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Post by joeypotsandpans on Sept 3, 2017 14:03:46 GMT -5
Both would be nice, however, I believe only "ultra-rapid" would put Afrezza in a separate category. The label change should be as simple as categorizing it as Monomeric Insulin, and separating it from Hexameric Insulin, that in and of itself would distinguish it from the other current RAA's. See below (source: www.ebi.ac.uk/pdbe/widgets/QuipStories/insulin/insulin.pdf ) A spoonful of sugar helps the medicine go down... ..." But not if the medicine is insulin as this is administered by injection under the skin! With this
method, the rapid dilution of zinc and the pH change that take place when insulin is secreted
by the pancreas do not occur and stable hexamers remain, which leads to suboptimal drug
delivery. With the advent of recombinant technology, modified forms of insulin have been produced which are better suited as drugs compared to the wildtype human protein. A form in which residue 28 at the C-terminal end of the B chain is mutated from proline to aspartate (insulin aspart - NovoRapid) (PDB entries 1zeg, 1zeh or 1kei) (view-4) displays greater flexibility in the C-terminal region, disrupting the assembly of the insulin dimer and favouring the monomeric form. This leads to a more rapid transfer of the molecule from the subcutaneous injection site into the bloodstream. Similarly, the drug Humalog (PDB entries 1lph or 2kjj) (view- 4), sold by Eli Lily, has two amino acids swapped at the C- terminus of the B chain (Pro28 and Lys29 are changed to Lys28 and Pro29). This change also favours the monomeric form
whilst not affecting the activity of the hormone. In both cases, the hexameric form prevails in the presence of zinc and the high concentrations used for crystallization and drug storage, but
compared to wildtype insulin, monomerisation is much more rapid in vivo."
so forget about the fast, rapid, ultra-rapid....just classify as Monomeric and it would stand on the shelf by itself, that makes the most sense as it can't be touched or have to share the space with the others and would finally get it's due with the features and advantages of monomeric insulin and what Al knew since day 1.  |
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Post by Deleted on Sept 3, 2017 14:07:25 GMT -5
I believe the reduced probability of hypoglycemia is due to the quickness of elimination; outsulin. Did MannKind submit data for reduced hypoglycemia?
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Post by lennymnkd on Sept 3, 2017 14:35:55 GMT -5
Both would be nice, however, I believe only "ultra-rapid" would put Afrezza in a separate category. The label change should be as simple as categorizing it as Monomeric Insulin, and separating it from Hexameric Insulin, that in and of itself would distinguish it from the other current RAA's. See below (source: www.ebi.ac.uk/pdbe/widgets/QuipStories/insulin/insulin.pdf ) A spoonful of sugar helps the medicine go down... ..." But not if the medicine is insulin as this is administered by injection under the skin! With this
method, the rapid dilution of zinc and the pH change that take place when insulin is secreted
by the pancreas do not occur and stable hexamers remain, which leads to suboptimal drug
delivery. With the advent of recombinant technology, modified forms of insulin have been produced which are better suited as drugs compared to the wildtype human protein. A form in which residue 28 at the C-terminal end of the B chain is mutated from proline to aspartate (insulin aspart - NovoRapid) (PDB entries 1zeg, 1zeh or 1kei) (view-4) displays greater flexibility in the C-terminal region, disrupting the assembly of the insulin dimer and favouring the monomeric form. This leads to a more rapid transfer of the molecule from the subcutaneous injection site into the bloodstream. Similarly, the drug Humalog (PDB entries 1lph or 2kjj) (view- 4), sold by Eli Lily, has two amino acids swapped at the C- terminus of the B chain (Pro28 and Lys29 are changed to Lys28 and Pro29). This change also favours the monomeric form
whilst not affecting the activity of the hormone. In both cases, the hexameric form prevails in the presence of zinc and the high concentrations used for crystallization and drug storage, but
compared to wildtype insulin, monomerisation is much more rapid in vivo."
so forget about the fast, rapid, ultra-rapid....just classify as Monomeric and it would stand on the shelf by itself, that makes the most sense as it can't be touched or have to share the space with the others and would finally get it's due with the features and advantages of monomeric insulin and what Al knew since day 1. Now why didn't I think of that ! 😀👍 |
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Post by peppy on Sept 3, 2017 14:50:25 GMT -5
I believe the reduced probability of hypoglycemia is due to the quickness of elimination; outsulin. Did MannKind submit data for reduced hypoglycemia? So let me move on from our Afrezza clinical program and just touch upon the submitted label revision. As I've done in the past, I've shown that these are the graphs that we are submitted and to the FDA for a label change and it really demonstrates our Afrezza's unique PKPD profile. You clearly see in the upper right-hand graph, the much earlier onset versus the Lispro versus Afrezza. You also see a much rapid return to baseline with Afrezza versus Lispro.
