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Post by biotec on Sept 4, 2014 15:42:35 GMT -5
I think the money is in Afrezza, Technosphere not so much. Even the cricket for pain and migrianes is along ways away. Also many pain meds out already. I bought MNKD for Afrezza. Any application going forward with technosphere will be many trials and years away from today maybe FDA approval, Also a hell of a lot of money needed.Vaccines for the old, young, and sick cant inhale. And as far as the flu shot, Its so easy, Every store not only drug stores but Walmart and grocery stores offer the walk in flu shot.And as far as the WHO goes the cheaper the better, Most of the Doctors and nurses are all volunteers. And using Technoshere for protection against diological attacks is just a crazy thought, Someone posted that. Anyway JMO.
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Post by jpg on Sept 4, 2014 16:32:02 GMT -5
JPG, Patients need to be educated re how to use Afrezza. I would imagine, one element is the inhalation technique...for maximum, consistent doses. Since vaccines are single doses, what do you think of the feasibility of a Technosphere application in terms of dosing efficacy? Could we ensure that the patient inhaled "enough?" Would we be able to tell when s/he didn't? If so, would a subsequent inhale be possible? --4B These questions and their answers are all part of what the trials would demonstrate. I for one see less of an issue with these roadblocks then many seem to think. There are a few easy validators for proper flow measurements and uses. The margin of safety for vaccines is a lot higher then for insulin. If we can 'do' insulin we can do many other things. JPG
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Post by dreamboatcruise on Sept 4, 2014 16:40:07 GMT -5
JPG, Patients need to be educated re how to use Afrezza. I would imagine, one element is the inhalation technique...for maximum, consistent doses. Since vaccines are single doses, what do you think of the feasibility of a Technosphere application in terms of dosing efficacy? Could we ensure that the patient inhaled "enough?" Would we be able to tell when s/he didn't? If so, would a subsequent inhale be possible? --4B These questions and their answers are all part of what the trials would demonstrate. I for one see less of an issue with these roadblocks then many seem to think. There are a few easy validators for proper flow measurements and uses. The margin of safety for vaccines is a lot higher then for insulin. If we can 'do' insulin we can do many other things. JPG It seems the devices (dreamboat and cricket) were developed such that the amount of drug delivered is fairly consistent across wide range of flow rate and volume. My interpretation of this is that they are designed such that a moderately week inhale sucks all of the powder out of the cartridge in less time than what would be a normal or perhaps even shorter than normal inhale time.
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Post by jpg on Sept 4, 2014 17:37:27 GMT -5
I don't think putting a flu vaccine into a Technosphere powder is a simple process. The FDA approval for something like this may take as long as Afrezza. This is something I'd wouldn't want to see spending 100 million plus on...not when an aerosolized vaccine would work just as well (except the inhaler is more complicated). And, Aerosolized vaccines (as far as I can tell) have been a complete failure. When I referred to considering injected flu vaccines when I'm 70..I'm saying when pigs fly. Unless there a serious health threat (I.e. potentially fatal) it's not going to happen. Now, when we are talking about disease prevention I'm all for it. But, let's say we have a Technosphere malaria vaccine. Are we going to distribute it in mass quantities in villages in Africa without medical supervision? Probably not...we are going to need to make sure people are educated on what it is, what it does, and potential side effects. Even if there are no side effects, we'd need to make sure people use the inhaler properly or just not thrown it in the trash. We'd also need to cross off villages, etc. that have been vaccinated. Are all people getting vaccinated? What about the infants? As you can see I'm not seeing a major advantage that would justify the cost. I think many are lumping in all current and future flu vaccines in a way which over simplifies flu vaccines. The VLP tech in itself is a huge paradigm shift without even adding in Technosphere. The 'classical' widely used flu vaccine is an old complicated to produce, cumbersome and immunologically not very good vaccine. I see the elegance of using Technosphere but do not have enough info to know why they need it. To stabilize the product, to avoid refrigeration, to gain access to the circulation quickly? The answer matters as to how necessary and central Technosphere is to the process. At this stage of the game it is all not so important but all this could or would influence IP/ revenue sharing negotiations I presume. I am not certain of what aerosolized vaccine you are referring to? The nasally administered live attenuated flu vaccine? If so it needs refrigeration big time and being live attenuated it would not do well with Technosphere obviously. What Technovax and