Understand the risks before you or a loved one inhales insulin

[h=1]MannKind wins approval for its inhaled insulin — and its stock drops?[/h]June 27, 2014, 4:30 PM ET

[h=3]By Russ Britt[/h]Regulatory approval for a new drug is usually a cause for celebration, but that wasn’t the case Friday for MannKind Corp.
The Los Angeles-area company won approval for its Afrezza, an inhaled delivery system for insulin, but investors apparently were concerned about warnings the U.S. Food and Drug Administration is requiring the company to put on the box of the rapid-acting drug.
MannKind Corp.MannKind Corp.’s Afrezza insulin inhaler
Shares of MannKind MNKD +10.30% plunged by as much as 20% at one point, before recovering some of those losses. Shares were down more than 5% in recent action to $10 apiece.
The FDA is making MannKind warn patients of possible bronchospasms for those with breathing conditions like asthma or COPD — chronic obstructive pulmonary disease. It also wants the company to remain in close contact with physicians to gauge how the drug is performing. The FDA will also require more trials for treating children and assessment of possible pulmonary cancer risks.
Afrezza is approved for glycemic control in adults with diabetes mellitus. It is designed to be used at the beginning of a meal or within 20 minutes after the start of a meal in order for it to work. The FDA stressed it is not a substitute for long-term insulin use.
“Today’s approval broadens the options available for delivering mealtime insulin in the overall management of patients with diabetes who require it to control blood sugar levels,” said Dr. Jean-Marc Guettier of the FDA’s drug evaluation center in a press release.

 

If it's not for long term use, what's the actual purpose and theoretical benefit? Did they mean it wasn't to replace long acting, or did they actually mean long term?

Not getting the advantage and seeing lots of scary disadvantages, ones that we may not know about for a long time. Not something that's going to enter into our regimen.

 

It's short acting insulin.

 

Same here. I wish I could remember on whose T1D blog I read about how the writer began using inhaled insulin shortly after diagnosis (if memory serves). Don't quote me on this, but I believe she used it for about 6 months with abysmal results before going on to use injected insulin. Granted, this is only one person's experience, but this anecdotal evidence along with the FDA's recommended warnings (or should I say what the FDA is making MannKind warn patients about) leads me to wonder how this drug received regulatory approval in the first place.

 

Yes, I understood that, but that disclaimer said "not for long term use". What does that mean, truly? Can you use it a week..a month...a year? What is long term use? And if you can't use it long term, why would you use it at all?

 

I'm very excited about this. I don't think we're going to see pediatric approval for years but I'm happy that this option is making progress. For T2 people that could benefit from insulin but are too afraid of shots, this gives them a way to improve their health. And, I am still hopeful that this will be an option for my kids some day, even if it's supplemental insulin to break highs, help recover more quickly from a failed site, or an easier way to split dosing for difficult meals.

 

I wonder if it's because of the fact that there aren't long-term studies yet? Is that an FDA standard for 'study participants have only been followed for one year'? It's like reading insulin approvals and seeing it's approved for kids over the age of 2...but it's still necessary for babies with diabetes...and it just means that they can't test babies. I'm just never sure when the FDA is involved...

 

I haven't read much about this inhaled insulin, but I was also questioning "not for long-term use". What does that mean - better for type 2s?

How do you adjust the dose? Kind of puzzling.

 

^^^^^ I am with StacyMM

being able to knock down a high in 20 minutes verses waiting an hour or two or three has to be a "good thing". I would use this tomorrow to solve that problem. Think of this as another tool in your toolbox.

The story behind the story though is that it gives you a sense of the massive investment it requires to bring a new technology to the diabetes market. It is tough to displace the status quo.

 

What they mean by "long-term use" is basically just saying, in regulatory-speak, don't use this for insulin dosing like you would a basal insulin that lasts throughout the day. This peaks within 15-20 minutes and is completely gone from the system in an hour.

This really isn't a story about the cost of getting to market... that is part of it, of course. But the main story is how MannKind just couldn't get it done before now -- they'd submitted Afrezza to the FDA twice before now, and regulators turned them down because of safety concerns and issues with the past device design itself. And now despite the concerns, the FDA wants to allow this to get into patients' hands (or lungs) and let them assess the risk and try for themselves with all the information in their hands.

Btw, on kids: MannKind expects to begin trial-testing for pediatric use sometime in 2015, and it could be 2017 before it's approved for use in kids with diabetes.

We'll have a comprehensive news post on this at DiabetesMine, first thing Monday morning.

