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Post by boytroy88 on May 19, 2017 17:46:36 GMT -5
In my view, the meeting's main message was to thank investors who've been long in the stock. The term, 'we will get there' was echoed more than once and by all who presented to the audience. This was not an 'announcement meeting' that many had perhaps hoped for. It was more than that. The real life stories which were shared by four Type 1 diabetics was poignant. That they also have a sincere interest in supporting Afrezza's success is as important to them as the air you and I breathe. Yes. They are determined. You should be glad for that. The singular message they shared which was fully embraced by those in the audience and I paraphrase: 'Afrezza cannot and will not disappear. We will do all in our power to make sure of that.' I believe it. These Type 1 diabetics stand 'at the ready' to use their star power to reach out to diabetics and in a manner to honor and ensure Al Mann's legacy is protected from the inherent cancerous maladies of our healthcare system. Be assured, this has never been done before. It hasn't. The audience saw perhaps for the first time, that Afrezza will change the world for diabetics and for the better. My thoughts in a nutshell - if there is one - thank God for their earnest desire to help people who suffer with the same disease as they do. Interestingly, one of the diabetics on stage mentioned that he was in the early stages of working on circumventing 'the system' we have in place today. He's experienced it and wants to see it improve for patients. No argument from the attendees on this point. I applaud his disruptive thinking which put me in mind of the American Revolution. If it's NOT working for you then organize with others to CHANGE IT. We'll have to see whether he succeeds or not. Too early to tell. In short, his lofty and noble idea includes drop shipping Afrezza on a subscription basis right to your door. Isn't stability at room temperature marvelous? Fluctuations in outside temps can be dealt with fairly easily. Ever ordered an Omaha Steak? Following the meeting, what I learned from speaking to Matt, Mike and Ray were as follows and each confirms points I've made here before: 1) The exit of Sanofi was a disaster for the company and one of such proportions that the FALL OUT continues to this day amongst endocrinologists. Yes. The fall out from this action continues to this day. To. This. Day. 2) Those who were in charge for the drug development program at MannKind are no longer with the company. They completely missed the boat on the importance of titration of insulin. Do you wonder why the drop out in the clinical trials occured as it did? You shouldn't. Mike has worked with Ray and manufacturing to address this issue. The new titration packs are now available for this important step in treatment with Afrezza. 3) In addition to the above, the 4 week study on clinicaltrials.gov mimics the information provided by the Type 1 diabetics on stage who saw real results in 4 weeks. You can surmise for yourselves how results of this study might play out amongst the providers of this historic insulin. clinicaltrials.gov/ct2/show/NCT03143816?term=Technosphere+Insulin&rank=84) Another study is in the works not yet posted. Ray did not share the details but we already know that additional studies are being reviewed for submission. Pediatrics being one of them. 5) Matt is fully aware of the cash runway BUT he has three priorities he is focused on in the near term. Raising cash is not one of them at least not yesterday. You can surmise what that could mean. I suspect that if the three priorities he's currently working on come to fruition, obtaining cash won't be an issue which I've said on this board too. And to be clear, their cash runway in not dry as of yesterday's meeting. IT isn't. The DTC campaign will launch in July as it should. By then, endocrinologists will know full well that Afrezza is here to stay. Period. End of Quote. Let the disruption begin. There you have it. Aside from the vote and the speakers, the audience was provided a sneak peek at the upcoming DTC campaign videos. Very effective and in my view, equally as disruptive as Afrezza is. One statement from one of the type 1 diabetic speakers stood out to me and is with me today and I paraphrase: 'Being a diabetic is like being on a boat that is sinking. You've got a captain and the crew around you sure, but when the time comes, they get to jump ship and it's just you who's going down.' Well said. For me, the picture couldn't be any clearer so I remain tied to my shares and the belief that this drug will change the world of diabetes. So now we must wait to see if all that's been put in place since last year by Matt, Mike and Ray and by Stuart and Jason this year will bear fruit. There is NO other option. We must be patient. I had planned on not getting anymore shares till I see a definite turnaround but your post pretty much changed my mind. Regardless of whether I'm right or wrong in my purchase I became an even firmer believer after your post. Thank you! Hoptimist (nut jobs) Unite!!