First the label change has a couple aspects to it and I think about it in three steps one there is the ability to articulate that the drug starts working within five minutes. The second part is we can articulate that it is faster than the competition. And the third is asking for a different category altogether. The important of these commercially really vary in terms of impact now in the second half of 2017 but as we go in 2018 and beyond.
As repute to communicate we expect PDUFA approval by the end of Q3. So this will be a Q4 event in terms of launch and impact. Depending on which combination of those three activities happen really will depend on the upside in terms of the forecast and the accelerate growth that we expect post the label change.
So for example if we were to get a different category that opens up a lot of the managed care access, if we takes that out of the bucket that we’re currently restricted in by the competition. So we don’t always control the buckets they’re consumed by the PBMs that drive 70% of the units in the country that really opens that window a little bit. It also dramatically could change Medicare Part D coverage.
When it comes to the speed of onset saying we work within five minutes the reason that's important as we’re running these trials right now with DexCom and what you can see is within three dots on the DexCom you can see whether you got your appropriate dose we need to follow up the dose. Being able to have the clinical data that we kicked off coming out in time frame and read for us internally to know what the label change is going to be we are waiting to see a couple dots on their CGM which way did overshoot or undershoot for dosing in order to pull them back into time and range very quickly.
We expect that the five minutes claim to be in there the data supports that and something we’re excited about. The other thing I can tell you is when we shared that PK/PD curve with the physician and asked them what does this mean to you the five-minute onset meant more to the physician than we expected in terms of just understanding the PK/PD is a product the speed of onset, getting out of body fast and all the things that come without backing of insulin and injecting. So that really gave them some confidence around how to mince with a drug and what they can communicate to the patient's.
And then getting out of body faster and we know to make that claim is read our label today we say we get in the body faster, but we can't necessarily say we work any faster. And that’s been something that’s been bothering us since launch. And this to me is a very important label update is it really will allow to finally articulate the true profile of this product at least from the PK/PD. When you take that label change plus the work that Ray has been doing and his team that we’re really working on this one-two punch combination and when it comes to some of these things. I hope that answer your question Jason.
seekingalpha.com/article/4096149-mannkinds-mnkd-ceo-michael-castagna-q2-2017-results-earnings-call-transcript?part=single
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Post by mango on Sept 3, 2017 14:52:17 GMT -5
I believe the reduced probability of hypoglycemia is due to the quickness of elimination; outsulin. Did MannKind submit data for reduced hypoglycemia? Early phase insulin response—Afrezza reaches peak serum levels in the amount of time required to mimic this physiologically. It introduces to the body a large rush and rapid rate of change in insulin concentration which suppresses the production of glucagon and reduces hepatic glucose excretion. The short, rapid rise in peak serum insulin concentration is required for rapidly suppressing endogenous glucose production and this also will compress the action of insulin to the peri-prandial time interval. |
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Post by agedhippie on Sept 3, 2017 16:40:07 GMT -5
I believe the reduced probability of hypoglycemia is due to the quickness of elimination; outsulin. Did MannKind submit data for reduced hypoglycemia? The data was collected in both the T1 and T2 trials. The results for the T1 trials were good, the results for the T2 trials were not since it was competing against drugs that seldom cause hypos. I think the label change would have to be for T1 alone but I would take that in a heartbeat since it's where the market is today. The bottom line is that for T1 Afrezza shows clear superiority over RAA in hypo reduction. That is exactly the sort of thing that will get a drug prescribed - a doctor needs to know the treatment benefit of prescribing option A over option B and this is a rock solid benefit. |
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Post by mango on Sept 3, 2017 16:55:31 GMT -5
