Clearly shaken by the poor patient response to Exubera and the product's spectacular plummet from potential blockbuster to costly failure, Novo Nordisk will be dropping work on its AERx inhaled insulin system, currently in Phase III trials.

The decision will cost the Danish firm DKK1.3bn ($0.3bn) in charges involved in discontinuing clinical development and manufacturing activities related to the AERx system, and a significant number of the 350 employees at Novo's site in Hayward, California, are expected to be made redundant.

While there were no safety issues associated with the Novo product, the firm concluded that it was unlikely to offer significant clinical or convenience benefits over insulin injections with pen devices such as its own FlexPen product.

"After having analysed a vast amount of information, including very recent market research involving patients and doctors who used or prescribed the inhaled insulin product Exubera…we've come to the conclusion that a breakthrough in inhaled insulin takes more than AERx can offer," said Novo's chief science officer, Mads Krogsgaard Thomsen, during a conference call this morning.

The main gripes from patients using Exubera were that it was simply too complicated, impractical and inconvenient.

"[Patients] want very simple, very convenient devices for administering their insulin," said Novo CEO Lars Rebien Sørensen.

"This requires a whole new approach to inhalation of insulin."

While Novo has dropped the current AERx project, the diabetes therapeutics specialist does believe there is a still a place for inhaled insulin on the market.

Speaking to in-PharmaTechnologist.com back in October following Pfizer's withdrawal from the inhaled insulin market, Thomsen, perhaps exercising caution that Pfizer could have benefited from, commented that the company was "not willing to say that inhaled insulin will be a blockbuster product, but in our opinion we have to offer a portfolio of options for the patient."

In this context, although the current project has been dropped, Novo actually plans to step up R&D activities targeted at inhalation systems for long-acting analogues of GLP-1 and insulin.

These projects will take place at the firm's centres in Hillerød, Denmark (focusing on powder-based inhalation technologies), with a core team of 50 R&D scientists staying on at the Hayward, California, site to work on liquid-based inhalation technologies.

"We believe there is a rationale for pulmonary delivery systems," Thomsen said this morning.

"But our conclusion has become that the preference of physicians and Type II diabetes patients in the future will lie with the provision of longer-acting GLP-1 and insulin therapies in a pulmonary form that is at least on par with FlexPen in terms of simplicity and convenience."

So while Novo Nordisk's shares have taken a hit a result of the company's decision that AERx is not up to the job, there are a couple of players left at the table still clinging on to the promise of inhaled insulin.

The two most prominent contenders are Eli Lilly and MannKind; Lilly currently seen as the front runner with its AIR Insulin product due to hit the market next year.

"Lilly and our partner Alkermes continue to be committed to the development of our AIR inhaled insulin program," an Eli Lilly spokesperson told in-PharmaTechnologist.com.

"As to the recent decisions of other companies, we certainly work, as we always do, to understand the environment of the inhaled insulin class."

MannKind, on the other hand, has much more limited resources than Lilly and needs an external partner to get its Technosphere Insulin System off the ground.

Both companies still appear upbeat about their insulin products, and with the rest of the competition seemingly dropping like flies at least it leaves the market open for the taking.

Mopping up the bad publicity for inhaled insulin post-Exubera, however, could be significant irritation for the first to reach the market, without the additional sales, marketing and clinical challenges that introducing a completely new kind of therapy involves.

The question perhaps is whether last year's moves by the world's largest pharma company has sowed a seed of uncertainty large enough to cause a domino effect through the inhaled insulin competitors, or whether the smaller fry are brave enough to go it alone and stand by their innovations to succeed where deeper pockets failed.