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Post by agedhippie on Feb 17, 2023 9:22:45 GMT -5
UCLA would be a good choice. It has a good profile and I seem to remember they have worked together in the past (but I might be imagining that).
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Post by agedhippie on Feb 17, 2023 9:19:24 GMT -5
Isn’t joslin juvenile diabetes… would they be likely to start there ? That would be the jackpot. I don't think it would be them as they tend more towards pure research. Although they do have to support clinical trials so it's not impossible.
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Post by agedhippie on Feb 16, 2023 15:28:58 GMT -5
So you raise a good point - additional severe hypos which are nearly doubled. That IMO is a show stopper. In the trial, there was a statistically significant higher estimated rate of severe or clinically significant hypoglycaemia (blood glucose below 3 mmol/L) with 19.93 events per patient year exposed to once-weekly insulin icodec and 10.37 events per patient-year exposed to insulin degludec. From Mike's comments he said MNKD is very excited about the use of afrezza with icodec. Did MNKD just do a pilot on their own or did they work with NVO on this? I would think doubling severe hypo's makes this a non-starter for most endo's and even more so for GPs. What the primary target is for icodec I am not sure. I can see a real benefit for the T2s who are going to put on a basal. However, adding the prandial points us more toward the T1s. As Aged said, would NVO consider having afrezza compete against Novolog and Fiasp? I guess I could argue Fiasp has not lived up to the expectations NVO had for it. Would NVO be OK with afrezza taking some of the Novolog business? They were with Fiasp. UTHR was ok with Tyvaso DPI. I guess if they see afrezza more than the "niche" drug and has the potential many of us believe maybe they would be more than OK. One thing for sure is Mike said MNKD has a partner for the Big pump study ... I wouldn't get excited about the hypoglycemia numbers. This is a good example of why it's important read the report and not just the PR. The variance in the hypoglycemia numbers happened because the first dose for the half the Icodec arm was doubled with a big spike in the first two weeks. In the other half where the first dose wasn't doubled Icodec has significantly lower than Tresiba. Right now I don't believe the label is set so my expectation is that the label will not advocate doubling that first dose. This is a mechanical problem with how basal works and endos know how to fix that. Novo Nordisk doesn't care if you buy Fiasp or Novolog, the price is the same. They just care that you buy one of them, they don't want you buying something else. My suspicion is that the partner is a high profile clinic.
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Post by agedhippie on Feb 16, 2023 13:03:27 GMT -5
... Now im no doctor but i wonder if the lows were a result of "stacking" due to the long duration of the RAA, if however they used afrezza for the meal time control my assumption would be that the likelihood of lows would be greatly reduced because of the "fast out" nature of afrezza. ... No, it's not due to stacking since both arms use the same RAA, only the basal was changed.
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Post by agedhippie on Feb 16, 2023 12:58:06 GMT -5
... Adding afrezza to Tresiba or icodec is a no-brainer and no matter what Aged says few like wearing a pump and if Tresiba/afrezza get them close (75% TIR instead of 76%) and no concerns the pump goes bad while they sleep and better post prandial control. IDK I think its a winner. It makes sense for NN to go after the T1s first and then figure out the T2 plan. This is 180degress different than Sanofi's plan was. I think this could be a winner. Lets keep this honest, I have never said that anyone likes wearing a pump just as nobody likes wearing a CGM. What I have said is that the trade off can make a pump worthwhile, but LIKE? Nah, not even close. As for pumps going bad; the real risk is occlusions (the rest is just noise) - blockage in the tube stopping the insulin flow. That's why I would go for the Omnipod even though I don't like the idea of something stuck to me, but I got over the CGM so I dare say I could get over the pump if I had to.
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Post by agedhippie on Feb 16, 2023 12:38:43 GMT -5
He mentioned a successful first study with Tresiba for a pump replacement combination a little earlier. Maybe a follow on with Novo Nordisk? Who the partner is and what they are partnering for should be interesting. Nova Nordisk makes both Tresiba and icodec. Mike has mentioned a lot in the past that he is excited about the once weekly basal. Novo Nordisk would probably like to replace the pumps with Tresiba/icodec. On the other hand they also make Ozempic. Afrezza could replace that or be added to it. Mike mentioned they did proper dosing in India so results should be even better than Affinity 2. I am not sure Novo Nordisk wants Ozempic replaced unless they think Mounjaro will significantly eat into the GLP1 market. Maybe they show Ozempic plus afrezza beat Mounjaro. I heartily agree with this. There is no way I can see Novo Nordisk is the partner since in addition to the Ozempic (the largest selling GLP-1 and 6th largest prescription drug by Rx dollars last I looked), but they also make Novolog and Fiasp which which pretty much split the RAA market with Lilly. I cannot see them encouraging the use of Afrezza.