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Post by ssiegel on May 20, 2017 9:58:31 GMT -5
Thanks, Tinkerbell !
I agree that the lack of an effective titration protocol (#2 on your list) was a HUGE miss for this company. Alfred Mann unabashedly proclaimed to anyone who would listen that Technospere insulin is completely unlike injectable insulin, whether RAAs or regular. Yet the scientists at MannKind decided to use a titration protocol comparable to titrating RAA insulin.
That, IMHO, set them way back in the eyes of endos. As much as I dislike Sanofi-Aventis, they were saddled with this titration protocol and when endos reported poor results using Afrezza, that likely played into their decision to walk away rather than damage their reputation among physicians.
Regardless, I think MannKind is on the right track with the new titration packs and post-meal adjustment study data. The problem is that there is no new titration protocol. The titration packs contain the same instructions as the others. Mannkind can't change the label instructions without some sort of trial demonstrating that a new protocol is safe and effective.
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Tinkerbell
Researcher
Watcher of the Skies
Posts: 143
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Post by Tinkerbell on May 20, 2017 12:37:26 GMT -5
Thanks, Tinkerbell !
I agree that the lack of an effective titration protocol (#2 on your list) was a HUGE miss for this company. Alfred Mann unabashedly proclaimed to anyone who would listen that Technospere insulin is completely unlike injectable insulin, whether RAAs or regular. Yet the scientists at MannKind decided to use a titration protocol comparable to titrating RAA insulin.
That, IMHO, set them way back in the eyes of endos. As much as I dislike Sanofi-Aventis, they were saddled with this titration protocol and when endos reported poor results using Afrezza, that likely played into their decision to walk away rather than damage their reputation among physicians.
Regardless, I think MannKind is on the right track with the new titration packs and post-meal adjustment study data. The problem is that there is no new titration protocol. The titration packs contain the same instructions as the others. Mannkind can't change the label instructions without some sort of trial demonstrating that a new protocol is safe and effective. Yes I totally understand and appreciate the point you've made. However, in the real world, an ultra rapid inhalable insulin like any RAA must be adjusted to supply each individual's needs. Any approved drug may be adjusted up or down from recommended dosing or protocol for that matter because individual biology in fact plays a role in how the drug behaves once in a person's system. While it's true that the majority may be able to achieve results according to a label, under a physician's care, this may be adjusted as needed. There is significant information in the market place that confirms Afrezza must be adjusted as needed by each diabetic. In short, screw the label if what it says is not working for me but a modification of it does. This is not being prescribed off label. Right?
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Post by scoy on May 20, 2017 12:53:46 GMT -5
Thanks, Tinkerbell !
I agree that the lack of an effective titration protocol (#2 on your list) was a HUGE miss for this company. Alfred Mann unabashedly proclaimed to anyone who would listen that Technospere insulin is completely unlike injectable insulin, whether RAAs or regular. Yet the scientists at MannKind decided to use a titration protocol comparable to titrating RAA insulin.
That, IMHO, set them way back in the eyes of endos. As much as I dislike Sanofi-Aventis, they were saddled with this titration protocol and when endos reported poor results using Afrezza, that likely played into their decision to walk away rather than damage their reputation among physicians.
Regardless, I think MannKind is on the right track with the new titration packs and post-meal adjustment study data. The problem is that there is no new titration protocol. The titration packs contain the same instructions as the others. Mannkind can't change the label instructions without some sort of trial demonstrating that a new protocol is safe and effective. Aren't they working on that right now? The newest 10Q said they were allocating more money to FDA trial expenses. If you go here and search for product Afrezza: www.accessdata.fda.gov/scripts/cder/pmc/It says status "ongoing" for: Conduct a dose-ranging PK-PD euglycemic glucose-clamp trial to characterize the dose-response of Afrezza relative to subcutaneous insulin in patients with type 1 diabetes. ... These data may impact labeling recommendations
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Post by ssiegel on May 20, 2017 17:23:13 GMT -5
The problem is that there is no new titration protocol. The titration packs contain the same instructions as the others. Mannkind can't change the label instructions without some sort of trial demonstrating that a new protocol is safe and effective. Yes I totally understand and appreciate the point you've made. However, in the real world, an ultra rapid inhalable insulin like any RAA must be adjusted to supply each individual's needs. Any approved drug may be adjusted up or down from recommended dosing or protocol for that matter because individual biology in fact plays a role in how the drug behaves once in a person's system. While it's true that the majority may be able to achieve results according to a label, under a physician's care, this may be adjusted as needed. There is significant information in the market place that confirms Afrezza must be adjusted as needed by each diabetic. In short, screw the label if what it says is not working for me but a modification of it does. This is not being prescribed off label. Right? Agreed, but that's true for any drug. In afrezza's particular case, the point is that the label doesn't explain what exactly to do with the titration packs. It doesn't offer any suggestions for the best method for titration -- e.g. recheck glucose at 1-2 hours and if greater than 180, etc, etc. In other words, patients are pretty much left in the dark as to how they should go about titrating for best results.
