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Post by matt on May 10, 2020 7:30:18 GMT -5
Honestly, it should be common sense that . . . Common sense is not the same as scientific evidence. When the link was first documented between cholesterol levels and the incidence of heart disease the American Heart Association thought it was common sense to go on a crusade to lower the dietary intake of cholesterol by having people reduce their consumption of eggs and other high cholesterol foods. Fast forward thirty years and by then it was known that most patients with high cholesterol levels are refractory to dietary interventions since the largest component of hyperlipidemia is genetic. Meanwhile, the major food processors jumped on the bandwagon and tried to reduce production of food with a large amount of healthy fats. Problem is that when you take fat out of foods they taste bland so the manufacturers had to replace fats with salt and sugar to make their food taste better. Many physicians now assign much of the blame for the nations obesity epidemic and increased incidence of untreated hypertension on the "common sense" AHA recommendations to eliminate dietary cholesterol, not 100% of the blame, but a major part. The medical community learned their lesson well on this point and will never again recommend sweeping changes in the SOC for any disease without hard evidence that the new standard provides better results than the old standard. Good science does not cut corners. |
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Post by sellhighdrinklow on May 10, 2020 8:13:41 GMT -5
Honestly, it should be common sense that . . . Common sense is not the same as scientific evidence.Ā When the link was first documented between cholesterol levels and the incidence of heart disease the American Heart Association thought it was common sense to go on a crusade to lower the dietary intake of cholesterol by having people reduce their consumption of eggs and other high cholesterol foods.Ā Fast forward thirty years and by then it was known that most patients with high cholesterol levels are refractory to dietary interventions since the largest component of hyperlipidemia is genetic. Meanwhile, the major food processors jumped on the bandwagon and tried to reduce production of food with a large amount of healthy fats.Ā Problem is that when you take fat out of foods they taste bland so the manufacturers had to replace fats with salt and sugar to make their food taste better.Ā Many physicians now assign much of the blame for the nations obesity epidemic and increased incidence of untreated hypertension on the "common sense" AHA recommendations to eliminate dietary cholesterol, not 100% of the blame, but a major part.Ā The medical community learned their lesson well on this point and will never again recommend sweeping changes in the SOC for any disease without hard evidence that the new standard provides better results than the old standard.Ā Good science does not cut corners. Common sense and science dictated that CGMs should have been protocol/SOC for all diabetics long ago but it's just recently that CGMs have gained full acceptance. It's also about MONEY and the bowing to the ADA to get that SOC designation. How else would one explain delaying results of studies that might or would move the needle ...say, to move Afrezza closer to a preferred status / SOC w the ADA? Waiting for the ADA convention? Wow! Defies logic and it's B S IMHO. |
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Post by agedhippie on May 10, 2020 9:24:20 GMT -5
Common sense and science dictated that CGMs should have been protocol/SOC for all diabetics long ago but it's just recently that CGMs have gained full acceptance. It's also about MONEY and the bowing to the ADA to get that SOC designation. How else would one explain delaying results of studies that might or would move the needle ...say, to move Afrezza closer to a preferred status / SOC w the ADA? Waiting for the ADA convention? Wow! Defies logic and it's B S IMHO. The studies are delayed because Mannkind has not funded them. Do the trial, get the results, and the rest follows. No trials, no change. The rules are very clear. The issue with CGMs for Type 2 is that there are three very large studies that say tight blood control is less important for Type 2 than it is for Type 1 (ADVANCE, VADT, and ACCORD). Dexcom is starting to run trials now to try establish that there are long term benefits. Insurers are starting to consider Libre as an alternative to strips since the costs are comparable, but it's going to need to get a lot more accurate (in my more paranoid moments I have run both in parallel and Dexcom is far more accurate). Libre is good for retrospective use where you are looking at how the day went and the shape of the curve is what is important, but personally I would never dose off a Libre as the realtime part sucks for me. |
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Post by sportsrancho on May 10, 2020 11:07:18 GMT -5
Iāve been told that WAY over half of diabetics donāt even know what a CGM is.