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Post by agedhippie on Feb 14, 2023 18:45:42 GMT -5
Aged - if it were possible you would not get 76% you would get 100%. Right now they are missing 24% of the time and they are using 180 as the upper limit. Use 140 and what does that number look like? Not good. How many years has Lane been working on this??? Why is he now working with MNKD? Lets see the AGPs from the ABC Study. Mike sounded very very happy with the results and is putting the big study together now. With afrezza you get constant absorption at nearly the speed of the pancreas. The only variable with afrezza is the amount hitting the deep lung. If you need another puff at 1 hr you take it. No fuss or fear of a hypo. Carb counting not required. I will say you seem to be the world's biggest proponent of pumps who doesn't use one themselves. My cousin died when his malfunctioned. A shot of Tresiba and a few puffs of afrezza during the day if only nearly as good as a pump is a much better way to go. Mike said the kids at the camp hated the pumps. The thing is once the kids start using afrezza they are not going back. You don't need to be perfect, you just need to be good enough. Right now Medtronics can hit 76%, what can Afrezza + Tresiba hit? The answer is in STAT. A 76% TIR translates to a sub-7.0 A1c (I am not sure what, just that 70% TIR equates to 7.0) Lane has been working on this probably for a decade would be my guess. I suppose you could look at his LinkIn profile if you really wanted to know. Why is he (or rather Nudge BG) working with MNKD? Because they have hired Nudge BG to use their model for the MIDD filing. The ABC study is useful as a guide to the protocols for a real trial. In itself it's not going to change anything because the number of participants is so small. THe Afrezza + pump arm is particularly interesting. I don't like pumps, but there will come a point where the gains mean I will fold and get one. We are not there yet, but the Tidepool Loop may be close. My focus is on having as little to do with my diabetes as possible so one meal time shot vs. a meal time plus later puff is not doing it - you just doubled my involvement. If I can just tee shirt size meals with Loop then I am getting interested.
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Post by agedhippie on Feb 14, 2023 8:19:51 GMT -5
Lol. Just because Al Mann couldn't write a pump algorithm doesn't mean it's impossible. Lane got the algorithm sorted for the Medtronics and Bigfoot AID pumps, and Mannkind is paying for access to it for MIDD. The Medtronics 780G has a real world 76% TIR based on 4,000+ users. I suspect this is why Mike has that use case of the AID pumps and Afrezza in the ABC trial, I think he is looking at using Afrezza as a supplement to the pump. It's impossible without more sensors and constant absorption. What Lane found out is he can't beat afrezza for post meal control. Its a damn "pocket pancreas" to quote Bill. The pumps are fine when people are sleeping which juices the TIR numbers. If it was impossible you wouldn't get 76% TIR as opposed to the numbers we saw for Afrezza in STAT. Lane and his team are just better at the algorithms than Al Mann which is unsurprising since the tools are continually improving. Now you are going to blame the night time and the basal for the STAT results so lets look at the just numbers during the day for the 780G - TIR is 73.9%. Remember, this isn't a cherry picked group. It is people using the carelink system so a group of 4000+random and unsupervised people. I would love to know why you think Lane reckons you cannot beat Afrezza for post-meal control as I can't find that source for that.
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Post by agedhippie on Feb 14, 2023 8:00:00 GMT -5
Supplement to the pump. Exactly right. I think this may work now whereas a couple of years ago it was a non-starter. The change is the sophistication of the pump algorithms. The older algorithms needed to know everything and have oversight of everything so when you introduced external insulin, RAA or Afrezza, it threw the algorithm off. Now the algorithms are much better about not making assumptions and dealing what is in front of them. It's a side effect of the move to making meal time notifications redundant (the pump just sees a rise and deals with it.)
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Post by agedhippie on Feb 13, 2023 22:53:56 GMT -5
... Think about how they are actively advocating for systems which could put them out of business, and think about what the market makers and regulators are advocating. Who seems more trustworthy? That depends if they ever expect change to come. If not advocating for the change is just self-promotion because they never expect to pay the price.
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Post by agedhippie on Feb 13, 2023 22:47:32 GMT -5
If that algorithm could have been written Al Mann would have written it. Lane is never getting that algorithm sorted out because absorption is too unpredictable. It wasn't like Al did not try. This is the guy who perfected the solar panel, the pacemaker and the insulin pump. We have afrezza because he knew the insulin was too damn unpredictable for an algorithm. You do know the growing tag line for pump users don't you??? "Dump the pump and get the afrezza" Aged, save your time and money on the pump, just go here and they will help you out insulinsavings.com Lol. Just because Al Mann couldn't write a pump algorithm doesn't mean it's impossible. Lane got the algorithm sorted for the Medtronics and Bigfoot AID pumps, and Mannkind is paying for access to it for MIDD. The Medtronics 780G has a real world 76% TIR based on 4,000+ users. I suspect this is why Mike has that use case of the AID pumps and Afrezza in the ABC trial, I think he is looking at using Afrezza as a supplement to the pump.
