Certainly lots of Biotech companies fit that description as well. Fortunately Mannkind is not one of them given the current set of facts (you are entitled to your opinions but not to your facts). The landscape of Biotech-ville is littered with corpses of dead companies that were long on promise and short on (efficacious) products. The allure of bio-tech companies is simple. The promise of untold riches. I call this the low "P/D" syndrome. The D is for dreams, you just keep dreaming big about payoffs and any price (P) is justified & worth paying. Just like airline industry, the biotech industry as a whole has failed to deliver any returns. Though the biotech shareholders as a whole have suffered, the products that successful biotech companies brought have benefited patients and the general society enormously.
For every Amgen that succeeds, there are a thousand companies that took a one way ticket to oblivion. It pays to be vigilant. The motto should be Trust but verify. As I am long Mannkind, I follow "Bruce Berkowitz" (founder of Fairholme capital management) principle. Berkowitz principle is, you try to kill your idea. I wake up every day trying to punch hole in my theory. So far I've not yet found one. If you have one, please email me or post a comment.
Mannkind certainly makes some bold claims regarding Afrezza.Let's take a critical look.
Mannkind claims Afrezza (a.k.a. Technosphere Insulin, TI, Afresa) can
- Reduce postprandial glucose excursions to normal levels
- Virtually avoid causing hypoglycemia
- Require no complex meal titration
- Reduce the need for mealtime glucose measurements – likely just to infrequent fasting glucose measurements
- Cause no weight gain
- Eliminate prandial injections
I've three sources of information. One is from Mannkind's PR, next is the journal articles written by researchers (some of them are affiliated to Mannkind) and last is the Afrezza trial participants. I've had email conversations with one such participant named Pat. His feedback has been real useful to confirm the validity of several Mannkind's claims. He has written extensively about Afrezza in some diabetes forums. I've compiled the postings in this link. The participant is just another data point.
Claim 1: Reduce postprandial glucose excursions to normal levels
Validity: A good prandial insulin should be there when the body needs it and be out of the system when its no longer required. Lets explore how Afrezza stacks up.
a) A rapid suppression of endogenous glucose production can contribute to reduced PPG levels, and hence better control of PPG (indirectly).
b) On a head to head comparison with aspart, the PPG control was better in Afrezza
c) There has been numerous journal articles written on PPG excursions. Given the PK/PD profile, it is easy to conclude that this claim has merit.
Another measure of PPG is the AUCglucose (area under the curve). This result is from a phase 2 trial comparing Afrezza (TI -technosphere insulin) and Novolog. The table below is from Mannkind's PR.
What is interesting in the above table is, the total fluctuation is half of the industry standard RAA.
Claim 2: Virtually avoid causing hypoglycemia
Validity: Insulin and hypos go like peas and carrots. Hypos have been identified as one of the barriers of initiating insulin therapy.
a) From Mannkind's side, the best article on this is a poster titled "Reduced Incidence and Frequency of Hypoglycemia in an Integrated Analysis of Pooled Data from Clinical Trials of Subjects with Type 1 Diabetes Using Prandial Inhaled Technosphere® Insulin".
The pooled analysis shows a reduction in both mild to severe hypos compared to the RAA.
b) The best validation comes from Pat (the afrezza trial participant).
So one can conclude that though hypos are not eliminated, the frequency and severity of hypos are way less compared to the RAA.
Claim 3 & 4: No complex titration, infrequent fpg measurement.
If you talk to any diabetic, they will consider this as the most dubious of all claims. This is based on countless feedback from insulin users. If this is even partly true, then it'll be the greatest of all selling points. This claim challenges the conventional wisdom of internists, endocrinologists & patients. Even if this claim is true, it is going to take Mannkind considerable effort to change the mind-set.
Mannkind has put in lot of effort to back this claim. Let us see what Al Mann has to say on this in one of the recent quarterly call.
"I have long argued that AFRESA does not require complex meal titration. Certainly there is no need for carb counting and so forth. The basis of my view was derived from the dose escalation study with meal challenges in which better glucose control was achieved with ever greater doses of AFRESA, yet without any hypos.
This is what Pat had to say regarding the carb counting. The emphasis are mine. (Pat Godin | November 18th, 2009 at 2:56 pm)
I have also analyzed this issue a little bit. Why is carb-counting needed now? The simple reason is, in current treatment paradigm, you get hammered if you take a lot of insulin (resulting in hypos) and again if you do not take enough (hyperglycemia, higher A1C etc). The other reason is, if you know you made a mistake first, the correction becomes even more complicated. Any correction dose you take will get stacked on the existing dose (that is still in the body). The RAA's have a tail and you need to figure out accurately the correction dosage. (for folks who know math, think of superimposing one sinusoid curve with another and where the starting points are the same, it is a complex task.) Talk about adding insult to injury. In some ways, the current prandial insulin is unforgiving if correct dosage is not computed. So one has to count the carb, measure their fpg, use the sliding scale to compute the prandial insulin dose and then take the injection.
So what is the deal with Afrezza?
a) The Tmax of peak insulin is 12-14 minutes, so any corrective dosage acts real quick
b) The bolus doesn't crash (look at the PK profile of both TI and RAA, RAA comes down very fast), it is a gentle glide down
c) The tail of Afrezza is much shorter than RAA. Like a duracell battery ad, RAA goes on and on and on even when it is not needed.
d) To the extent Afrezza shuts off hepatic glucose, the body can use it later when it really needs it (reduce hypos etc)
It appears that Afrezza is much more forgiving to the dosage miscalculations.
Let us see what "Pat" says in a different post
Validity: A lot of evidence has been shown by Mannkind to validate this. Some studies have shown a weight loss and some have shown weight neutral.
Intuitively it is easy to understand. Due to the hypos or fear of hypos, the patients resort to frequent snacking. This snacking causes weight gain.
And last but not least, the claim 6 "Eliminate prandial injections" needs no validation.