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Post by mnholdem on May 20, 2017 18:21:53 GMT -5
It's the doctor's job to instruct their patient and there is information both the Afrezza patient and HCP websites. The patient sites says your doctor may make adjustments after your initial dose.
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Post by ssiegel on May 20, 2017 19:57:10 GMT -5
It's the doctor's job to instruct their patient and there is information both the Afrezza patient and HCP websites. The patient sites says your doctor may make adjustments after your initial dose. Absolutely, but wouldn't it be handy to the patient to have some sort of flow chart to follow with specific instructions for specific situations?
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Tinkerbell
Researcher
Watcher of the Skies
Posts: 143
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Post by Tinkerbell on May 20, 2017 20:04:15 GMT -5
Yes I totally understand and appreciate the point you've made. However, in the real world, an ultra rapid inhalable insulin like any RAA must be adjusted to supply each individual's needs. Any approved drug may be adjusted up or down from recommended dosing or protocol for that matter because individual biology in fact plays a role in how the drug behaves once in a person's system. While it's true that the majority may be able to achieve results according to a label, under a physician's care, this may be adjusted as needed. There is significant information in the market place that confirms Afrezza must be adjusted as needed by each diabetic. In short, screw the label if what it says is not working for me but a modification of it does. This is not being prescribed off label. Right? Agreed, but that's true for any drug. In afrezza's particular case, the point is that the label doesn't explain what exactly to do with the titration packs. It doesn't offer any suggestions for the best method for titration -- e.g. recheck glucose at 1-2 hours and if greater than 180, etc, etc. In other words, patients are pretty much left in the dark as to how they should go about titrating for best results. What specific information is missing from this label which is available on MannKind's website? www.afrezza.com/wp-content/uploads/2016/08/afrezza.pdf Are you saying that this information is not provided in the titration pack at all? Sorry, I don't have access to the pack.
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Post by ssiegel on May 21, 2017 9:24:52 GMT -5
Agreed, but that's true for any drug. In afrezza's particular case, the point is that the label doesn't explain what exactly to do with the titration packs. It doesn't offer any suggestions for the best method for titration -- e.g. recheck glucose at 1-2 hours and if greater than 180, etc, etc. In other words, patients are pretty much left in the dark as to how they should go about titrating for best results. What specific information is missing from this label which is available on MannKind's website? www.afrezza.com/wp-content/uploads/2016/08/afrezza.pdf Are you saying that this information is not provided in the titration pack at all? Sorry, I don't have access to the pack. There are no specific instructions on the label as to how to titrate. For comparison, look at figure 1 in this article: www.aafp.org/afp/1998/0301/p1079.htmlAlthough aimed at nurses taking care of a hospitalized diabetic, the principles would apply to an outpatient as well. Note how specific it is as to when to test blood sugar, when to administer insulin, when to do a follow up blood sugar, how much insulin to administer in each instance, etc.