I believe the reduced probability of hypoglycemia is due to the quickness of elimination; outsulin. Did MannKind submit data for reduced hypoglycemia? The data was collected in both the T1 and T2 trials. The results for the T1 trials were good, the results for the T2 trials were not since it was competing against drugs that seldom cause hypos. I think the label change would have to be for T1 alone but I would take that in a heartbeat since it's where the market is today. The bottom line is that for T1 Afrezza shows clear superiority over RAA in hypo reduction. That is exactly the sort of thing that will get a drug prescribed - a doctor needs to know the treatment benefit of prescribing option A over option B and this is a rock solid benefit. In the 24 week open label Phase 3 clinical trial— • TI alone or in combination with metformin was well-tolerated over 24 weeks of treatment. FIGs. 17- 28 depict the results of the study. The safety profile of TI was similar to that observed in earlier trials in the TI clinical development program; no safety signals emerged over the course of the trial. Very low rates of severe hypoglycemia were observed in all treatment groups with no cases occurring in patients treated with TI alone or with oral hypoglycemics and in 2% of patients when TI and metformin were combined. Even with such marked reductions in HbA1c overall, no increases in weight were seen. Detailed assessment of pulmonary safety including FEv1 and DLCO over the 24 weeks of the study showed no difference in pulmonary function between patients inhaling TI and those on oral therapy alone.TI + Metformin• TI + metformin provided statistically superior postprandial control compared to metformin + secretagogue after 12 and 24 weeks of treatment and a comparable mean reduction from baseline in FPG after 24 weeks. There was mean weight loss (-0.75 kg) over 24 weeks in this treatment group and an overall incidence of mild-to-moderate hypoglycemia of 35.0%.TI Alone• For those subjects that completed the trial, prandial TI alone was successful in providing a clinically significant mean reduction from baseline in HbA1c (1.82 [1.1] %) after 24 weeks of treatment. The change from baseline was numerically superior to the standard anti-hyperglycemic regimen of metformin + secretagogue. At trial endpoint, TI alone provided significantly more effective postprandial control than comparator with a comparable mean reduction from baseline in FPG. There was net weight loss (-0.04 kg) over 24 weeks in this treatment group and an overall incidence of mild-to-moderate hypoglycemia of 27.6%.These data show that Afrezza is superior to Metformin. |
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Post by stew3409 on Sept 3, 2017 17:30:31 GMT -5
mango that just shows TI when used with metformin has higher rate of hypo and that docs be aware of that. It doesn't mean metforfmin is superior to TI based on the data presented. If you had worked at FDA TI could have gotten the label that it cured diabetes 😜
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Post by mango on Sept 3, 2017 19:03:17 GMT -5
mango that just shows TI when used with metformin has higher rate of hypo and that docs be aware of that. It doesn't mean metforfmin is superior to TI based on the data presented. If you had worked at FDA TI could have gotten the label that it cured diabetes 😜 It shows that when TI + Metformin is used, hypo rates increase. But when given TI alone, hypo rates decrease. The data shows TI is superior to Metformin and even Metformin + other pills |
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Post by stew3409 on Sept 3, 2017 20:47:53 GMT -5
mango that just shows TI when used with metformin has higher rate of hypo and that docs be aware of that. It doesn't mean metforfmin is superior to TI based on the data presented. If you had worked at FDA TI could have gotten the label that it cured diabetes 😜 It shows that when TI + Metformin is used, hypo rates increase. But when given TI alone, hypo rates decrease. The data shows TI is superior to Metformin and even Metformin + other pills Humalog plus novolog gives higher rate of hypo Humalog only gives lesser incidents of hypo Humalog is superior I like your logic. |
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Post by rockstarrick on Sept 3, 2017 21:29:52 GMT -5
It shows that when TI + Metformin is used, hypo rates increase. But when given TI alone, hypo rates decrease. The data shows TI is superior to Metformin and even Metformin + other pills Humalog plus novolog gives higher rate of hypo Humalog only gives lesser incidents of hypo Humalog is superior I like your logic. You must be really new 😂😂 pick your battles carefully !! my money is on Mango. Good Luck 🇺🇸 |
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Post by mango on Sept 3, 2017 23:34:44 GMT -5
