MannKind Corp., the most aggressive company pushing ahead on bringing inhalable insulin to market post the Exubera debacle, took a hit last week when it was forced to announce that a critical marketing partnership didn’t pan out. Investors are now fighting over the company’s future.
As a PWD who watched the whole sordid Exubera story play out with a sad smirk on my face (we all knew the product was too clunky and hard to use – but darn, did they waste some money finding out!), I’m not sure whether I should be rooting for MannKind or not. I have mixed feelings on the whole notion of inhalable insulin, mainly because I worry about safety: we still have no clue what the long-term effects of insulin in the lungs will be. Who wants to be a guinea pig to find out? There’s also the problem of setting doses of the inhalable stuff, which per definition cannot be nearly as precise that with injections.
On the safety issue, BioWorld Today reports that MannKind does not expect Afresa to have to be reviewed by the FDA’s Endocrine and Metabolic Advisory Committee before it gains approval, hopefully early next year. The FDA is already “comfortable with insulin,” a company spokesperson says.
But a few paragraphs later, the story notes that “while Exubera was simply an inhaled version of injectable insulin, Afresa has very different pharmacokinetics and pharmacodynamics.” So why no scrutiny by the FDA endocrine experts?
According to MannKind: “The drug acts quickly, allowing better glucose control, yet it allows insulin levels to return to normal after digestion, preventing hypoglycemia and the need for diabetic patients to eat just to manage their insulin… (the company) has observed ‘absolutely clean histology’ with no indications of cancer risk in preclinical or clinical studies.” I hope they have loads of data on that last bit.
It also bothers me how central money is to the whole conversation around Afresa. Let’s be clear: Afresa is targeted at Type 2 patients who need basal (background) insulin only. “As happens so often in the diabetes space, investors look at the epidemic growth rate of (Type 2) diabetes and begin to see dollar signs,” writes David Kliff of Diabetic Investor. “In the real world injection fears are vastly over-rated and the reason more physicians do not prescribe insulin therapy has more to do with fears of hypoglycemia and need for greater patient education. But … it is much easier to buy into the needle fear story than to actually research the insulin market and understand its complex dynamics.”
As usual, a bold statement from Mr. Kliff. He also has this to say: “The fact remains that the time for inhaled insulin has come and gone. Even if Afresa is approved by the FDA, it will never amount to anything more than a niche product with sales in the millions not billions.” And that, he implies, makes inhalable insulin something of a “dead-end therapy” with no great potential to either help the masses or lead us closer to a cure.
All of this leaves me wondering whether I’d recommend Afresa to a diabetic friend or loved one — assuming it’s approved and comes to market any time 
soon. My 74-year-old mother is on metformin. If she needed a step up in her therapy, she most certainly would not want to “go on the needle.”
But would she really do well with loading plastic cartridges into a small yet complex inhaler device? Should I worry about her lungs? Or the fact that she might be facing lows, living alone? Or the premiums she’ll likely have to pony up (out of her fixed income) to get this “fancier” treatment? I just don’t know… I have mixed feelings. What would you do?
[Editor's note: I see that MannKind is working on some pretty revolutionary tiny inhaler device designs: the Dreamboat and Disposable models - appealing, but also maybe not ideal for seniors]
Amy, great post! If there are 30% of people who should go on insulin but won’t because of needle phobias, will the known benefits of better control outweigh the potential health risks of inhaled insulin? That’s the big question for me. If the answer’s yes, I think the product will be a success.
If the insulin is short-acting then how will it serve as a basal insulin for people with type 2 diabetes? Certainly there is little benefit for type 1 (either you go off the pump and then have to take 1-2 injections of long-acting insulin, or you stay on the pump, in which case, you would just bolus WITH YOUR PUMP). If the insulin action profile is truly miraculous, allowing “insulin levels to return to normal after digestion, preventing hypoglycemia and the need for diabetic patients to eat just to manage their insulin” (riiiiight…), then maybe it will be a success. Still, the lungs seem to be one of the few organs untouched by the effects of diabetes (as far as I know); why would I take ANY risk, especially when for me it would be less convenient? I agree, the FDA should give this very close scrutiny.
I personally feel that inhalable insulin is a product that was created by people who clearly aren’t a PWD. People often mistakenly think that the hard part about diabetes is the injections. As we all know the injections are the easy part its the rest that get challenging. I don’t really think that there is much of a market for this product. I could be wrong but most type I’s at least wouldn’t want to carry something of that size and inconvenience around.
Putting aside all the issues of potential lung problems and all the other issues, I can only imagine the taste would be kind of icky! I know that’s probably a small issue for most people, but not for me. I’m happy with my pump and my CGM.
Hi Amy-
Speaking of David Kliff, any recent commentary from him on when a final decision on Amlyin’s once a week Byetta is due from the FDA Thanks-
I was on one of the inhaled insulin trials a fews years ago (’02?) in Dallas. My biggest issue was the amount of control. You had 2 dose sizes to choose from. You either had to do a couple of the smaller ones or one of the larger ones, and nearly every time I used it, I would go low. It was a clunky machine to operate and there would always be some residue left over after you inhaled, so I don’t know how it could be as controlled as even being able to dial up half-units on the new pens.
The study I was in was focused on the ‘long-term’ effects but they were only testing lung capacity, before-during-and post use, rather than any MRI’s or lung/cancer effects. I think it ran about 6 months.
I would be concerned about offering this product to a senior. The lows seemed (at least to me) to hit rather quick and harsh. I can’t rate any of the newer delivery methods as it was a number of years ago that I was involved.
The alveoli were designed for the exchange of oxygen and carbon dioxide, not for insulin uptake. No thank you MannKind.
Thanks for Exubera,s image. I inform that the Insulin from outside the body is not an adequate treatment . Type 1 diabetics who would rather die than take their insulin injections
two points, all pointing to thanks, but no thanks (dosage control!)
1. a while ago i worked at a biotech, and one of the guys in business dev was ALL OVER inhalable insulin. he would drag me over for a coffee, his eyes all googley, and go on about how great it would be to no longer have to take shots. not a PWD, surprise! i tried to explain how that’s not the tricky part…
2. i’m on a team investigating how “high-risk medications” are handled in a pediatric hospital. of the five drug categories, insulin is one. i certainly would not recommend something as imprecise as an inhalable delivery, for kids or adults.
time for my basal dose! (heck, today’s short needles are a dream compared to what they had 26 years ago!)
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A pretty informative post overall, but why all the negative feedback. As a teenager with atypical diabetes, the kind where even my endocrinoligists is wary of putting in the type 1 or 2 category, inhalable insulin would be a godsend. I’ve given insulin injections to my grandmother for a while now, and when I was diagnosed gave them to myself. Not fun. I’m not taking insulin now, but the rigorous diet and excercise routine I need to manage my glucose levels is impossible for an active teen. I’m not sure if inhalable insulin is worth the trouble now, but I certainly hope research doesn’t end because it isn’t marketable.
I’d be interested to learn more about the faster-acting part of this. Could be to the diabetic community what the emergency antihistimine injection is to allergies.
I’m still learning from you, as I’m trying to reach my goals. I definitely enjoy reading everything that is written on your site.Keep the posts coming. I loved it!