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Post by peppy on Apr 29, 2018 9:48:34 GMT -5
ilovekauai , Denise, you know Joey and now Winston are saying afrezza/libre. I think it would be sweet to know what is happening CGM. I wish the world had non invasive.
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Post by agedhippie on Apr 29, 2018 10:46:43 GMT -5
Please review "agehippie"'s comment about six posts ago and if you don't believe him, email Mannkind and ask them. Digger - OK I reviewed Aged's comments. What I can say is you guys make me dizzy going in cirlce's. Simple question - Where did the requirement for spirometry come from? If I remember correctly from the days of the Adcom it was part of the risk mitigation strategy, aka the REMS. Simple question 2 - If the REMS is gone, we know the communication plan also gone but is the requirement for spirometry gone too? It sure seems so. Trimmed it down to just the questions. Answer 1: The requirement for spiro comes from the label which is FDA document. The basis for inclusion in the label is the Summary Review document. Answer 2: You are conflating two unrelated requirements; the requirement to tell doctors the risk exists (the REMS), and the requirement to ensure that the patient is a suitable candidate for Technosphere (the spiro). From the FDA Summary Review document that consolidates all the review and justifies both approval and the label: In patients with chronic underlying lung disease the risk of serious bronchospasm outweighs any potential benefits of Afrezza and in these patients the drug will be contraindicated. It is clear that the serious risk of acute bronchospasm can be prevented by appropriate patient selection. A Boxed Warning will be used to: describe the serious risk, the population for whom the drug is contraindicated and measures that prescribers should follow to prevent occurrence of this serious risk (i.e., appropriate patient selection). A risk evaluation and mitigation strategy (REMS) which includes a communication plan to inform prescribers about this risk will be implemented.The goals of the REMS is defined in the subsequent REMS letter from the FDA and restricted to just communication of risk. The spiro is required for " appropriate patient selection".
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Post by nadathing on Apr 29, 2018 11:02:09 GMT -5
I just sent Mike an email about my experience at Park Nicollet and asked if they had called on the International Diabetes Center. I'll post his reply if I get one.
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Post by sayhey24 on Apr 29, 2018 19:03:51 GMT -5
Digger - OK I reviewed Aged's comments. What I can say is you guys make me dizzy going in cirlce's. Simple question - Where did the requirement for spirometry come from? If I remember correctly from the days of the Adcom it was part of the risk mitigation strategy, aka the REMS. Simple question 2 - If the REMS is gone, we know the communication plan also gone but is the requirement for spirometry gone too? It sure seems so. Trimmed it down to just the questions. Answer 1: The requirement for spiro comes from the label which is FDA document. The basis for inclusion in the label is the Summary Review document. Answer 2: You are conflating two unrelated requirements; the requirement to tell doctors the risk exists (the REMS), and the requirement to ensure that the patient is a suitable candidate for Technosphere (the spiro). From the FDA Summary Review document that consolidates all the review and justifies both approval and the label: In patients with chronic underlying lung disease the risk of serious bronchospasm outweighs any potential benefits of Afrezza and in these patients the drug will be contraindicated. It is clear that the serious risk of acute bronchospasm can be prevented by appropriate patient selection. A Boxed Warning will be used to: describe the serious risk, the population for whom the drug is contraindicated and measures that prescribers should follow to prevent occurrence of this serious risk (i.e., appropriate patient selection). A risk evaluation and mitigation strategy (REMS) which includes a communication plan to inform prescribers about this risk will be implemented.The goals of the REMS is defined in the subsequent REMS letter from the FDA and restricted to just communication of risk. The spiro is required for " appropriate patient selection". Aged - thanks but I think its best if we wait and see where this goes. Here is the definition of the REMS from the REMS document A REMS (RISK Evaluation and Mitigation Strategy) is a program required by the FDA to manage known or potential serious risks associated with a drug product. FDA has determined that a REMS is necessary to ensure that the benefits of Afrezza outweigh the risks of acute bronchospasm in patients.In your above paragraph from 2014 it says "the risk of serious bronchospasm outweighs any potential benefits", as stated above this was the basis for the REMS. In the 4/24 letter it say "We have determined that the communication plan is no longer necessary as an element of the REMS to ensure the benefits of Afrezza (insulin human) inhalation powder outweigh its risks" and then goes on and says " a REMS is no longer required for Afrezza". If a REMS is no longer required then I think we can agree the FDA must have determined the benefits of afrezza DO outweigh the risks of acute bronchospasm in patients. How they made that determination is still a mystery to me. Was it Mike's cologne? Additionally your answer 1 says spirometry is required because its on the label. This is absolutely correct today since the label has not yet changed and will require another sNDA. However the reason it is on the label was to mitigate risk as part of the REMS for "appropriate patient selection". Remember what you included above, the 2014 position was "the risk of serious bronchospasm outweighs any potential benefits of Afrezza" The 2018 position is the "benefits of Afrezza (insulin human) inhalation powder outweigh its risks". I think we can all agree the REMS is now gone per the 4/24 letter. I think we can also agree that a spirometry is not required to use afrezza and it was not part of the 171 and 175 studies and MNKD would not have asked the FDA to include it on the label but rather the FDA required it. In fact, Sanofi blamed the spirometry requirement for lack of sales at the 2015 ASM.