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Post by agedhippie on Feb 13, 2023 22:35:09 GMT -5
RAA's peak at 2 hours after given subq. The only time that algorithm works well is between the breakfast dose and lunch. Algorithm better not skip a meal. agedhippie , last time you mentioned it, oh pump master you were giving subq per needle after your meals. Same plan of care oh aged one? No CMG..... I am using a CGM (back on Dexcom thankfully), but I am still on pens. My endo would dearly love to get me on a pump (Omnipod 5 for choice), but want to be sure whatever I get can run the Tidepool Loop software. Right now all the pumps use the Dexcom G6 and I really want the G7 which comes out in a few days so they need to do the integration work. TBH I am not sure why they haven't done that already. The upside to the Omnipod would be no big upfront cost like with the Tandem pump so if i don't like it I could always just dump it. TLDR: I am on a CGM, but not on a pump. However, that might change in the next year or so.
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Post by agedhippie on Feb 13, 2023 16:48:38 GMT -5
Great point, and as far as MNKD is concerned, we'd have to have implicit knowledge that naked shorting is indeed happening and that there is something that can be done about it. The question then becomes, does anyone know for a fact that it is happening? And then how do we prove it? And then what can be done about it? Market makers are allowed to short without first securing shares, so it happens for all stocks. What could be done about it?... you can lobby your politicians to change laws, but that's a steep climb as those that participate in the markets would likely view that as a negative for liquidity. If you're worried that somehow your broker doesn't actually have shares that you could vote and would pay you dividends if they are ever declared... call them and ask what level of open fail to deliver exist for MNKD holdings in their custody. They certainly could provide that info, though you might need to be insistent. That would be a sanity check as to whether the data on open fail to deliver is accurate, or totally off the mark as some like to claim here. This is a useful reference - www.sec.gov/investor/pubs/regsho.htm#:~:text=A%20failure%20to%20deliver%20occurs,securities%20on%20the%20settlement%20date.
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Post by agedhippie on Feb 13, 2023 16:35:54 GMT -5
My wife has a cousin who's youngest son was diagnosed T1 very early. It aged her. She is one of the few people I've met who had heard about Afrezza before I told them. She was interested in a pediatric trial. This was like 8 years ago. Her son is now a young teenager. He had a pump. Her father, her son's grandfather was also a T1, and wore a pump. He went blind, lost toes, and died from COVID. There are worse things than trying to watch your BG levels and using ultra-fast inhalable human insulin as a tool in the toolbox to better manage health. It doesn't surprise me that she found out about Afrezza. The attitude I have heard (we used to run support groups for partners and parents) is that they feel in some way it's their fault and they will burn themselves out trying to fix it. Our sample may have been biased because these were people motivated (and/or desperate) enough to come to a support group. There are reasons to be optimistic. A lot of the data we see is out of date now because treatments have moved on so far (we no longer use animal insulins or NPH, or [spit] ultralente.) Those insulins dictated your life which is why everyone jumped on RAA. Suddenly you could eat when you wanted to and not when your insulin allowed or demanded it. TIR was just awful which led to the complications years later. The AID pumps are another jump like RAA which is why people want them. Now I can ignore my diabetes between meals and let the system keep everything level. Once Lane Desborough who sayhey talks about gets the algorithm sorted out I won't even have to bother with meals - the system will do that as well and now I can really ignore my diabetes. Oddly the thing that stops me from getting one is that progress is so fast that I don't want to get one that will effectively be obsolete in a couple of years (one reason I find the DIY APS movement attractive.)
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Post by agedhippie on Feb 13, 2023 14:15:47 GMT -5
The pump sounds cumbersome and technical… and has quality issues being addressed from a Legal safety standpoint… looks like if MIKES abc trails go well ,why would that combination not be a home run for The market he intends it for … regardless if it takes somewhat longer .. should be interesting. Mike's last comment on the pilot was it was going really well and they are planning for a big study. He made the comment about going to a kids diabetes camp and how the kids hated their pumps at the camp. He said it was a real eye opener for him. There are about 95k pump users today with the highest rates in the youngest patients. I am not sure why that is but over 90% of preschoolers use a pump. Given the numbers the kids afrezza study and the ABC study go hand in hand. Kids hate pumps because it makes them not like other kids, ditto MDI and my bet is Afrezza as well. There are some really unpleasant numbers around kids and diabetes - 39% have PTSD symptoms, and 66% have traumatic exposure. Making kids responsible for managing their diabetes is unlikely to help that number. You cannot pass that responsibility to the parents because they work and cannot be there all the time (one reason remote CGM monitoring became so popular.) The view I hear from endos is that anything which removes kids from responsibility lessens that trauma, and parents cannot be there 24x7 so they worry about what happens when they aren't. Reasons like these are why endos prescribe pumps for kids, especially pre-schoolers. You really don't want a 3 or 4 year old taking responsibility for their levels. Pumps, and especially AID pumps, fix this problem to a large degree. Later you will find that teenage kids going through the rebellious phase are less than zealous about bolusing as well so it's better to let the pump do it. Late edit: Some stats for mothers with type 1 kids; 10% have full blown PTSD, another 15% had partial PTSD. This whole area is hugely under appreciated because diabetes is so often regarded purely from a mechanical lens.
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