Clinical study results demonstrate the efficacy of AFRESA inhalation powder

Oct 2 2009

AFRESA^® (insulin human [rDNA origin]) Inhalation Powder, a well-tolerated, ultra rapid acting insulin, showed no significant changes in pulmonary function and sustained glycemic control in adult patients with type 2 diabetes over four years of continuous treatment, according to data presented today at the 45^th Annual Meeting of the European Association for the Study of Diabetes. Results from the open-label, controlled study conducted with patients who had previously completed two three-month, randomized phase 2 clinical trials showed minimal mean change in forced expiratory volume in one second (FEV₁) over a four-year period for those treated with AFRESA. Additionally, patients using AFRESA therapy experienced glycemic control for at least four years.

“We are encouraged by this long-term study which demonstrates that over four years, AFRESA maintained glycemic control with changes in lung function comparable to that seen in diabetic patients treated with injectable and oral therapies,” said Peter Richardson, Corporate Vice President and Chief Scientific Officer, MannKind Corporation. “These findings add to the growing body of clinical evidence that AFRESA is a promising therapeutic option for this patient population.”

AFRESA is a novel, ultra rapid acting mealtime insulin therapy with an action profile that mimics meal-related early insulin release. Based on an extensive phase 2/3 clinical program, a New Drug Application (NDA) is currently under review by the U.S. Food and Drug Administration (FDA) requesting approval to market AFRESA Inhalation Powder and the AFRESA Inhaler for use in adult patients with type 1 and type 2 diabetes mellitus for the treatment of hyperglycemia. AFRESA is conveniently administered by oral inhalation.

Diabetes, which affects 23.6 million people in the U.S., or 8 percent of the population, is characterized by the body’s inability to properly regulate levels of blood glucose, or blood sugar. Insulin, a hormone produced by the pancreas, normally regulates the body’s glucose levels, but in people with diabetes insufficient levels of insulin are produced (type 1 diabetes) or the body fails to respond adequately to the insulin it produces (type 2 diabetes). Current mealtime insulin therapy regimens have a number of limitations, including the risk of severe hypoglycemia, the likelihood of weight gain, inadequate post-meal glucose control, the need for complex titration of insulin doses in connection with meals and the need for injections. Additionally, current therapies do not mimic the natural time-action profile of insulin normally seen in healthy individuals and present challenges in maintaining compliance.

Study Design and Key Findings

Findings were based on pulmonary function tests (PFTs) and A1C levels over a 4-year period in subjects with type 2 diabetes mellitus receiving AFRESA who had completed any of the two three-month, controlled, randomized, phase 2 clinical trials and continued open-label AFRESA as their exclusive prandial insulin regimen.

Based on the predefined endpoint, over 4 years, changes in lung functions were small and similar to the changes expected in adults with type 2 diabetes. Annualized change in forced expiratory volume in 1 second was -0.048±0.006 l/year, and in diffusing capacity of the lung for carbon monoxide was -0.332±0.085 ml/min/mm Hg after 4 years of continued treatment with AFRESA. Mean A1C levels were 7.97 percent at baseline and remained steady with a slight decline through month 48 (6.45 percent). Overall, hypoglycemia rates remained stable at 0.31 events/subject-month during the first 6 months and 0.42 events/subject-month after 3 years, as measured over the final 12 months of AFRESA therapy.