Pfizer and Sanofi-Aventis’ inhaled insulin drug Exubera yesterday scored a nod of approval from a US Food and Drug Administration advisory panel for use in both type 1 and type 2 diabetes, leaving both companies likely heaving a sigh of relief after a long-drawn-out road to the market. The efficacy of Exubera in type 1 diabetes was called into question in a US Food and Drug Administration briefing paper published earlier this week.

Although Pfizer’s so-called Study 107 investigating the intensive control of type 1 diabetes patients showed Exubera to be equivalent to subcutaneous insulin, “neither treatment group achieved a mean HbA1c [a measure of long-term blood glucose levels] of less than 7%,” considered to be the standard for type 1 diabetes therapy, said the agency. However, the FDA did concede that that “by the best-validated surrogate endpoint available (HbA1c), intensive control of type 1 diabetes appears possible for some patients with inhaled insulin.”

A second principal issue for the FDA committee was the postprandial glucose jumps seen with inhaled insulin compared to subcutaneous insulin in the type 1 study. Postprandial glucose increased by 15mg/mL in the Exubera group at 24 weeks while there was a 3mg/mL decrease in the subcutaneous insulin group. This “is undesirable due to an epidemiologic association of postprandial glucose levels with cardiovascular risk,” FDA said, adding: “Special attention may be needed to ensure control of postprandial glucose excursion, and to avoid fasting hypoglycemia.”

The company is proposing Exubera use in combination with a longer-acting insulin for type 1 diabetes, and for type 2 diabetes as monotherapy or in combination with other anti-diabetic therapies. On the upside for Pfizer and Sanofi-Aventis, however, the FDA’s clinical review of Exubera generally found the drug to be effective in control of hyperglycemia in all the type 2 diabetes indications the company is seeking, including monotherapy.

However, a study submitted by Pfizer comparing inhaled insulin with GlaxoSmithKline’s Avandia (rosiglitazone) in type 2 diabetes is not likely to be included in labeling, the agency indicated, because the trial length of just 12 weeks was considered inadequate even though the findings showed Exubera to be superior to Avandia in lowering HbA1c in type 2 patients.

Pfizer and Sanofi-Aventis filed for approval of Exubera back in March after an almost three-year delay caused by concerns the product may have an adverse effect on lung function [[03/03/05c]]. The companies were forced to conduct additional safety studies, and the FDA has said that declines in pulmonary function tests “were more common in inhaled insulin group patients than in comparator group patients,” with a mean decline of 118 mL in FEV1 compared to a 77 mL decrease for comparator agents. However, this decline in lung function was reversible, the agency added.

Exubera is being developed for both type 1 and type 2 diabetes and, if approved, would become the world's first-ever inhaled insulin product - potentially capturing a large slice of the multi-billion dollar market as patients seek an alternative to daily injections.

- Meanwhile, Pfizer’s worldwide head of development, Declan Doogan, has told Reuters in an interview that the company is set to launch a patient follow up programme to investigate further the compound’s safety: “This is a new departure and, of course, safety must be a major agenda item,” he noted. And on rumours Pfizer is planning to buy partner Sanofi-Aventis out of the Exubera deal, Doogan declined to comment, but did concede: “We are in discussions with Sanofi about how the compound will get managed into the future.”