Mannkind are describing as a new flu vaccine is to the old standard vaccine, a model T and Telsa type of equivalence. I certainly agree there would need to be a lot of money needed to test this. I would not look at this with the 'hundred of million' scale but more on the billion scale. I think a lot of people are looking at the vaccine space with limited understanding of the science and forming opinions based on a lot of emotional baggage. That is one of the reasons why I think this space is a poor investment. Until the public sees the value of vaccines I fear we will sadly stay with the pre genomic vaccine technology. Maybe if Ebola crosses the pond and panic ensues in rich countries then our governments will become motivated to move vaccines into the modern era. I see no other realistic scenario under which decision makers will move. As to your Malaria question the logistics of delivering (by health care workers) an effective malaria vaccine (if one ever were developed) to most places (not at war) are not that big a deal if the vaccine does not need refrigeration. As I posted previously I don't see the inhalation part as being that big a problem as many seem to think it is. On a different note and for those interested in the complexities of 'doing good' in Africa a recent Bloomberg/ BusinessWeek piece about Zimbabwe is an amazing read: www.businessweek.com/articles/2014-08-21/mugabes-bailout-och-ziff-investment-linked-to-zimbabwe-despotAs an MD who has spent a few years traveling/ working on off in Africa I would highly recommend anyone Interested in helping Africa read it. It reflects a big big part of what needs to change (from our perspective) to help things move forward in many places in Africa. Idealistic political message over...
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Post by jpg on Sept 4, 2014 17:47:52 GMT -5
These questions and their answers are all part of what the trials would demonstrate. I for one see less of an issue with these roadblocks then many seem to think. There are a few easy validators for proper flow measurements and uses. The margin of safety for vaccines is a lot higher then for insulin. If we can 'do' insulin we can do many other things. JPG It seems the devices (dreamboat and cricket) were developed such that the amount of drug delivered is fairly consistent across wide range of flow rate and volume. My interpretation of this is that they are designed such that a moderately week inhale sucks all of the powder out of the cartridge in less time than what would be a normal or perhaps even shorter than normal inhale time. Agreed. This is not that big a deal and easy to study. The name 'cricket' would even suggest that it makes a cricket noise when used properly maybe? Basically at 'x' flow rate the device delivers the powder and makes a noise like a cricket. If you don't hear the cricket sound you have to try again. Just to be clear: I am making this info up and have no specific info that this is what happens but it would be relatively easy to build this feature into a device of this type. JPG
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Post by seanismorris on Sept 4, 2014 19:58:41 GMT -5
FYI
From the CDC website:
The quadrivalent flu vaccine protects against two influenza A viruses and two influenza B viruses. The following quadrivalent flu vaccines are available:
A standard dose quadrivalent flu shot. A standard dose quadrivalent nasal spray, approved for people 2 through 49 years of age (recommended preferentially for healthy* children 2 to 8 years old when immediately available and there are no contraindications or precautions). ------
The take away, is there is already an alternative to injected flu shots. Also, a nasal spray may be a superior method than delivery to the lungs (avoiding issues with lung disease, COPD, asma, smokers, etc.).
Technosphere's big advantage is 'rapid acting' when you get a flu shot, it sounds like it takes 2 weeks to provide protection anyways...
---- Mannkind has limited resources to develope other Techosphere formulations. If a partner shows up to assume the costs (of vaccines) I have no problem with it. I just think it's money poorly spent. But, if it's not my money...
Quote: According to the National Vital Statistics System in the U.S., for example, annual flu deaths in 2010 amounted to just 500 per year -- fewer than deaths from ulcers (2,977), hernias (1,832) and pregnancy and childbirth (825), and a far cry from the big killers such as heart disease (597,689) and cancers (574,743). The story is similar in Canada, where unlikely killers likewise dwarf Statistics Canada's count of flu deaths.
Even that 500 figure for the U.S. could be too high, according to analyses in authoritative journals such as the American Journal of Public Health and the British Medical Journal. Only about 15-20 per cent of people who come down with flu-like symptoms have the influenza virus -- the other 80-85 per cent actually caught rhinovirus or other germs that are indistinguishable from the true flu without laboratory tests, which are rarely done. In 2001, a year in which death certificates listed 257 Americans as having died of flu, only 18 were positively identified as true flus. The other 239 were simply assumed to be flus and most likely had few true flus among them.