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Post by mango on May 10, 2020 11:58:53 GMT -5
Common sense and science dictated that CGMs should have been protocol/SOC for all diabetics long ago but it's just recently that CGMs have gained full acceptance. It's also about MONEY and the bowing to the ADA to get that SOC designation. How else would one explain delaying results of studies that might or would move the needle ...say, to move Afrezza closer to a preferred status / SOC w the ADA? Waiting for the ADA convention? Wow! Defies logic and it's B S IMHO. The studies are delayed because Mannkind has not funded them. Do the trial, get the results, and the rest follows. No trials, no change. The rules are very clear. The issue with CGMs for Type 2 is that there are three very large studies that say tight blood control is less important for Type 2 than it is for Type 1 (ADVANCE, VADT, and ACCORD). Dexcom is starting to run trials now to try establish that there are long term benefits. Insurers are starting to consider Libre as an alternative to strips since the costs are comparable, but it's going to need to get a lot more accurate (in my more paranoid moments I have run both in parallel and Dexcom is far more accurate). Libre is good for retrospective use where you are looking at how the day went and the shape of the curve is what is important, but personally I would never dose off a Libre as the realtime part sucks for me. They did not design those trials properly, aged. First, they did not use CGMs to assess real-time blood glucose levels, secondly, they focused on A1cāa proxy, and an inaccurate reflection of glucose homeostasis. In the ACCORD trial there was a 3-fold increase in severe hypoglycemic events requiring third party or medical assistance. Intensive use with RAAs leads to significantly more hypoglycemic events and time in that rangeāwhich artificially lowers the A1c, giving a false and inaccurate assessment kn glucose homeostasis! Even though these T2Ds were intensively treated with insulin, we all know that RAAs just do not compare to the PK/PD profile of Afrezza and it is totally disingenuous and inaccurate to assume those trials are the end all be all. MannKind chooses to incorporate CGMs into their trials because TIR is of utmost importance and is a truest, most accurate reflection of glucose homeostasis in real time that one can currently achieve in these settings. How often was blood glucose checked everyday during those trials? Not using a CGM for something like that with intensive insulin treatment was a significant and major flaw of the trial designs. Without the CGM they were unable to assess how often and how long people were in hyperglycemia. What is the explanations for the increased CVD deaths with intensive glycemic control in ACCORD? Randomization to the intensive arm was associated with thiazolidinediones, other drugs, and drug combinations and greater weight gain. It is biologically plausible that severe hypoglycemia could increase the risk of cardiovascular death in participants with high underlying CVD risk. This might be further confounded by the development of hypoglycemia unawareness, particularly in patients with coexisting cardiovascular autonomic neuropathy (a strong risk factor for sudden death). Death from a hypoglycemic event may be mistakenly ascribed to coronary artery disease, since there may not have been a blood glucose measurement and since there are no anatomical features of hypoglycemia detected postmortem.
Other plausible mechanisms for the increase in mortality in ACCORD include weight gain, unmeasured drug effects or interactions, or the āintensityā of the ACCORD intervention (use of multiple oral glucose-lowering drugs along with multiple doses of insulin, frequent therapy adjustments to push A1C and self-monitored blood glucose to very low targets, and an intense effort to rapidly reduce A1C by ā¼2% in participants entering the trial with advanced diabetes and multiple comorbidities).www.ncbi.nlm.nih.gov/pmc/articles/PMC2606812/ |
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Post by agedhippie on May 10, 2020 15:28:21 GMT -5
The studies are delayed because Mannkind has not funded them. Do the trial, get the results, and the rest follows. No trials, no change. The rules are very clear. The issue with CGMs for Type 2 is that there are three very large studies that say tight blood control is less important for Type 2 than it is for Type 1 (ADVANCE, VADT, and ACCORD). Dexcom is starting to run trials now to try establish that there are long term benefits. Insurers are starting to consider Libre as an alternative to strips since the costs are comparable, but it's going to need to get a lot more accurate (in my more paranoid moments I have run both in parallel and Dexcom is far more accurate). Libre is good for retrospective use where you are looking at how the day went and the shape of the curve is what is important, but personally I would never dose off a Libre as the realtime part sucks for me. They did not design those trials properly, aged. First, they did not use CGMs to assess real-time blood glucose levels, secondly, they focused