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Post by peppy on May 21, 2017 9:35:26 GMT -5
What specific information is missing from this label which is available on MannKind's website? www.afrezza.com/wp-content/uploads/2016/08/afrezza.pdf Are you saying that this information is not provided in the titration pack at all? Sorry, I don't have access to the pack. There are no specific instructions on the label as to how to titrate. For comparison, look at figure 1 in this article: www.aafp.org/afp/1998/0301/p1079.htmlAlthough aimed at nurses taking care of a hospitalized diabetic, the principles would apply to an outpatient as well. Note how specific it is as to when to test blood sugar, when to administer insulin, when to do a follow up blood sugar, how much insulin to administer in each instance, etc. Heh 2 DOSAGE AND ADMINISTRATION 2.1 Route of Administration AFREZZA should only be administered via oral inhalation using the AFREZZA Inhaler. AFREZZA is administered using a single inhalation per cartridge. 2.2 Dosage Information Administer AFREZZA at the beginning of the meal. Dosage adjustment may be needed when switching from another insulin to AFREZZA [see Warnings and Precautions (5.2)]. Starting Mealtime Dose: • Insulin Naïve Individuals: Start on 4 units of AFREZZA at each meal. • Individuals Using Subcutaneous Mealtime (Prandial) Insulin: Determine the appropriate AFREZZA dose for each meal by converting from the injected dose using Figure 1. • Individuals Using Subcutaneous Pre-mixed Insulin: Estimate the mealtime injected dose by dividing half of the total daily injected pre-mixed insulin dose equally among the three meals of the day. Convert each estimated injected mealtime dose to an appropriate AFREZZA dose using Figure 1. Administer half of the total daily injected pre-mixed dose as an injected basal insulin dose. afrezza.com/wp-content/uploads/2016/08/afrezza.pdf
Mealtime Dose Adjustment Adjust the dosage of AFREZZA based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal. Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness [see Warnings and Precautions (5.3), and Use in Specific Populations (8.6, 8.7)]. Carefully monitor blood glucose control in patients requiring high doses of AFREZZA. If, in these patients, blood glucose control is not achieved with increased AFREZZA doses, consider use of subcutaneous mealtime insulin.
www.afrezza.com/wp-content/uploads/2017/03/MANTAC1015_25884_Interactive_Stay-on-Afrezza_4-0.pdf
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Post by ssiegel on May 21, 2017 9:41:50 GMT -5
Yes, but that does not instruct how to titrate. It merely tells the patient how to start and that they will need to titrate. The actual act of titration involves adjusting the dose to meet the daily need. That in turn requires measuring the sugar at specific times before and after meals, supplementing, adjusting, etc. Again I refer to figure 1 in the link I provided.
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Post by mnholdem on May 21, 2017 10:19:33 GMT -5
Self-titration algorithms require study data, which is what Eli-Lilly was required to do before the FDA would allow the company to publish their Q1D and Q3D patient self-titration for Humalog. MannKind has completed a similar study and has submitted it to the FDA Excerpt: Summary
This approach allowed us to assess the benefit/risk for each TI dosing regimen and to compare results with simulations of insulin lispro. We identified a new titration rule for TI that could significantly improve the efficacy of treatment with TI.
Link: www.ncbi.nlm.nih.gov/pubmed/27333446--- As I stated in a posted reply to Tinkerbell the other day, failure to have designed a titration protocol for physicians and/or patients prior to FDA approval was a huge failure of MannKind's medical staff. Fortunately, MannKind CMO Dr. Ray Urbanski is fixing this over sight.