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Post by 4Balance on Sept 6, 2014 1:18:29 GMT -5
It seems the devices (dreamboat and cricket) were developed such that the amount of drug delivered is fairly consistent across wide range of flow rate and volume. My interpretation of this is that they are designed such that a moderately week inhale sucks all of the powder out of the cartridge in less time than what would be a normal or perhaps even shorter than normal inhale time. I came across this description of the "mechanical" factors associated with the design of Dreamboat and Cricket. It also describes the role of Bluhale. www.mannkindcorp.com/Collateral/Documents/English-US/Innovation%20In%20Drug%20Delivery%20by%20Inhalation.pdf
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Post by jpg on Sept 6, 2014 3:09:23 GMT -5
It seems the devices (dreamboat and cricket) were developed such that the amount of drug delivered is fairly consistent across wide range of flow rate and volume. My interpretation of this is that they are designed such that a moderately week inhale sucks all of the powder out of the cartridge in less time than what would be a normal or perhaps even shorter than normal inhale time. I came across this description of the "mechanical" factors associated with the design of Dreamboat and Cricket. It also describes the role of Bluhale. www.mannkindcorp.com/Collateral/Documents/English-US/Innovation%20In%20Drug%20Delivery%20by%20Inhalation.pdfHi 4balance, I kind of looked over (briefly) this stuff a while back but you now 'force' me to take another look (and a less brief one). Thank you. Sometimes we need a nudge! This article doesn't give a lot of clinical info. It mostly describes, in a very numerical but not clinical way, what would be deemed to be a good vs failed breath. After reading this my impression stays the same. People who can't comprehend what is being asked of them (basically making a seal with their lips around the mouth piece and breathing in 'almost quickly' to quickly) will not be able to use this. Everyone else pretty much would be able to do this. From what I understand the specs are for Gen 2 only and not the Cricket. The minimal Peak Inspiratory Pressure (PIP) pressure differential that needs to be generated for 2 seconds (PIP 0-2) needs to be at least 2 kPa. This doesn't mean a lot without knowing resistance and therefor flow values. Figure 6 shows a pressure/ flow 'translation' on a device between kPa and peak flow rates. There is no reason to believe the Cricket would be much different then these Gen2 numbers. The graph shows 2 kPA is about 22 l/ min. If you can't generate that then you have problems. Big problems... Using a Mannkind product is probably not your priority. The values are for 2 seconds though so averages and therefor 22 l/ min is not a peak flow (if you can't do 22 l/ min peak you should be on a ventilator in the ICU). Still 22 l/ min for 2 seconds is not the exclusive territory of olympians... Figure 7 shows that from very little flow (2 kPa) to 6 kPa things go well. 6 kPa equals a more respectable 70-75 l/min which is still manageable by cooperative non moribund patients but takes some effort to do it for 2 seconds. Young people could easily go significantly over this and 'over inhale'. They could theoretically get less medication deep into their lungs but the paper doesn't look at someone trying hard to do it wrong by overinhaling. In my experience kids tend to do that a bit but they have small lung volumes so it wouldn't matter as much I presume. Even less the focus of this paper obviously. The text and figure 9 and 10 seem to imply that Area Under the Curve ( pressure time curve) AUC for the first second only matters for effectiveness. Basically stuff happens in the first second so no need for long unending inhalations. As a side note the Cricket is described as having a Purple button but on the picture it is blue? I guess they have been through a few generations of those also... After looking at how the BlueHale works I would again speculate that the Cricket is named after the sound it probably makes when working properly? JPG
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Post by jpg on Sept 6, 2014 4:12:07 GMT -5
