Al Mann Q3, 2009 Earnings Call: "All preliminary studies have confirmed that we have successfully improved the efficacy of the device by over 30 percent, delivering the same amount of insulin to patients using only two thirds of the powder and with a single inhalation and lower air flow than with the first generation Med-Tone device."
Did 171 prove this is well? It looks doubtful, but we won't know until Medtone A1c data is released.
You cannot bridge the safety of the devices without first analyzing the efficacy of the devices. The differences in the amount of powder vs insulin each device delivers into the body and absorbed by the body is what the FDA wants to find out. A 30 U dose of Afrezza in Medtone delivers how much insulin into the body vs a 20 U dose of Afrezza in Dreamboat? This is the main question. Importantly, we're not just asking how much overall powder is delivered via the inhaler. That is obvious. We're asking how much insulin from that overall powder is getting delivered, absorbed and utilized by the body. For example, how much insulin is used by the body with a 20 U dose from the Dreamboat inhaler vs. how much insulin is used by the body with a 20 U dose from the Medtone inhaler.
There is a big difference in the total U of dose and how much insulin is used via that dose. This is important when analyzing safety because if one inhaler is catching more of the insulin/powder into the lungs before being utilized by the body, then they are not bio =. Think of it in terms of how the change of inhaler size affects the change of the insulin particle size. Regardless, the only way to measure how much insulin is being caught in the lungs, is to measure the efficacy (i.e. A1c's) of both inhalers vs. the RAA arm.
This was the entire purpose of 171 and the main reason for the last 2 CRL's. MNKD has yet to prove this. If they don't prove it this time, the FDA may reject the drug and not waste its time with another CRL.
Rapp, I would stop with the innuendo and the lies as all these have just been addressed by MNKD directly. Check their website. Whom would I trust in this case? Not a hard choice and it is not you...
Sentiment: Strong Buy
Dear Rapp appreciate your concerns however you are dead wrong and proving yourself as an idiot by stressing too much of non issue. If FDA follows your path it would mean every delivery mechanism that includes needles, calibration of syringe, etc (which could impact injected treatments have to do full trials on bio equivalency because FDA has zero tolerance in specifications.
FDA is looking to see if dream boat (gen 2) device is consistent and equivalent device as used in initial trials for delivering Afrezza which is exactly what Mannkind has done. Question is not about Afrezza but delivery of Afrezza through dreamboat so labeling needed for dreamboat could be approved. When you conduct such test on sample populations there is bound to be statistical variations as those would rely on different set of individuals and as these variations lie within framework of test and statistical end points agreed to by FDA.
Why is it so difficult to comprehend ?
Sentiment: Strong Buy
No, Lotus you are wrong. Only devices that were switched mid - stream, while one device contains all the safety data would fall into this category.
You're right about delivery of Afrezza. Is delivery of insulin through Dreamboat same as delivery of insulin through Medtone. The only way to measure how much insulin is passing through lungs and into the body is to measure the efficacy of both inhalers.
Is this really that difficult to understand? I hate to tell you, but it's about more than just FEV1.
Rapp has been proven to be a perpetual liar in many different posts, who twists and distorts information to try and prove his points. All people on this board, regardless of your position, are advised they should ignore his posts. Your positions should be based upon honest analysis and verifiable facts.
In addition, Rapp continually posts comments, and makes claims, as if he works for the FDA and knows what they are thinking. Many of his claims regarding how the FDA thinks, contradict actual articles and presentations prepared by individuals, that have or currently do work with the FDA.
Last, Rapp has made many comments that contradict the worldwide diabetic experts in the scientific and medical communities. Therefore, not only from an investment viewpoint is Rapp's lies and distortions bad, but even worse from a health viewpoint for any diabetic.
pfg, Is that why I have A1c's in the mid 5's and no signs of diabetic complications after 20 years of being a T1? I apologize if I refuse to let the disease kill me like many diabetics do. I've got 2 small children and I want to see them graduate college and start a family. If I wanted to have 7.0% A1c's like most lazy diabetics and suffer from blindness and kidney failure after a few more years, I could very easily do it. I could eat more ice cream and take less insulin. I could test my bg levels much less. I could be fat and lazy. I'd rather not. I'd rather be normal and healthy and have glucose levels like a non diabetic. It's not that hard. But you do need discipline. I treat my body the same way I invest. With a lot of hard work and discipline. By reading some of your posts, it's obvious you are foreign to those two concepts.