on A1cāa proxy, and an inaccurate reflection of glucose homeostasis. In the ACCORD trial there was a 3-fold increase in severe hypoglycemic events requiring third party or medical assistance. Intensive use with RAAs leads to significantly more hypoglycemic events and time in that rangeāwhich artificially lowers the A1c, giving a false and inaccurate assessment kn glucose homeostasis! Even though these T2Ds were intensively treated with insulin, we all know that RAAs just do not compare to the PK/PD profile of Afrezza and it is totally disingenuous and inaccurate to assume those trials are the end all be all. MannKind chooses to incorporate CGMs into their trials because TIR is of utmost importance and is a truest, most accurate reflection of glucose homeostasis in real time that one can currently achieve in these settings. How often was blood glucose checked everyday during those trials? Not using a CGM for something like that with intensive insulin treatment was a significant and major flaw of the trial designs. Without the CGM they were unable to assess how often and how long people were in hyperglycemia. What is the explanations for the increased CVD deaths with intensive glycemic control in ACCORD? Randomization to the intensive arm was associated with thiazolidinediones, other drugs, and drug combinations and greater weight gain. It is biologically plausible that severe hypoglycemia could increase the risk of cardiovascular death in participants with high underlying CVD risk. This might be further confounded by the development of hypoglycemia unawareness, particularly in patients with coexisting cardiovascular autonomic neuropathy (a strong risk factor for sudden death). Death from a hypoglycemic event may be mistakenly ascribed to coronary artery disease, since there may not have been a blood glucose measurement and since there are no anatomical features of hypoglycemia detected postmortem.
Other plausible mechanisms for the increase in mortality in ACCORD include weight gain, unmeasured drug effects or interactions, or the āintensityā of the ACCORD intervention (use of multiple oral glucose-lowering drugs along with multiple doses of insulin, frequent therapy adjustments to push A1C and self-monitored blood glucose to very low targets, and an intense effort to rapidly reduce A1C by ā¼2% in participants entering the trial with advanced diabetes and multiple comorbidities).www.ncbi.nlm.nih.gov/pmc/articles/PMC2606812/ACCORD doesn't seem quite right to me either. I can't help feeling that there was some other factor there that they missed. The problem is unless it can be identified the results stand. I am less concerned with co-morbidities because they are so common (CDC says over 60% of the US population and since they tend to arrive later in life the probability is that most of the participants will have at least one, and Type 2 comes with a high probability of either high blood pressure or triglycerides) Since these trials were all evaluated against A1c the frequency of testing is not material. What there were looking at was the long term outcomes, not the short term control. Yes the two are linked, but they can also be evaluated in isolation which is what happened there. The conclusion was that tight control in Type 2 does not as significantly impact on the likelihood of complications. Until someone proves otherwise those trials are the reference. There is work starting now to prove that TIR is the control factor, but until they are completed TIR remains unproven. This is all being driven by the artificial pancreas program and funded by that research. Since they are longitudinal studies results are going to be at least five years out (it takes at least that long for complications to develop). I remember when the ACCORD study came out because my endo at the time tried to get me to relax my control because the risk curve was U shaped according to ACCORD. We agreed to differ... |
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Post by agedhippie on May 10, 2020 15:31:45 GMT -5
Iāve been told that WAY over half of diabetics donāt even know what a CGM is. Easily. CGMs are still very much a minority item. I suspect that most Type 2 diabetics don't even test once a day based on my conversations. |
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Post by Deleted on May 10, 2020 19:47:21 GMT -5
Iāve been told that WAY over half of diabetics donāt even know what a CGM is. Easily. CGMs are still very much a minority item. I suspect that most Type 2 diabetics don't even test once a day based on my conversations. It's safe to say 80% of Type 2 Diabetics who are on Oral Meds do not test their BG Levels on a regular basis. |
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Post by sportsrancho on May 11, 2020 5:29:04 GMT -5
Stock analysts at SVB Leerink lowered their FY2023 EPS estimates for shares of MannKind in a report issued on Thursday, May 7th. SVB Leerink analyst T. Smith now expects that the biopharmaceutical company will post earnings of $0.04 per share for the year, down from their prior estimate of $0.11. SVB Leerink also issued estimates for MannKindās FY2024 earnings at $0.13 EPS.
