Al Mann, CEO of MannKind Corp., is something of a legend in his own time. He not only founded MiniMed, acquired by Medtronic, but also four other successful medical companies. He's a billionaire, with his own Biomedical Engineering Institute at the University of Southern California (USC), so we can assume that he's not just championing the new inhalable insulin product Technosphere (brand name Afresa) as some kind of pipe dream or get-rich-quick scheme.
The guy knows his stuff, but a lot of folks remain convinced that the odds are against Afresa ever going very far. Today at DiabetesMine, a chat with Mr. Mann himself on the outlook for Afresa:
DM) Mr. Mann, let's jump right in. How do you expect Afresa to succeed in the aftermath of Exubera?
AM) Exubera was very inconvenient, it had absolutely no benefits clinically, and it was not as good as the other treatments on the market. Comparing Afresa to Exubera is like saying that Rezulin — a bad drug that failed — is the same as Actos — a good drug with good outcomes.
What we have is a different form of insulin (from Exubera). It's powder so we deliver it into the lungs. But that's an advantage because it's delivered in the arterial blood system instead of the capillary system. We're actually delivering insulin monomers (molecules). Nobody ever did that before.
It behaves much like normal pancreatic insulin does. Normal people don't get hypos, and people taking Afresa don't either, even if they dose and don't eat.
How is that possible?
Other insulins create an enormous period of hypoglycemia because there's an excess of insulin after you've digested your meal.
What happens is that if you eat a meal on regular insulins, Lantus and Humalog for example, 80% of the insulin remains in your body for up to 10-12 hours after your meal, which causes hypoglycemia.
With Afresa, there's no complex meal titration. You take a set amount, matched to your body mass and insulin resistance, determined with your doctor. You take that same amount every time you eat a meal. Then it's not important whether you eat 50 grams of carbs or 100 grams or even zero. Afresa essentially "turns off glucogenesis" so no glucose is secreted from the liver in reaction to food. Our trial studies are showing that patients are having no more glucose highs than normal non-diabetic people, and no more lows.
That sounds pretty magical. Does this work for Type 2s only, or is it an option for Type 1s now taking basal and bolus insulin?
Both could use it. Afresa is for prandial control — mealtime only - not basal doses. For about 70% of Type 2s, all you'll need is a regular set dose of Afresa. This will work for everyone except the "late-stage" Type 2s, who will need to take basal insulin as well.
It's different for Type 1's because there's a very big therapeutic window for them; their insulin needs are so differing. They can use Afresa to cover meals, yes, but they'll still have the issue that if they dose and don't eat anything, they'll get hypo, and if they eat a large meal, they'll need a larger dose.
The advantage for all patients is that they won't have to do carb counting or anything, because Afresa does not have to be so precisely matched to food intake.
So can you explain the details of dosing Afresa?
The cartridges come in sizes of 15, 30, 45 and 60 units. Again, for Type 2s, their doctor will help them select a regular dose based on their body mass and level of insulin resistance. If a person is already on insulin, you'll multiply the amount of rapid-acting insulin analog you're now taking by three, and that's where you'll start for your original dose. You need about three times as much Afresa as you do for an insulin injection.
Aren't most Type 2s currently treated with a basal insulin only, instead of mealtime dosing?
Yes, but that's the wrong way around. The correct therapy should be a good prandial insulin and not long-term insulin — Afresa in particular because it turns off glucose production and delivery from the liver. Our latest trials of 600 patients are showing even more significant benefits from the product than our original trials; the most recent trial appears to show that this should replace frontline treatment for all Type 2 patients.
That's a big statement for something so new. What about safety concerns? We hear that the FDA Endocrine Advisory Committee isn't even going to be scrutinizing this product...?
The FDA is already familiar with the kinetics of the product. We've done extensive safety studies, but not using Xrays like they did with Exubera. You can't detect lung cancer with Xrays. You have to do it in animals by sacrificing the animal at the end of the study, in order to examine every cell in the body and see if there's damage. That's how you find out if there's carcinogenicity.
We also did high-definition CT scans on the 600 patients in our study. That's the best you can do with people. We saw no change in their lungs, and some of them have been using the product for up to 5 years now.
How close are you to FDA approval then?
We've submitted all our data and recommendations, and our current review date is scheduled for January 16. That's when the committee will make their counter-proposal for the FDA label. The label says what you can use a drug for and what you can claim about it. We don't know what additional trials they might require to demonstrate superiority.
Getting back to usability, part of Exubera's problem was a form factor that simply wasn't liveable. Your tiny new Dreamboat inhaler looks amazing. Is this the delivery device we can expect at launch?
We hope so. Of course we did our clinical trials with the original MedTone inhaler - the little purple and white box you've seen in all the pictures. The new Dreamboat is pretty slick. We're hoping to get that approved by the time the FDA approves Afresa. We just have to do a short study with people using the two different inhalers, to show that the effect in the body is the same.
Are you worried that doctors will resist this new-fangled therapy, like they did with Exubera?
We actually did a survey of hundreds of endos and primary care physicians. Twenty-five percent said they would definitely recommend it for their patients.
Still, I ran into a doctor at a conference who thought it was nonsense to administer insulin with no complex meal titration. I tried to explain the science on which it was based... We'll have to give the doctors enough data so they understand and get comfortable with it. We believe Afresa's going to change diabetes therapy, but it's going to take a little education to do it.
Won't it be difficult to teach patients how to use?
Not at all. We have an instructional DVD and a test device that people can use to learn it in a few minutes right in the doctor's office. There's no big risk of hypoglycemia, so it's not so worrisome that people might make mistakes.
The bottom line is always costs. Will patients get insurance coverage for Afresa?
We're working with the reimbursement advisory panels to make sure we're within 5% of the current costs of Humalog and Novolog — so people will get essentially the same reimbursement they get now. We believe that we'll be covered by most mainstream health plans within six months of launch.
Don't forget this also saves a lot of money because you don't need nearly as many expensive test strips for fingersticks, by an order of magnitude. For Type 2s, maybe they'll just need a fasting test once a week. If you're Type 1, you will want to do a few more.
Afresa: Dreamboat or shipwreck? Only time will tell. Meanwhile, you can't help but admire Al Mann's unwavering commitment to bringing a workable inhalable insulin to market. Thank you, Sir.