Friday, November 03, 2006

Inhalable Insulin May Be A 'Flop'

OK, I hate to say I told you so, but go back to my March 2006 post on Exubera and you'll see that I basically said I thought Exubera was overhyped, although I did so from the perspective of a patient with type 1 diabetes, whereas this report looks at it from the perspective of the type 2 diabetes market. Maybe I should be a pharmaceutical analyst on Wall Street? Its not rocket science here, its common sense.

Inhalable Insulin May Be A 'Flop'
October 31, 2006

Inhalable insulin is unlikely to achieve the blockbuster status the industry had hoped for, according to a new report.

According to the report from DataMonitor, the unmet need for these newly-formulated drugs is too low to fuel a multibillion-dollar market bad news for a number of manufacturers who have long pursued the development of newly-formulated insulin as a potential money-spinner.

The first inhalable version of insulin, Exubera, was expected by its maker, Pfizer, as well as many analysts, to be a revolution for the treatment of Type 2 diabetes and to be an important step for patients who are postponing insulin therapy to avoid injections.

However, "presented to great fanfare to physicians and shareholders all over the world as a sure-fire blockbuster in the making, in Datamonitor's opinion, Pfizer/Nektar's Exubera is unlikely to revolutionize insulin therapy as some might expect.

Pfizer launched Exubera in July for Type 2 diabetes in the US, and the figure being thrown around for the market potential of the therapy was as high as $1.5 bn ( 1.3 bn) a year.

Exubera, which is now also available in Germany, Ireland, and the UK, is expected to be followed, in 2010, by NovoNordisk/Aradigm's AERx-iDMS, Eli Lilly/Alkermes' AIR system and MannKind's Technosphere.

However, Datamonitor forecasts sales of Exubera to fall well short of previous estimates and stabilize at $207m by 2015, and predicts that once launched, Technosphere would generate $288m in revenue by that time, at the expense of its other three competitors.

According to Datamonitor, the companies have misjudged the urgency for the need of non-injectable insulin therapies. [Blogger note: Gee, you think?] Pfizer however, refused to comment on this, or the future sales predictions for the new drug.

According to the report, the core issue is that, although the new formulation of the drug would remove the need for injections, patients would still have to put up with the usual disadvantages of insulin therapy, including weight gain and the need to adhere to a restrictive meal-dependent administration routine. [Blogger note: Basically, this is what I said] Added to that, Poso cited the effectiveness of other types of diabetic treatments in the pipeline as a big challenge to universal uptake of inhalable insulins.

Indeed, a variety of non insulin-based new drugs are to be introduced for the treatment of Type 2 diabetes, including two dipeptidyl peptidase 4 (DPP-4) inhibitors to be launched next year, and two injectable Glucagon-like peptide 1 (GLP) agonists, expected to enter the market by 2010.

DDP-4 inhibitors, for example, are said to offer great tolerability and weight neutrality while the GLP-1 agonist class is claimed to substantially improve the efficacy of current non-insulin agents. And these drugs do not induce hyperglycemia, don't lead to gain and do not require complicated regimens for administration.

However, a Pfizer spokesperson says that Exubera does have an important role to play for patients for whom insulin was the best way of glycemic control. A Datamonitor analyst disagrees, stating "this concerns only a small patient subset with a marginal commercial potential."

The report also said that the introduction of inhalable insulins has added a set of further potential side effects to insulin - on top of hypoglycemia and weight gain: the unknown risk of carcinogenicity and long-term lung damage.

Specifically, there is concern about the potential effect of insulin, a growth factor, on the pulmonary vasculature, such as pulmonary hypotension and pulmonary edema.

The Pfizer spokesperson said that the findings from clinical trials showed that there is a low risk for potential effect on lung functions.

In addition, the report suggests that cost of therapy will also be a key issue for patients, and any inhalable that does not get reimbursement approval "will simply not sell."

Exubera, for example, has already been denied full reimbursement coverage by UK and German authorities.

More specifically it can be reimbursed for particular types of patients, including haemophiliacs and people with needle-phobia. But, the issue is that the restrictive reimbursement guidelines will put patients off.

"It is hard to get reimbursed for the general population and for these subsets of patients it involves lengthy negotiations between the physician and the health insurance," he said.

The number of people with Type 2 diabetes is expected to reach the 40m mark by 2012 and that is why pharma firms have seen a goldmine in alternatives to injectable insulin.

However, it's not all lost for them as, according to the report, even if they won't be the blockbusters they were hyped to be, the market will be large enough to accommodate the four inhalables in competition, Exubera, AIR, AERx and Technosphere.


Christine said...

"According to the report...patients would still have to put up with the usual disadvantages of insulin therapy including...the need to adhere to a restrictive meal-dependent administration routine."

Actually, I think a lot of the problem is that insulin in and of itself does not always mean a strict meal schedule, but inhaled insulin does. You can pump to cover carbs, you can shoot to cover carbs, you can't yet inhale to cover carbs because it's just not that precise yet.

BetterCell said...

The Market for Type 2 Diabetes(Insulin Resistant Disease) far outweighs the one for T1DM, which is why so many pharmaceuticals that are beneficial to IRD exists. I have never been a "big fan" of inhalable insulin for many reasons including the possibility of respiratory problems. However, I am very interested in the buccal mucosa delivery of insulin which Geberex has developed and is being used/tested in Ecuador. Since the insulin does not enter the Lungs, the risk of Respiratory damage is absent. Theoretically, I see no reason why this cannot be used in T1DM as well as IRD as stated by the manufacturer:
Generex's flagship product, Generex Oral-lyn™, is an oral insulin spray for the treatment of diabetes.

Generex Oral-lyn™ is a liquid formulation of regular human insulin that is delivered to the buccal mucosa by way of the RapidMist™ device,where absorption is limited to the mouth with no entry into the lungs. The rich vascularity of the buccal mucosa allows for much faster absorption of insulin and a shorter total duration of activity which makes Generex Oral-lyn™ an ideal prandial insulin as it can be conveniently administered immediately prior to meals with little prospect of hypoglycemia. Generex Oral-lyn™ can be used as a preventative pharmacologic agent by people with pre-diabetes to delay the onset of diabetes and by patients with type-2 diabetes to delay the onset of insulin dependence and the complications associated with diabetes.

Scott S said...

The important element to realize is that type 2 is caused by a RELATIVE insulin deficiency (as opposed to the ABSOLUTE insulin deficiency exhibited in type 1 diabetes). Regardless of the absolute number of users, insulin is usually part of the problem rather than the solution to the problem for most type 2 patients. There is already a wide body of scientific and medical evidence to substantiate that hyperinsulinemia (excessive insulin) seen in type 2 patients contributes towards accelerating microvascular and cardiovascular damage. Repackaging it may make insulin more appealing, but it does little to address the core problem of insulin resistance. It is for that reason that I doubt insulin will ever be the first treatment choice for endocrinologists treating patients with type 2 diabetes. As for those of us with type 1, I believe Pfizer made a HUGE mistake in abandoning the worldwide standard of measure (the unit) in favor of milligrams, making it tough if not impossible to translate dosages and requiring doctors and CDEs to prescribe different dosage ratios for Exubera vs. all other forms of insulin. I believe Novo Nordisk and Lilly will not make the same mistake when their products finally launch, which may prove to be the last nail in Exubera's coffin.

Christine said...

The difference between Novo and Lilly and Pfizzer is that those companies have been making insulin for years.

Scott S said...

You're right in that Lilly has been making and selling insulin since the discovery in 1922. Pfizer has no experience manufacturing insulin, and obviously, none merchandising it either!