Inhalable insulin may be a 'flop', says report

According to the report, 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 II 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 revolutionise insulin therapy as some might expect,"​ said Datamonitor cardiovascular analyst Daniel Poso.

Pfizer launched Exubera in July for Type II 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 stabilise 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 Poso, the companies have misjudged the urgency for the need of non-injectable insulin therapies.

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.

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 II 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.

"These drugs do not induce hyperglycemia, don't lead to weight gain and do not require complicated regimens for administration,"​ Poso said.

However, a Pfizer spokesperson told In-PharmaTechnologist.com​ that Exubera does have an important role to play for patients for whom insulin was the best way of glycemic control.

Poso 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.

According to Poso, the issue is that the restrictive reimbursement guidelines might 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 II 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.

"These will co-exist because their diversity in terms of formulation and device-handling is sufficiently pronounced to cater for the wide spectrum of end users that is characterised by differences in medical status and personal preference; the market will split accordingly,"​ said Poso.