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Post by hellodolly on May 11, 2020 5:48:00 GMT -5
Stock analysts at SVB Leerink lowered their FY2023 EPS estimates for shares of MannKind in a report issued on Thursday, May 7th. SVB Leerink analyst T. Smith now expects that the biopharmaceutical company will post earnings of $0.04 per share for the year, down from their prior estimate of $0.11. SVB Leerink also issued estimates for MannKindās FY2024 earnings at $0.13 EPS. Figured that was coming considering the pandemic is going to force a lot of analysts to change expectations. How long until you think we see an upward revision? |
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Post by Deleted on May 11, 2020 6:07:25 GMT -5
Stock analysts at SVB Leerink lowered their FY2023 EPS estimates for shares of MannKind in a report issued on Thursday, May 7th. SVB Leerink analyst T. Smith now expects that the biopharmaceutical company will post earnings of $0.04 per share for the year, down from their prior estimate of $0.11. SVB Leerink also issued estimates for MannKindās FY2024 earnings at $0.13 EPS. 2024 estimates seem very low. Let's say TreT alone brings in $100M in Revs and O/S is 400M that's $ .25 eps. Am I missing something?? |
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Post by sportsrancho on May 11, 2020 6:12:49 GMT -5
Stock analysts at SVB Leerink lowered their FY2023 EPS estimates for shares of MannKind in a report issued on Thursday, May 7th. SVB Leerink analyst T. Smith now expects that the biopharmaceutical company will post earnings of $0.04 per share for the year, down from their prior estimate of $0.11. SVB Leerink also issued estimates for MannKindās FY2024 earnings at $0.13 EPS. Figured that was coming considering the pandemic is going to force a lot of analysts to change expectations.Ā How long until you think we see an upward revision?Ā I think there is already from another analyst Iāve got to go find it. MannKind Co. (NASDAQ:MNKD) ā Equities research analysts at Oppenheimer lifted their FY2020 EPS estimates for shares of MannKind in a research note issued on Thursday, May 7th. Oppenheimer analyst S. Lichtman now anticipates that the biopharmaceutical company will earn ($0.18) per share for the year, up from their previous forecast of ($0.20). MannKind Co. (NASDAQ:MNKD) ā Analysts at Cantor Fitzgerald cut their FY2020 earnings per share estimates for shares of MannKind in a research note issued on Thursday, May 7th. Cantor Fitzgerald analyst B. Folkes now anticipates that the biopharmaceutical company will post earnings of ($0.21) per share for the year, down from their prior estimate of ($0.18). |
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Post by awesomo on May 11, 2020 9:44:50 GMT -5
Stock analysts at SVB Leerink lowered their FY2023 EPS estimates for shares of MannKind in a report issued on Thursday, May 7th. SVB Leerink analyst T. Smith now expects that the biopharmaceutical company will post earnings of $0.04 per share for the year, down from their prior estimate of $0.11. SVB Leerink also issued estimates for MannKindās FY2024 earnings at $0.13 EPS. 2024 estimates seem very low. Let's say TreT alone brings in $100M in Revs and O/S is 400M that's $ .25 eps. Am I missing something?? Earnings per share uses net income, not revenue. You have to factor in the expenses. |
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Post by Deleted on May 11, 2020 10:52:24 GMT -5
2024 estimates seem very low. Let's say TreT alone brings in $100M in Revs and O/S is 400M that's $ .25 eps. Am I missing something?? Earnings per share uses net income, not revenue. You have to factor in the expenses. I know but TreT Revenue is ROYALTIES so depending on how they do the accounting it could fall straight to the bottom line. |
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Post by radgray68 on May 11, 2020 12:11:41 GMT -5
Looks like we've been set up now to have a large string of revenue beats. We just have to execute and every quarterly report becomes sort of a catalyst. I'm alright with it, I guess.
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