FYI From the CDC website: The quadrivalent flu vaccine protects against two influenza A viruses and two influenza B viruses. The following quadrivalent flu vaccines are available: A standard dose quadrivalent flu shot. A standard dose quadrivalent nasal spray, approved for people 2 through 49 years of age (recommended preferentially for healthy* children 2 to 8 years old when immediately available and there are no contraindications or precautions). ------ The take away, is there is already an alternative to injected flu shots. Also, a nasal spray may be a superior method than delivery to the lungs (avoiding issues with lung disease, COPD, asma, smokers, etc.). Technosphere's big advantage is 'rapid acting' when you get a flu shot, it sounds like it takes 2 weeks to provide protection anyways... ---- Mannkind has limited resources to develope other Techosphere formulations. If a partner shows up to assume the costs (of vaccines) I have no problem with it. I just think it's money poorly spent. But, if it's not my money... Quote: According to the National Vital Statistics System in the U.S., for example, annual flu deaths in 2010 amounted to just 500 per year -- fewer than deaths from ulcers (2,977), hernias (1,832) and pregnancy and childbirth (825), and a far cry from the big killers such as heart disease (597,689) and cancers (574,743). The story is similar in Canada, where unlikely killers likewise dwarf Statistics Canada's count of flu deaths. Even that 500 figure for the U.S. could be too high, according to analyses in authoritative journals such as the American Journal of Public Health and the British Medical Journal. Only about 15-20 per cent of people who come down with flu-like symptoms have the influenza virus -- the other 80-85 per cent actually caught rhinovirus or other germs that are indistinguishable from the true flu without laboratory tests, which are rarely done. In 2001, a year in which death certificates listed 257 Americans as having died of flu, only 18 were positively identified as true flus. The other 239 were simply assumed to be flus and most likely had few true flus among them. I agree with some of what you are saying and will add that: I agree with you that I do not think MKND should take this on alone. It would be folly. At the same time there is not one piece of evidence that even hints that MNKD is considering doing this. Mann knows what a billion costs... You may be cherry picking your data about flu deaths. Flu did kill more people then WW1 did and in a shorter time frame. There is little reason to believe another pandemic will not happen again. There have been other 'small flu pandemics' more recently which have killed a lot of people. If and when another major pandemic happens the current way of preparing vaccines will only protect a few % of the worlds population. You and I happen to be part of a rich western population with governments that still plan for those 'little things' and we will most likely be much more protected then billions of less privileged who will not have our luck. VLP could easily deliver more then 10 times as many doses much much more quickly and with probably much better and quicker immune responses then currently available flu vaccines can. About 1 billion or so would need to be spent to see if this hypothesis is true... Technosphere in this context is not being used for the reasons you seem to think. You are thinking of the advantages of Technosphere for insulin and erroneously extrapolating your understanding of the insulin paradigms to other applications. My previous post stated: I see the elegance of using Technosphere but do not have enough info to know why they need it. To stabilize the product, to avoid refrigeration, to gain access to the circulation quickly? My gain access to the circulation quickly was used in an immunological context and could be confusing I guess. The big deals of Technoshere for this application are probably to stabilize the product and avoid refrigeration but we don't have enough info to know. An antigen delivered to the blood does tend to create a rather strong and quick reaction so this could be part of the advantages? In my work I am forced to get a vaccine yearly by ill-informed dogmatic politically motivated public health officials or wear the useless 'mask of shame' for months and months. I go with FluMist (against the wishes of the same ill informed public health officials where I live) which is the nasally inhaled live attenuated vaccine I h alluded to and which the CDC reference you provided describes briefly. Flutist is by no means a perfect vaccine. It is live attenuated, needs refrigeration and is rather cumbersome to use. It is better then the old stuff but incrementally better. VLP and Texhnosphere is potentially exponentially better. Do you have a billion? JPG
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Post by 4Balance on Sept 6, 2014 13:22:43 GMT -5
Hi 4balance, I kind of looked over (briefly) this stuff a while back but you now 'force' me to take another look (and a less brief one). Thank you. Sometimes we need a nudge! This article doesn't give a lot of clinical info. It mostly describes, in a very numerical but not clinical way, what would be deemed to be a good vs failed breath. After reading this my impression stays the same. People who can't comprehend what is being asked of them (basically making a seal with their lips around the mouth piece and breathing in 'almost quickly' to quickly) will not be able to use this. Everyone else pretty much would be able to do this.