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Post by peppy on May 21, 2017 10:26:00 GMT -5
Yes, but that does not instruct how to titrate. It merely tells the patient how to start and that they will need to titrate. The actual act of titration involves adjusting the dose to meet the daily need. That in turn requires measuring the sugar at specific times before and after meals, supplementing, adjusting, etc. Again I refer to figure 1 in the link I provided. Humalog 2.2 Route of Administration Subcutaneous Injection: HUMALOG U-100 or U-200 • Administer the dose of HUMALOG U-100 or HUMALOG U-200 within fifteen minutes before a meal or immediately after a meal by injection into the subcutaneous tissue of the abdominal wall, thigh, upper arm, or buttocks. To reduce the risk of lipodystrophy, rotate the injection site within the same region from one injection to the next [see Adverse Reactions (6)]. • HUMALOG administered by subcutaneous injection should generally be used in regimens with an intermediate- or long-acting insulin. Continuous Subcutaneous Infusion (Insulin Pump): HUMALOG U-100 ONLY • Do NOT administer HUMALOG U-200 using a continuous subcutaneous infusion pump. • Administer HUMALOG U-100 by continuous subcutaneous infusion into the subcutaneous tissue of the abdominal wall. Rotate infusion sites within the same region to reduce the risk of lipodystrophy [see Adverse Reactions (6.1)]. • Follow healthcare professional recommendations when setting basal and meal time infusion rate. • Do NOT dilute or mix HUMALOG U-100 when administering by continuous subcutaneous infusion. • Change HUMALOG U-100 in the pump reservoir at least every 7 days. • Change the infusion sets and the infusion set insertion site at least every 3 days. • Do NOT expose HUMALOG U-100 in the pump reservoir to temperatures greater than 98.6°F (37°C). • Use HUMALOG U-100 in pump systems suitable for insulin infusion [see Patient Counseling Information (17.7)] 2.3 Dosage Information • Individualize and adjust the dosage of HUMALOG based on route of administration, the individual's metabolic needs, blood glucose monitoring results and glycemic control goal. • Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness [see Warnings and Precautions (5.2, 5.3) and Use in Specific Populations (8.6, 8.7)]. • Do NOT perform dose conversion when using either the HUMALOG U-100 or U-200 KwikPens. The dose window shows the number of insulin units to be delivered and no conversion is needed. pi.lilly.com/us/humalog-pen-pi.pdf
AFREZZA • Insulin Naïve Individuals: Start on 4 units of AFREZZA at each meal. • Individuals Using Subcutaneous Mealtime (Prandial) Insulin: Determine the appropriate AFREZZA dose for each meal by converting from the injected dose using Figure 1. Mealtime Dose Adjustment Adjust the dosage of AFREZZA based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal. Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness [see Warnings and Precautions (5.3), and Use in Specific Populations (8.6, 8.7)]. Carefully monitor blood glucose control in patients requiring high doses of AFREZZA. If, in these patients, blood glucose control is not achieved with increased AFREZZA doses, consider use of subcutaneous mealtime insulin.
afrezza.com/wp-content/uploads/2016/08/afrezza.pdf
ssiegel, look at that. The wording is the same. el sameo. heh. Subq package insert does not give titration instructions either.
I remember reading sam was sent home with subq after he was diagnosed. Can you imagine the learning curve, prior to the internet. Anyone that survived that is lucky to be alive. just throwing it out to the atmosphere, learning to dose subq insulin is no picnic. www.slideshare.net/StephenPonder/sugar-surfing-with-a-cgm-copyright-tlc-advanced-diabetes-retreat-april-26-2014
Afrezza on the other hand, picnic.
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Post by mnholdem on May 21, 2017 10:31:32 GMT -5
For illustrative purposes, I think this example is the kind of titration algorithm that ssiegel is referring to: Q1D algorithm1
Using the Q1D algorithm, patients self-titrated every day based on premeal or bedtime blood glucose (BG) readings, respectively, from the previous day. For example, when adjusting the prebreakfast dose, patients used their prelunch readings from the previous day. The premeal target BG was 85-114 mg/dL. If the patient had a BG reading of ≥115 mg/dL, the patient increased the lispro dose by 1 unit/day until the target was reached. For a BG reading of 56-84 mg/dL, the dose was decreased by 1 unit, and for a reading of <56 mg/dL, the dose was decreased by 2 units.
Q3D algorithm1
Using the Q3D algorithm, patients self-titrated every 3 days based on the median (middle) BG readings from the 3 days before.1 Accordingly, to adjust the prebreakfast dose, the patient used the median prelunch BG reading from the past 3 days. If the median reading was 85-114 mg/dL, there was no change in lispro dose. For median 115-144 mg/dL, the patient increased the dose by 2 units. For median ≥145 mg/dL, the dose was increased by 4 units. For median 56-84 mg/dL, the dose was decreased by 2 units. For median <56 mg/dL, the dose was decreased by 4 units.
Source: www.humalog.com/hcp/dosing-self-titration.aspx
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Post by peppy on May 21, 2017 10:43:29 GMT -5
Yes, but that does not instruct how to titrate. It merely tells the patient how to start and that they will need to titrate. The actual act of titration involves adjusting the dose to meet the daily need. That in turn requires measuring the sugar at specific times before and after meals, supplementing, adjusting, etc. Again I refer to figure 1 in the link I provided. The titration guide is under health professional www.afrezza.com/hcp/starting-titrating/ I got an "A" on the test. I bragged about this already.
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