Inhalable insulin Afresa awaits US FDA approval

A fast-acting, inhalable form insulin Afresa to treat diabetes is currently on its way.

Afresa is the product of MannKind Corporation.  The U.S. Food and Drug Administration (FDA) has accepted and filed MannKind’s New Drug Application (NDA) for Afresa for the treatment of adults with type 1 or type 2 diabetes mellitus for the control of hyperglycemia.

Afresa has been studied in an extensive clinical programme  involving 44 completed studies and five ongoing studies at the time of submission.

The clinical trials included over 5,300 patients. More than 2,450 subjects with type 1 or type 2 diabetes were randomly assigned to treatment with Afresa in the pooled controlled Phase 2/3 clinical studies. In addition, the clinical pharmacology programme included more than 450 subjects exposed to AFRESA in single-dose studies. The extent of exposure meets the current guidance from the FDA regarding the development of therapies for the treatment of diabetes.

Afresa a drug-device combination product. It consists of Afresa inhalation powder pre-metered into single unit dose cartridges and the Afresa Inhaler as the delivery device for oral inhalation.

The large surface area of the lung provides unique access to the circulatory system. The pH-sensitive Afresa particles immediately dissolve upon contact with the lung surface, releasing insulin monomers that rapidly enter the bloodstream.Administered at the start of a meal, Afresa dissolves immediately upon inhalation and delivers insulin quickly to the blood stream. Afresa achieves peak insulin levels within 12-14 minutes of administration, effectively mimicking the release of meal-time insulin observed in healthy individuals, but which is absent or impaired in patients with diabetes.

“We are delighted to have reached this important milestone,” said Alfred Mann, chairman and chief executive officer of MannKind Corporation. “This NDA submission is the culmination of years of clinical research that has supported our long-held belief that Afresa will be a first-in-class ultra rapid-acting insulin with the potential to change the way diabetes is treated.”

Pfizer launched the first inhalable insulin product Exubera. Exubera was a powdered form of recombinant human insulin, delivered through an inhaler into the lungs where it is absorbed. Exubera was available from September 2006 to October 2007 in the United States as a new method of delivering insulin. However, in October 2007, Pfizer announced that it would be discontinuing the production and sale of Exubera,following concerns expressed by the Institute for Safe Medication Practices about a serious risk of dosing errors when prescribing Exubera. Related: Oral Recolulin insulin spray now in India

Exubera was also linked with lung cancer. Pfizer announced June 2008 that of the 4,740 patients who used Exubera in clinical trials, six have developed lung cancer,compared to only one of the 4,292 patients in the placebo group.

Several other companies are currently developing inhaled forms of the drug to reduce the need for daily injections among diabetics.

MannKind Corporation focuses on the discovery, development and commercialization of therapeutic products for diseases such as diabetes and cancer. Its diabetes pipeline includes Afresa, an ultra rapid-acting insulin, and MKC253, an inhaled formulation of human GLP-1. MannKind also has two cancer immunotherapeutic products in clinical development.