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Post by digger on Apr 29, 2018 20:24:34 GMT -5
Trimmed it down to just the questions. Answer 1: The requirement for spiro comes from the label which is FDA document. The basis for inclusion in the label is the Summary Review document. Answer 2: You are conflating two unrelated requirements; the requirement to tell doctors the risk exists (the REMS), and the requirement to ensure that the patient is a suitable candidate for Technosphere (the spiro). From the FDA Summary Review document that consolidates all the review and justifies both approval and the label: In patients with chronic underlying lung disease the risk of serious bronchospasm outweighs any potential benefits of Afrezza and in these patients the drug will be contraindicated. It is clear that the serious risk of acute bronchospasm can be prevented by appropriate patient selection. A Boxed Warning will be used to: describe the serious risk, the population for whom the drug is contraindicated and measures that prescribers should follow to prevent occurrence of this serious risk (i.e., appropriate patient selection). A risk evaluation and mitigation strategy (REMS) which includes a communication plan to inform prescribers about this risk will be implemented.The goals of the REMS is defined in the subsequent REMS letter from the FDA and restricted to just communication of risk. The spiro is required for " appropriate patient selection". Aged - thanks but I think its best if we wait and see where this goes. Here is the definition of the REMS from the REMS document A REMS (RISK Evaluation and Mitigation Strategy) is a program required by the FDA to manage known or potential serious risks associated with a drug product. FDA has determined that a REMS is necessary to ensure that the benefits of Afrezza outweigh the risks of acute bronchospasm in patients.In your above paragraph from 2014 it says "the risk of serious bronchospasm outweighs any potential benefits", as stated above this was the basis for the REMS. In the 4/24 letter it say "We have determined that the communication plan is no longer necessary as an element of the REMS to ensure the benefits of Afrezza (insulin human) inhalation powder outweigh its risks" and then goes on and says " a REMS is no longer required for Afrezza". If a REMS is no longer required then I think we can agree the FDA must have determined the benefits of afrezza DO outweigh the risks of acute bronchospasm in patients. How they made that determination is still a mystery to me. Was it Mike's cologne? Additionally your answer 1 says spirometry is required because its on the label. This is absolutely correct today since the label has not yet changed and will require another sNDA. However the reason it is on the label was to mitigate risk as part of the REMS for "appropriate patient selection". Remember what you included above, the 2014 position was "the risk of serious bronchospasm outweighs any potential benefits of Afrezza" The 2018 position is the "benefits of Afrezza (insulin human) inhalation powder outweigh its risks". I think we can all agree the REMS is now gone per the 4/24 letter. I think we can also agree that a spirometry is not required to use afrezza and it was not part of the 171 and 175 studies and MNKD would not have asked the FDA to include it on the label but rather the FDA required it. In fact, Sanofi blamed the spirometry requirement for lack of sales at the 2015 ASM. Yes, "we have determined that the communication plan is no longer necessary as an element of the REMS..." and this was the communication plan: 1. REMS letters -- "MannKind Corporation will send a REMS Letter for Healthcare Providers and REMS Letter for Professional Societies within 60 days of this REMS approval (June 2014) and again after one year from the date of the REMS approval. " 2. A REMS fact sheet that was to be distributed to healthcare providers for 18 months after the approval. 3. A REMS website 4. Dissemination of REMS information at scientific meetings Mannkind was also supposed to submit REMS assessments at 18 monthss, 3 years, and 7 years after the initial REMS approval. And all of that no longer needs to be done. There was no change in the black box, warnings, or anything else on the label. If you wish, email Mannkind and/or tweet Mike C. to confirm.