Biotech investing is all about the data. In fact, it's only about the data. Any time you spend looking at something other than data and numbers, is time spent wasted. If you try to mix any emotion with biotech investing, you're done. Game over. I wanted MNKD to succeed more than anybody. I wanted to be emotional about it. But numbers paint the picture. Nothing else.
Show me where I lied and I'll apologize. If you can't prove my "lies" just continue to keep calling me a liar and lose credibility each time you do it. Your choice.
I don't work for the FDA. It's called DD, something you may be afraid of doing. The info I post about is public information for all to see. In fact, it's almost all from Mannkind's own website and conference calls.
Rapp, do you have any idea what A1C reduction would be required to be "comparable"? Was this spelled out in the protocol? Or is it up to the FDA to decide? I would think "comparable" must be left in the eye of the beholder else MNKD would be setting themselves up for a pretty nasty law suit.
No, and I don't think it's important. "Comparable" is useless word that means nothing. It is a MNKD word, not a FDA word. Bioequivalence is a FDA word and should be a MNKD word, although that word is conspicuously absent from the PR's and conference call.
I do think both MNKD and the FDA know exactly what the bio = assays are and what is needed to achieve it. They are simply not telling us. For whatever reason.
I've stated before that they may be setting themselves up for a major lawsuit. I'm shocked that the longs aren't calling securities lawyers now with MNKD sitting on the bio = data while watching the stock already fall 37% form the 8/14 highs as a result.
And it will keep falling until they do release it and at least try to convince the markets that the two inhalers are bio =. The market knows bio = is a huge question and it will be relentless until MNKD proves it by releasing the Medtone A1c. A partner will not come close to MNKD if there is a question in their mind about bio =. They know the first two CRL's were b/c of bio =. Perhaps potential partners are being shown the Medtone A1c data, and not us. Unless it's proves the two inhalers are not bio = and then I don't know what MNKD is doing other than selling their shares which it seems a lot of them are doing anyways.
If longs think 5.50 is bad, wait until late October when there is no partner and Deerfield is shorting the hell out of their 40 million converted shares to drive the price under 2.60 by warrant expiration. No warrants = no $60 million = major dilution = stock under $1.00. Shorts won't even need a FDA rejection to drive the stock to sub $1.00. MNKD will do it for them by not releasing the data.
Source: Q1 2010 earnings conference call, 4/30/10.
Dr. Peter C. Richardson Corporate VP and Chief Scientific Officer: "We will present very clear data from our recently conducted bioequivalent study, which compared our second-generation device which we refer to as "Dreamboat" with a device used in our long-term clinical studies known as Medtone Model C. In this study, we have confirmed that we can achieve a pharmacokinetics profile, which is essentially indistinguishable between the two devices. But using only a single inhalation per dose, and that 30% reduction in the amount of insulin powder in the new cartridge compared with that which was necessary in the original device."
Do the results from 171 agree the former MNKD VP Dr. Richardson? The in vitro studies he referenced above were rejected by the FDA. They issued another CRL in response to them and said additional in vivo studies (i.e. trial 171) needs to be conducted to compare the bio = of two inhalers in a clinical setting.
The United States Food and Drug Administration (FDA) has defined bioequivalence as, "the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study." Source Wikipedia.
If you read former VP Richardson's comments, as well as Al's which I previously posted, as well as the FDA's definition of bio =, you may begin to realize how important Medtone A1c's are to proving bio =.
Yet investors are intentionally being kept in the dark as the stock price plunges . . .
u stated "the only way to measure how much insulin is being caught in the lungs, is to measure the efficacy (i.e. A1c's) of both inhalers vs. the RAA arm." If less insulin was delivered for Gen2, does it mean the gen2 is safer, like a non inferior trial for Tox.
jj, no, b/c u still have to bridge all the old data. There were a dozen or so safety trials within the past decade that need to be bridged. I think too much variability either way can disprove bio = and disallow MNKD from bridging the data.
If you take a look at all of the old safety studies and what they measured, you will see how they are about much more than just pulmonary issues. So in 171, less insulin isn't necessarily a good thing. MNKD needs to prove that the two inhalers were similar enough in dosing and efficacy so all of Medtone's safety data can be applied to the Dreamboat inhaler. Too much less or too much more in 171 is not a good thing. They need to be similar enough to satisfy the bio = assays and standards as agreed upon by MNKD and FDA. Period.