For the most part, the concept of inhaled insulin has come ..... and gone. Pfizer's EXUBERA was, essentially, rejected by patients and physicians. Novo-Nordisk's AERx and Alkermes' AIR products never completed their clinical trials.
However, the MannKind Corporation has pushed forward with AFRESA.
Afresa consists of "Technosphere" particles, which are tiny lattices of crystals that form spontaneously from a liquid, but only under acid conditions (pH below 7). Powdered human recombinant insulin is attached to the lattices electrostatically, after which the particles are dried to a powder and loaded into a inhaler device. When the particles are inhaled into the lungs, they encounter a basic (alkali) environment (pH of 7.3 or 7.4), which causes them to dissolve instantly back into a liquid. The released insulin is then transported from the lung alveoli to adjacent capillaries, sending the insulin to the bloodstream very, very rapidly. The remaining liquid is simply voided from the body.
AFRESA reaches peak action in 12 to 14 minutes after the dose is delivered. This approximates natural physiology and helps shut down the liver from continuing to release glucose through the meal. Currently injected rapid-acting insulins (RAI) reach peak action in no less than 30 minutes or a bit longer. Moreover, AFRESA "gets in and gets out" more efficiently than injected RAI. Studies show as little as 18% of a RAI dose may be used during mealtime, as compared to 74% of the Technosphere insulin. Theoretically, this reduces the risk of hypoglycemia and / or relative hyperinsulinemia (elevated insulin level) in the few hours after a meal that can, on a chronic basis, help to promote a weight gaining trend.
The force behind Afresa, and MannKind, is Al Mann, a venerable billionaire who has already sunk a good portion of his fortune into Afresa. In 1979, after a series of inventions that led to very lucrative companies, Mann developed an insulin pump which was the genesis of yet another successful company: MiniMed (now part of Medtronic). In 1997, he learned of an inhaled insulin, created by a firm called Pharmaceutical Discovery, that peaked in only 12 to 14 minutes and had a bioavailability of up to three times that of the other inhaled insulins. Afresa was born, and Mann is determined to see it grow up. Given his track record, the odds are in his favor.
Phase 3 study results, recently presented at the European Association for the Study of Diabetes (EASD) annual meeting in Vienna, show AFRESA does suppress glucose release from the liver (endogenous glucose production) more efficiently than HUMALOG. Studies also show that Type 2 diabetics, using AFRESA as the only insulin in their treatment regimens, maintained adequate blood sugar control without any change in lung function.
The full Diabetes Health article ishereand the New York Times, with some negative opinions, covers ithere.
Our opinion? We participated in one of the Phase 3 trials, noted above, that did not go to completion (not EXUBERA). The inhaled insulin performed very well, for most patients -- some just couldn't get the hang of inhaling adequately. The device used in the trial was a bit cumbersome, but we had seen the second generation device that appeared to solve most of those problems. However, the study was terminated about halfway through the planned duration --- patients just didn't seem to prefer inhaling insulin. The availability of 31 gauge, or 32 gauge, injection devices (Pen needles or syringes) may be the most significant reason. In the end, it's just not a big deal to inject insulin anymore for most patients. Most will now tell you that fingersticks to monitor their blood sugars are much more annoying.
If AFRESA does come to market, however, it will be useful to have an alternative method of delivering insulin.Labels: Insulin, Insulin (Inhaled)
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However, the MannKind Corporation has pushed forward with AFRESA.
AFRESA reaches peak action in 12 to 14 minutes after the dose is delivered. This approximates natural physiology and helps shut down the liver from continuing to release glucose through the meal. Currently injected rapid-acting insulins (RAI) reach peak action in no less than 30 minutes or a bit longer. Moreover, AFRESA "gets in and gets out" more efficiently than injected RAI. Studies show as little as 18% of a RAI dose may be used during mealtime, as compared to 74% of the Technosphere insulin. Theoretically, this reduces the risk of hypoglycemia and / or relative hyperinsulinemia (elevated insulin level) in the few hours after a meal that can, on a chronic basis, help to promote a weight gaining trend.
Phase 3 study results, recently presented at the European Association for the Study of Diabetes (EASD) annual meeting in Vienna, show AFRESA does suppress glucose release from the liver (endogenous glucose production) more efficiently than HUMALOG. Studies also show that Type 2 diabetics, using AFRESA as the only insulin in their treatment regimens, maintained adequate blood sugar control without any change in lung function.
The full Diabetes Health article ishereand the New York Times, with some negative opinions, covers ithere.
Our opinion? We participated in one of the Phase 3 trials, noted above, that did not go to completion (not EXUBERA). The inhaled insulin performed very well, for most patients -- some just couldn't get the hang of inhaling adequately. The device used in the trial was a bit cumbersome, but we had seen the second generation device that appeared to solve most of those problems. However, the study was terminated about halfway through the planned duration --- patients just didn't seem to prefer inhaling insulin. The availability of 31 gauge, or 32 gauge, injection devices (Pen needles or syringes) may be the most significant reason. In the end, it's just not a big deal to inject insulin anymore for most patients. Most will now tell you that fingersticks to monitor their blood sugars are much more annoying.
If AFRESA does come to market, however, it will be useful to have an alternative method of delivering insulin.
Labels: Insulin, Insulin (Inhaled)