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Post by peppy on May 6, 2018 5:25:58 GMT -5
NADATHING You really should contact Mannkind and ask them to contact your clinic. If the clinic won't see a rep (many don't) Mike or someone on the executive team can contact them. They can't hide from information about new drugs their patients want or could benefit from and call themselves a "Diabetes Center". Park Nicollet is one of the largest health care systems in MN. I would have to believe that their systems allows pharma reps to access their people at some level, but they do not have direct access to doctors. I had a nurse instruct me on how to use Trulicity and I also asked her if she was aware of Afrezza and she was. She told me she knew of one patient on Afrezza that had experienced good results. That patient was being treated by a physician who practiced general medicine. How that physician or department became aware of Afrezza is unknown to me. Just for kicks, I will email Mike and tell him of my experience and see if I get a response. My A1c is 5.8. That is another factor. I can't imagine a doctor prescribing Afrezza when a T2 has tight control using existing treatment. I knows that Afrezza acts differently and the benefits. Changing the way docs treat diabetes is a slow and arduous process. David Kendall Native of Minneapolis and St. Peter, Minnesota – St. Olaf College – University of Minnesota Medical School Assistant – Associate Professor of Medicine – Univ. of Minnesota International Diabetes Center (Minneapolis, MN) – Medical Director and Chief of Clinical Services Amylin Pharmaceuticals – Executive Medical Director American Diabetes Association – Chief Scientific & Medical Officer Lilly Diabetes (Eli Lilly & Co) – VP Global Medical Affairs and Distinguished Medical Fellow People on this board screaming for years, the blackbox on afrezza for bronchospasm was hurting afrezza sales. The black box on trulicity, seems more serious. Eli Lilly has the money to get past this. WARNING: RISK OF THYROID C-CELL TUMORS See full prescribing information for complete boxed warning. • Dulaglutide causes thyroid C-cell tumors in rats. It is unknown whether TRULICITY causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined (5.1, 13.1). • TRULICITY is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors (4, 5.1). So physicians do not want to prescribe medication that may cause a bronchospasm; however, a medication that causes thyroid cancer is prescribed. What is wrong with this picture? Eli Lilly got Trulicity approved for insurance? The criteria is HbA1c? so if HbA1c comes down, thyroid cancer in mice is ok? • Administer once weekly at any time of day (2.1). • Inject subcutaneously in the abdomen, thigh, or upper arm (2.1). • Initiate at 0.75 mg subcutaneously once weekly. Dose can be increased to 1.5 mg once weekly for additional glycemic control (2.1). 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action TRULICITY contains dulaglutide, which is a human GLP-1 receptor agonist with 90% amino acid sequence homology to endogenous human GLP-1 (7-37). Dulaglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase in pancreatic beta cells. Dulaglutide increases intracellular cyclic AMP (cAMP) in beta cells leading to glucose-dependent insulin release. Dulaglutide also decreases glucagon secretion and slows gastric emptying.
Decreases glucagon secretion. LIVER. So Trulicity, pancreas, liver, intestinal tract. hmmmm.
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Post by sayhey24 on May 6, 2018 5:50:52 GMT -5
While back on the subject here is a nice overview on what a REMS is. www.fda.gov/downloads/AboutFDA/Transparency/Basics/UCM328784.pdfThe spirometry would fall under the REMS category Elements To Assure Safe Use (ETASU). ETASU requirements are intended to reduce a specific serious risk listed in the labeling of the drug. A good example similar to afrezza's spirometry is Letairis(ambrisentan), a drug used to treat high blood pressure in the lungs: Removed requirement for liver function testing.
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Post by digger on May 6, 2018 20:36:48 GMT -5
While back on the subject here is a nice overview on what a REMS is. www.fda.gov/downloads/AboutFDA/Transparency/Basics/UCM328784.pdfThe spirometry would fall under the REMS category Elements To Assure Safe Use (ETASU). ETASU requirements are intended to reduce a specific serious risk listed in the labeling of the drug. A good example similar to afrezza's spirometry is Letairis(ambrisentan), a drug used to treat high blood pressure in the lungs: Removed requirement for liver function testing. Yes, but that was because other trials and post-marketing studies determined that the elevated liver enzymes could be explained by other concurrent ailments such as CHF. Afrezza, however, can't collect post-marketing data for COPD patients since it is contraindicated in those patients by mannkind's own request. Similarly, having excluded those patients, no one can do trials to assess the effects of afrezza. And because the spirometry is part of the assessment to rule out pre-existing lung disease, there's little if anything that can be done to remove it.
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Post by mnholdem on May 6, 2018 21:05:30 GMT -5
Actually, digger , the detailed medical history and physical examination could easily rule out pre-existing lung disease. The FEV1 requirement goes way beyond that. Like I said in a separate post, the Afrezza label also says that it should not be prescribed to pregnant women. Should the doctor also be required to perform a pregnancy test just to make sure the female patient isn't pregnant? Your statement that there's "nothing that can be done" is pure assumption and not logically sound.
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Post by agedhippie on May 6, 2018 21:32:03 GMT -5
Actually, digger , the detailed medical history and physical examination could easily rule out pre-existing lung disease. The FEV1 requirement goes way beyond that. Like I said in a separate post, the Afrezza label also says that it should not be prescribed to pregnant women. Should the doctor also be required to perform a pregnancy test just to make sure the female patient isn't pregnant? Your statement that there's "nothing that can be done" is pure assumption and not logically sound.