It shows that when TI + Metformin is used, hypo rates increase. But when given TI alone, hypo rates decrease. The data shows TI is superior to Metformin and even Metformin + other pills Humalog plus novolog gives higher rate of hypo Humalog only gives lesser incidents of hypo Humalog is superior I like your logic. 1) • Afrezza is diabadass insulin. • Metformin is not insulin. 2) • Lispro and aspart are both insulins. • Lispro and aspart are both RAAs. 3) • Participants that used Afrezza + Metformin resulted in more hypo events compared to participants that only used Afrezza. • Participants that used Afrezza alone, without Metformin, resulted in significantly less hypos. 4) • Metformin in combination with Afrezza increases the risk of hypoglycemia. • Afrezza, the diabadass insulin, does not have a risk for severe hypoglycemia. Consensus: Afrezza restores and maintains glucose homeostasis. |
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Post by agedhippie on Sept 4, 2017 10:19:05 GMT -5
The data was collected in both the T1 and T2 trials. The results for the T1 trials were good, the results for the T2 trials were not since it was competing against drugs that seldom cause hypos. I think the label change would have to be for T1 alone but I would take that in a heartbeat since it's where the market is today. The bottom line is that for T1 Afrezza shows clear superiority over RAA in hypo reduction. That is exactly the sort of thing that will get a drug prescribed - a doctor needs to know the treatment benefit of prescribing option A over option B and this is a rock solid benefit. In the 24 week open label Phase 3 clinical trial— • TI alone or in combination with metformin was well-tolerated over 24 weeks of treatment. FIGs. 17- 28 depict the results of the study. The safety profile of TI was similar to that observed in earlier trials in the TI clinical development program; no safety signals emerged over the course of the trial. Very low rates of severe hypoglycemia were observed in all treatment groups with no cases occurring in patients treated with TI alone or with oral hypoglycemics and in 2% of patients when TI and metformin were combined. Even with such marked reductions in HbA1c overall, no increases in weight were seen. Detailed assessment of pulmonary safety including FEv1 and DLCO over the 24 weeks of the study showed no difference in pulmonary function between patients inhaling TI and those on oral therapy alone.TI + Metformin• TI + metformin provided statistically superior postprandial control compared to metformin + secretagogue after 12 and 24 weeks of treatment and a comparable mean reduction from baseline in FPG after 24 weeks. There was mean weight loss (-0.75 kg) over 24 weeks in this treatment group and an overall incidence of mild-to-moderate hypoglycemia of 35.0%.TI Alone• For those subjects that completed the trial, prandial TI alone was successful in providing a clinically significant mean reduction from baseline in HbA1c (1.82 [1.1] %) after 24 weeks of treatment. The change from baseline was numerically superior to the standard anti-hyperglycemic regimen of metformin + secretagogue. At trial endpoint, TI alone provided significantly more effective postprandial control than comparator with a comparable mean reduction from baseline in FPG. There was net weight loss (-0.04 kg) over 24 weeks in this treatment group and an overall incidence of mild-to-moderate hypoglycemia of 27.6%.These data show that Afrezza is superior to Metformin. All of that is from a patent filing. Do you have a link to the trials mentioned? It's an old patent and uses Medtone inhalers rather than Dreamboat, and was superseded by the 175 study which was used in the ADCOM. I am curious as to what they were doing about basal, etc. on the TI only arm. |
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Post by rockstarrick on Sept 4, 2017 17:40:29 GMT -5
You must be really new 😂😂 pick your battles carefully !! my money is on Mango. Good Luck 🇺🇸 Yes by stating irrelevant facts? Ok I got you and I choose to mute myself Just having a little fun stew, nothing personal Welcome 🇺🇸 |
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Post by mango on Sept 4, 2017 18:51:31 GMT -5
mango u r drifting away from the point. I am not comparing metformin with Afrezza or raa with Afrezza. You don't have to preach to the choir. The study results tells everyone to be careful to watch out for hypos when some one is on metformin and starting on Afrezza or vice versa. Combination has given higher incidence of hypos. By stating hematosis, superiority doesn't change the above study results. The doctor should still be cautious. I think I made myself clear and can't make it any more clearer I never drifted from any point, you tried to troll a non-sensical analogy and it didn't work. Yes, you're as clear as miso soup. |
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