The US Food and Drug Administration (FDA) cleared Afrezza on June 27 in a decision that was in keeping with the recommendation issued by its Endrocinologic and Metabolic Drug Advisory Committee in April.
The approval – which covers use of Afrezza as a fast-acting insulin at meal times for those with Type 1 and Type 2 diabetes – prompted a surge in Mannkind’s share price and much speculation about the drug’s market performance .
The core of the Technosphere technology is the excipient fumaryl diketopiperazine (FDKP), which MannKind sources from an unnamed ‘major’ supplier with plants in Europe and North America.
In Afrezza, FDKP, water and the non-ionic surfactant polysorbate 80 are mixed and crystallised into uniform particles of 2 microns in diameter in combination with recombinant human insulin.
FDKP is highly soluble at pH 6.0 – the prevailing physiological pH in the lungs – meaning that when the Afrezza particles have reached their destination the excipient dissolves and allows the insulin to be rapidly absorbed.
According to the FDA review document released in April any “absorbed FDKP is not metabolized and is excreted intact, primarily in the urine. The FDKP in the small fraction of swallowed powder is excreted intact in the faeces."
The panel also concluded that: “FDKP does not facilitate drug absorption, does not compromise the integrity of airway epithelial tight junctions or damage cell membranes but functions solely as the particle matrix to carry the insulin to the lung.”
MannKind underlined its desire to license out the Technosphere in an annual report filed with the US Securities and Exchange Commission (SEC) in April.
"Afrezza utilizes our proprietary Technosphere formulation technology; however, this technology is not limited to insulin delivery...We are actively exploring opportunities to out-license our proprietary Technosphere formulation technology…Currently, we are actively working with several parties to assess the feasibility of formulating different active ingredients on Technosphere particles.”
Last month MannKind confirmed that it has already started ramping up production capacity at its facility in Danbury, Connecticut.