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INSULIN INHALED

Injections are a part of life for most diabetics. Type 1 patients inject insulin into themselves multiple times per day, and as many as 40% of type 2 diabetics require at least one daily injection.

Thanks to the FDA’s approval of MannKind Corporation’s inhalable insulin therapy called Afrezza, needles just might be a thing of the past for some diabetics.

This announcement was a long time in the making. Since starting late-stage clinical studies almost eight years ago, the company has spent $1.8 billion dollars, conducted more than 60 clinical trials on 6,500 patients, and forged on after two FDA rejections. In this week’s newsletter, we will look at the potential benefits of inhalable insulin and examine how it is made.

FROM PLANTS TO PATIENTS

Protein therapeutics on the market today are delivered into the body invasively. They are injected into muscle, under the skin, or directly into the bloodstream. Why so harsh?

The digestive system, by nature, is terribly inhospitable place to be. If protein drugs were to be taken orally, the patient’s digestive track would break them down in the same way it digests proteins consumed in food. Proteins are very sensitive to their environment, which is why biomanufacturing is such a critically monitored phase of biologics development. The wrong formulation of a properly manufactured protein can kill its efficacy. How, then, is inhalable insulin possible?

Inhalable insulin traces its roots back to work done by plant physiologist Carl Leopold in the early 1990s. Leopold observed that seeds from certain plants such as soybeans with high protein content could become very dehydrated, yet be completely revived when they reabsorbed water. The functionality of the plant proteins had been preserved, even in the dried out state. Further analysis showed that survival ability depended on the sugar content of the seeds. Leopold used these observations as the basis for developing methods to preserve small proteins such as insulin in powder form. This work eventually led to the development of techniques used to develop inhalable insulin.

YOUR DELIVERY MAKES ALL THE DIFFERENCE

Inhalable insulin offers the obvious advantage of enabling diabetics to forego at least some of their needle sticks. In addition, the lungs offer tremendous potential for drug delivery. Tiny air sacs called alveoli greatly increase the internal surface area of lungs, which allow inhaled drugs abundant and direct access to arterial blood as opposed to just capillaries, enabling a potentially shorter time to reach its target.

Let’s remember that Afrezza is not the first inhalable insulin to be approved by the FDA. Back in 2006, Pfizer’s Exubra was the first, only to be withdrawn just a year later due to poor sales. What happened and why should MannKind hope for a better outcome?

First: the delivery device. Exubra’s device was large and unwieldy, making it difficult to carry and use discreetly in public. In contrast, MannKind’s delivery device is similar to a small asthma inhaler, making it highly portable.

Second: the potential medical benefits. When taken just before a meal, Afrezza appears to more closely mimic natural insulin spiking than Exubra or injectable insulins, with blood concentrations peeking around 14 minutes post-injection as opposed to 45 minutes. Clinical trials data also suggests that patients receiving Afrezza have fewer incidences of insulin-induced hypoglycemia.

Both of these points suggest that Afrezza has a better chance of success than the ill-fated Exubra.

COCKTAIL FODDER

MannKind’s founder, Alfred Mann, was also the inventor of the insulin pump.

ON THE HORIZON

If successful, MannKind’s proprietary Technosphere particle used to deliver insulin may soon be in demand for the delivery of other biologics. This is no small feat and even if inhalable insulin is successful, adapting this technology to other proteins is not a sure bet. At only 51 amino acids, insulin is among the smallest proteins around, and has a correspondingly simple structure. Larger, more complex proteins may not be as amenable to inhalation.

Even more revolutionary than inhalable insulin would be oral insulin. Toronto-based Generex has an oral formulation for insulin in Phase III trials. Their RapidMist inhaler delivers insulin particles that have been formulated to be easily absorbed through the mucous membranes of a patient’s mouth, thereby avoiding the digestive system.

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