The FEV-1 requirement is to monitor for a decrease in lung function. The FDA did not require an FEV-1 test to identify undiagnosed lung disease, the review says no consensus was reached which means the responsibility to detect any lung disease falls on the doctor and how that is achieved is the doctor's decision provided it is competently done.
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Post by mnholdem on May 6, 2018 22:09:10 GMT -5
Actually, digger , the detailed medical history and physical examination could easily rule out pre-existing lung disease. The FEV1 requirement goes way beyond that. Like I said in a separate post, the Afrezza label also says that it should not be prescribed to pregnant women. Should the doctor also be required to perform a pregnancy test just to make sure the female patient isn't pregnant? Your statement that there's "nothing that can be done" is pure assumption and not logically sound.
The FEV-1 requirement is to monitor for a decrease in lung function. The FDA did not require an FEV-1 test to identify undiagnosed lung disease, the review says no consensus was reached which means the responsibility to detect any lung disease falls on the doctor and how that is achieved is the doctor's decision provided it is competently done. So, then, the wording of FDA's black box warning should be changed? --- WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE
- Acute bronchospasm has been observed in patients with asthma and COPD using AFREZZA.
- AFREZZA is contraindicated in patients with chronic lung disease such as asthma or COPD.
- Before initiating AFREZZA, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.
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Post by digger on May 6, 2018 22:34:52 GMT -5
Actually, digger , the detailed medical history and physical examination could easily rule out pre-existing lung disease. The FEV1 requirement goes way beyond that. Like I said in a separate post, the Afrezza label also says that it should not be prescribed to pregnant women. Should the doctor also be required to perform a pregnancy test just to make sure the female patient isn't pregnant? Your statement that there's "nothing that can be done" is pure assumption and not logically sound.
The FEV-1 requirement is to monitor for a decrease in lung function. The FDA did not require an FEV-1 test to identify undiagnosed lung disease, the review says no consensus was reached which means the responsibility to detect any lung disease falls on the doctor and how that is achieved is the doctor's decision provided it is competently done. As pointed out previously, the way I read it, the FDA didn't require anything. It was Mannkind: "However, Mannkind has proposed in the Afrezza labeling that Afrezza be contraindicated in patients with a current diagnosis or history of asthma, chronic obstructive pulmonary disease (COPD) or other chronic lung disease. The sponsor also has proposed labeling under Warnings and Precautions that Afrezza not be recommended for current smokers and those who have smoked in the last 6 months and that prior to initiating therapy with Afrezza, all patients should be clinically evaluated with a detailed medical history, physical examination and spirometry (FEV1) to identify any potential underlying disease." Note the way it is phased: "detailed medical history, physical examination and spirometry (FEV1)" should be done "to identify any potential underlying disease." That's what they requested because of what they -- Mannkind themselves -- saw in the trial. There is no "taksies backsies" at this point. Having determined that using afrezza in a COPDer presents some sort of serious risk, they're pretty much stuck with making sure someone doesn't have lung disease before starting afrezza.
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Post by mnholdem on May 6, 2018 22:52:44 GMT -5
Is "no taksies backsies" found somewhere in the FDA regs? It's quite volumous, so I may have missed it. Also, if I recall correctly, CEO Michael Castagna made comments, shortly after being promoted by the BoD, that past management made a real mess of Afrezza [paraphrased] and that the current management team was working to rectify past mistakes.
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Post by digger on May 7, 2018 7:12:53 GMT -5
Is "no taksies backsies" found somewhere in the FDA regs? It's quite volumous, so I may have missed it. Also, if I recall correctly, CEO Michael Castagna made comments, shortly after being promoted by the BoD, that past management made a real mess of Afrezza [paraphrased] and that the current management team was working to rectify past mistakes. Have they said anything about trying to get the black box changed? Again, I don't see how Mannkind can since they effectively proved that there was some serious risk to people with COPD attempting to use afrezza. What would you or they do to change that?
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Post by peppy on May 7, 2018 7:24:10 GMT -5
Is "no taksies backsies" found somewhere in the FDA regs? It's quite volumous, so I may have missed it. Also, if I recall correctly, CEO Michael Castagna made comments, shortly after being promoted by the BoD, that past management made a real mess of Afrezza [paraphrased] and that the current management team was working to rectify past mistakes. Have they said anything about trying to get the black box changed? Again, I don't see how Mannkind can since they effectively proved that there was some serious risk to people with COPD attempting to use afrezza. What would you or they do to change that? MNKD does not need to change that. RAA's are old and lousy. The people with COPD need to use old and lousy. As far as black box labels, GLP-1 thyroid cancer. SGLT2 amputation, although less heart attacks heh. RAA hyperglycemia and hypoglycemia, Dr. Kevorkian. Heart Attack.
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