 

Seriously? Wow. I have a strong gut feeling this will be one of those drugs we'll look at in hindsight and realize was a bad idea, with serious ramifications.

 

For those of you that were around when they started testing Lantus/Levemir/Humalog/Novolog/Apidra......did they study long term use of these insulins? Were those companies asked to track people for years prior to the insulin being approved or did they do the studies after? I am a newcomer and these insulins are just there, and I am thankful for all of them. But at some point they were new, and challenged the status quo of the time.

 

Yeah, I'll let others be the guinea pig on this one. And good luck getting volunteers for that pediatric trial. Eesh.

 

The FDA routinely approves drugs and devices that have side effects. That is just the nature of the business. It is up to the consumer and their medical professional to assess that risk before taking any medication or using any device. If there is a KNOWN carcinogenic or fatal risk for a drug or device, the FDA does not routinely just approve it and let people "assess the risk for themselves".

Don't get me wrong, I am not saying this is a great drug or a bad one. I personally would not give it to my child based on her other medical conditions and the issues it had in earlier trials.

 

Remember those members of this forum who flew to China to put their kids in that clinical trial with a drug that supposedly "reversed" diabetes? They have no idea about the long term risks. There are also clinical trials that enroll infants as young as 1 month old (for a different disease state). I would not be surprised if they got good enrollment for the pediatric trial of this drug. But I agree with you, I would not put Danielle in that trial.

 

More details here http://www.mannkindcorp.com/Collateral/Documents/English-US/Afrezza_MedicationGuide.pdf

note on page 7 "AFREZZA causes a decline in lung function over time as measured by FEV1."

 

You've brought up an excellent point and one I encounter frequently with my patients. A medication, device, or other form of medical treatment goes through a great deal of testing before the FDA approves it for use in the general population. (Some people are understandably frustrated by how long FDA approval takes when compared to how long it takes for something to be approved in, say, Europe.) No amount of rigorous testing before something is approved by the FDA can equal the "real-life" testing that occurs once something is used by the general public over a longer period of time. Herein lies the catch 22: how can anyone possibly know the long-terms risks to the general population until a treatment is used by the general population for an extended period of time? This is why I'm glad that I don't work for the FDA; doing so, IMO, would mean facing a lose-lose situation a great deal of the time. Let me explain. The FDA is criticized for waiting too long to approve treatments, thereby delaying their availability to those who (often desperately) need them. But when a particular treatment is found to cause problems (sometimes quite serious, irreversible, and/or fatal) after it has been in use for a longer period of time in the general population, the FDA is criticized for having ever approved said treatment in the first place. Exactly where is the middle ground? The answer to this question usually can only be answered in hindsight.

Don't get me wrong; I'm not saying these things in some misguided attempt to defend the FDA. As a consumer myself and a parent of a CWD, I'm in the same boat as everyone else. I want better treatment options for my CWD right now but I also want a guarantee that these treatment options are safe. No one wants to feel like a "guinea pig" or like they are placing themselves or their loved ones at risk by using a treatment that is new on the market. But the unavoidable truth is that there is no way to know the long-term risks until these risks are taken. And someone has to take them. No one in their right mind wants to be that someone.

All of that being said, I still feel very wary about using Afrezza, and at this point in time would not consider having my CWD use it.

 

I'm in the minority, too. I am happy it was approved. It's not for everyone and seems like it's a definite no for people with asthma (of which I personally am), but lots of medications aren't right if a patient has another condition.

I think with the lack of precise dosing, it wouldn't be a good choice for my child as a replacement for Humalog, but I would happily consider using it for those times when we completely f up a carb count or a site fails, etc. Seeing those double arrow ups and knowing that even though you are throwing insulin at the problem, things are going to get worse before they get better (and, in my daughter's case, require more and more insulin to fix) is very frustrating for me.

While I understand that a different delivery method would allow Humalog to do the same thing, until "they" come up with one - having this in my emergency supply kit sounds great to me; sort of like a mini dose of Glucagon - not something used every day, but very handy to have when the need arises.

 

I think the difference here, for me anyway, is that these drugs were simply faster, but the delivery method was the same, by injection. Delivery of insulin has been by injection since the invention of insulin, so that as a tried method is proven. Inhaled insulin is a completely novel and new method of delivery. I may end up being totally wrong and this may be the way of the future, but personally it seems counterintuitive to inhale any drug not meant for the lungs.

 

According the the package insert that Ellen posted it comes in single use cartridges of 4 or 8 units. So it would seem like you would have to adhere to a pretty strict carb count at all meals