From what I understand the specs are for Gen 2 only and not the Cricket.<snip> If you can't generate that then you have problems. Big problems... Using a Mannkind product is probably not your priority. The values are for 2 seconds though so averages and therefor 22 l/ min is not a peak flow (if you can't do 22 l/ min peak you should be on a ventilator in the ICU). Still 22 l/ min for 2 seconds is not the exclusive territory of olympians... Figure 7 shows that from very little flow (2 kPa) to 6 kPa things go well. 6 kPa equals a more respectable 70-75 l/min which is still manageable by cooperative non moribund patients but takes some effort to do it for 2 seconds. Young people could easily go significantly over this and 'over inhale'. They could theoretically get less medication deep into their lungs but the paper doesn't look at someone trying hard to do it wrong by overinhaling. In my experience kids tend to do that a bit but they have small lung volumes so it wouldn't matter as much I presume. Even less the focus of this paper obviously. <snip> As a side note the Cricket is described as having a Purple button but on the picture it is blue? I guess they have been through a few generations of those also... After looking at how the BlueHale works I would again speculate that the Cricket is named after the sound it probably makes when working properly?
JPG JPG, I had the same sense that Gen2 (Dreamboat) had been designed for success in an adequately broad range of inhalation scenarios: "The end result was a high resistance, breath-powered delivery device system with robust performance across a large spectrum of patient inhalation efforts." I'm guessing that Cricket was designed with same parameters. (Perhaps "Gen2" is broad enough to cover both single-use and reusable devices.) That audible feedback with "success" would seem like a great design feature--especially if it were to be used to treat NONchronic situations...where patients did not have the opportunity to "practice" getting it right. But if you're tying that assumption to the sounds Bluhale is picking up, it could simply be air flow sounds. I think Bluhale was used with Dreamboat..which probably does not have audible feedback. There's a 2010 copyright date on the article, but perhaps certain design features were in flux...like the color of the button. It still is not clear to me that both Cricket and Dreamboat were approved by the FDA in April. But if both have been around since 2010, one would hope both were covered. Interesting observation re kids. One of the next studies should be to evaluate Afrezza's efficacy in the under 18 population...I don't recall the minimum age. We were expecting the need for the availability of smaller doses...but you might also be building the case for the use of one device over the other. In reality, though, the ability of a child to inhale correctly, consistently might be, far and away, the most important factor (setting dose aside) in determining minimum age. --4B
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Post by dreamboatcruise on Sept 6, 2014 13:56:24 GMT -5
4balance... that article has some details such as the range of molecular weights suitable for drugs that I never seem to have at hand when I want to cite them... thanks. Not withstanding the scandalous conflating of blue and purple that is... have they no scientific ethics? or proper photoshop calibration files? I hate to think the heyday the shorts will have when Adam F. uncovers this fraud in a lengthy article.
The whole platform really is a bioengineering marvel. Seems simple, but it isn't... or it is, but it took a heck of a lot of work to make it simple.
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Post by jpg on Sept 6, 2014 15:49:55 GMT -5
4balance... that article has some details such as the range of molecular weights suitable for drugs that I never seem to have at hand when I want to cite them... thanks. Not withstanding the scandalous conflating of blue and purple that is... have they no scientific ethics? or proper photoshop calibration files? I hate to think the heyday the shorts will have when Adam F. uncovers this fraud in a lengthy article. The whole platform really is a bioengineering marvel. Seems simple, but it isn't... or it is, but it took a heck of a lot of work to make it simple. The engineering seems elegant and innovative but would probably be very easy to copy or imitate while bypassing IP I would guess. This, in my mind decreases the value of this particular part of the IP considerable. Inhaling stuff has been around for a while and the physics it is based on is not exactly cutting edge. Again the use of the audio feedback is very elegant and innovative but realistically worth little in itself. The value is Technosphere. The rest are tools to make Texhnosphere user friendly. I guess I shouldn't have mentioned to blue to purple thing. You are probably right: shorts will be all over this... Actually it would be a great marker of short desperation if it was ever mentioned. JPG
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Post by 4Balance on Sept 6, 2014 18:09:57 GMT -5
I agree...the innovation lies in Technosphere, not the device.
But have we determined whether the FDA has approved MNKD to offer the Cricket with Afrezza...??
--4B
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Post by 4Balance on Sept 6, 2014 18:46:17 GMT -5
Ok...other threads say Cricket has not been approved for Afrezza...I'll be content with that answer.
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Post by biotec on Sept 6, 2014 19:01:52 GMT -5
Ok...other threads say Cricket has not been approved for Afrezza...I'll be content with that answer. The Cricket is not FDA approved. The Cricket has nothing to do with Afrezza!! The Cricket will not play a roll in Afrezza.The Cricket is years away from any form of Delivery.
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