Researchers have been trying to find alternative ways of delivering insulin for decades, recognising that with 150 million diabetics around the world - and 300 million expected in the next 20 years - the demand for a non-injected formulation would be considerable. But progress has been slow, and Exubera itself has been delayed on its route to market.
In 2002, a clinical study revealed that Exubera provided equivalent blood glucose control to injectable insulin, but some patients receiving the drug experienced a decline in lung function that, while mild, raised fears about its long-term tolerability. There were also concerns that patients could develop antibodies to the product, which could compromise the efficacy of insulin therapy. Pfizer and Aventis have both had to conduct additional trials to explore these effects.
Exubera has yet to be filed in the US, which is the largest market for pharmaceuticals in the world. However, the European filing - and the EMEA's decision to go ahead with a review - reinforces the view that the data may now be robust enough to support approval.
Analysts said the project is still high risk, but that the rewards justify pressing ahead with the programme. Aventis has made conservative predictions for sales of the drug of around €1 billion, but some analysts believe it could do better, perhaps bringing in as much as €1.7 billion at peak.
The filing of Exubera in Europe helps Aventis reassert its independence as it fends off an unsolicited takeover approach from Sanofi-Synthelabo. It also gives the product a lead over another inhaled insulin product, Novo Nordisk's NN1998 (developed using delivery technology supplied by Aradigm), which is in Phase III testing.
Exubera is based on inhaler and formulation technologies developed by US company Nektar Therapeutics. The company's pulmonary particle technology creates spray-dried formulation of fine, aerodynamic drug particles that can disperse efficiently into the lungs, even when carrying relatively large molecules such as insulin.