubera will automatically become a blockbuster for Pfizer. Perhaps no Wall Street analysts have type 1 diabetes themselves or none of them have children with this condition, I don't really know, but frankly, I am not willing to invest in the assumption that Exubera will be a blockbuster drug for the company. Pfizer's stock jumped on the day the FDA approved Exubera, but the stock has since returned to previous levels. The February 15, 2006, BusinessWeek editorial, which featured an unusually honest viewpoint called "Irrational Exubera-nce for Pfizer?" written by Michael J. Russo and David Balekdjian said it best. According to their bios, the authors of that editorial are partners at The Bruckner Group, Inc. a consulting firm for pharmaceutical and biotechnology companies helping develop outcome-based health-care value and justify the prices of their products and services. In essence, they argue that Pfizer is unlikely to reap any huge benefits for Exubera because the company has priced Exubera too high.

As for the price premium for Exubera, it seems ridiculous to price a product that offers nothing new in terms of treatment at such a premium, and that will be Pfizer's downfall. The Chicago Tribune reports that Exubera is expected to carry a price tag of $4 a day in the U.S., which is 3 to 4 times the average daily cost of injected insulin for type 1 diabetics, assuming they are taking 3 to 4 injections, SG Cowen & Co. analyst Ian Sanderson said in a research note. The Tribune reports that Exubera's price could be a hurdle for subscribers of some health plans, at least according to some analysts. As a rule, health care plans provide incentives for their subscribers to choose cheaper remedies over newer, more expensive therapies. If managed-care plans decide to cover Exubera, it will likely be placed in an expensive tier of a health plan's formulary. That means patients will likely pay a monthly drug co-pays as high as $40 to $50 for Exubera vs. only $10 to $25 for injected insulin. Bruce Japsen, who wrote the article called "Inhaled insulin's cost may take breath away" for The Chicago Tribune suggested that Exubera is unlikely to generate the kind of sales Wall Street analysts initially assumed.

While the Juvenile Diabetes Research Foundation (JDRF) reportedly supports the development of therapeutics such as this that can improve the lives of people with diabetes, the organization also cautions that "inhaled insulin is not a cure nor will it replace the need for people with type 1 diabetes to take daily injections or to continue closely monitoring blood glucose levels." Because Exubera was designed to be taken mostly at mealtime to provide short-acting insulin, rather than to cover insulin needs throughout the day, JDRF also notes that Exubera will not replace the need for injections of long-acting (or "basal") insulin. JDRF also notes that "Exubera was not tested in children and has not been FDA approved for use in children [therefore] Exubera may be more appropriate for people with type 2 diabetes, who resist insulin injections and, as a result, do not maintain tight control." (see http://www.jdrf.org/index.cfm?page_id=104531). But a Piper Jaffray analyst noted that Amylin's Byetta holds multiple advantages over insulin for patients with type 2 diabetes, therefore their expectation was that Exubera was unlikely to gain much over that treatment. These are hardly ringing endorsements for Exubera, especially from the world's leading diabetes research organization.

So I am hardly alone in my less-than-enthusiastic opinion of Exubera. Perhaps Wall Street will come to its senses and realize that if this is the best Pfizer can do, its stock price should reflect that (the stock did enjoy a lift after the FDA approved Exubera, but it was a short-term gain). I have no intention to try Exubera, and no other patients with diabetes I know are planning to do so either, so I would dare suggest that the expectations for this product to become a blockbuster are unrealistic at best. They will have to invest in a form of insulin that never causes hypoglycemia before I rush out to buy it, and I believe that SmartCells, Inc. already has a long head start in that field!

3 comments:

Shannon said...

This was a great post.

In addition, my father works for a pharmaceutical company who was testing their own version of inhalable insulin a few years ago. They originally had Type 1 and Type 2 test groups. They later excluded the Type 1 group because it wasn't cost effective to market to those with Type 1.

I knew long ago Exubera was nothing to sneeze at. It's just one more thing you'd have to worry about amongst a long line of therapies that wouldn't be excluded from one's daily management.

Megan said...

Scott, I couldn't agree more with you.

Scott said...

Now to convince the millions of people who think our troubles are over when we can inhale insulin!!