|
Post by mango on Oct 5, 2018 17:19:59 GMT -5
The ADA-EASD Consensus Report was produced by co-chairs John B. Buse, MD, PhD, University of North Carolina School of Medicine, and Melanie J. Davies, MC ChB, MD, University of Leicester, UK; and additional authors David D’Alessio, MD, Duke University, Durham, NC; Judith E. Fradkin, MD, The National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health; Walter N. Kernan, MD, Yale School of Medicine, New Haven, CT; Chantal Mathieu, MD, PhD, Katholieke Universiteit Leuven, Leuven, Belgium; Geltrude Mingrone, MD, PhD, Catholic University of the Sacred Heart, Rome; Peter Rossing, MD, Steno Diabetes Center, Copenhagen; Apostolos Tsapas, MD, PhD, MSc, Artistotle University Thessaloniki, Greece; and Deborah J. Wexler, MD, MSc, Massachusetts General Hospital and Harvard Medical School, Boston. Author disclosures are noted in the manuscript, and the manuscript details the 36 distinguished professionals who served as peer-reviewers. • MannKind Scientific Advisory Board John B. Buse, MD, PhD (Chair, Scientific Advisory Board)www.mannkindcorp.com/about-us/scientific-advisory-board/Time to kick John B. Buse off the SAB? I vote yes.
|
|
|
Post by mnholdem on Oct 5, 2018 17:44:09 GMT -5
Why?
|
|
|
Post by bill on Oct 5, 2018 17:51:32 GMT -5
This is horrible correct? It's either really good or horrible. Really good because MNKD now has a target to beat and knows who the enemy is. If they can prove safety, adherence, and efficacy over GLP-1s, it's going to be an easy road. Really bad because it'll take a lot of work. GLP-1s are known to help with weight loss and cardiac benefits. They're backed by heavy pockets who can afford to design advantageous trials and have greater resources to reach doctors. MNKD has its work cut out for it. Once you have a concept instilled in your mind, it takes a lot of convincing to change perceptions. MNKD may have to prove weight neutrality and cardiac benefit over time and across many different ethnic groups. They may have to prove adherence is higher and leads to better outcomes. They may have to prove the absolute risk ratio is lower with Afrezza vs GLP-1s etc. If you notice, GLP-1s have been on the market for a long time. Afrezza is different enough from other insulins that it may have to pay its dues and wait until the evidence shakes out to prove superiority. Fortunately, this shouldn't take longer than a year or so to flesh out. Adherence will be there only unknown variable at that point, mostly because GLP-1s can be injected every 1-2 weeks. It's a lot easier to adhere to that simplistic of a regimen. stevil - Good grief. Poor MNKD has to convince the world that insulin is better for diabetics than other substances that affect blood glucose, but have a variety of side effects; some good, some not so good? What's so hard for the physicians to understand that insulin is good for all diabetics; as long you can mimic how insulin works for a non-diabetic? Your arguments suggest that MNKD has to prove that the insulin that's not present in PWDs is weight neutral and has a cardiac benefit across ethnic groups? Common sense says that's specious...
|
|
|
Post by agedhippie on Oct 5, 2018 18:11:54 GMT -5
People seem to confuse the role of an advisory board. That role is not to evangelize for the company, it is not to sell the company's products, it is to advise the company. The company is leveraging the advisory board's experience to make decisions faster and smarter. The board members don't even need to like the company's products since they are hired for what they know and their their experience. Selling the product is the job of the company, it's marketing team, and it's salesforce.
Someone is going to ask why they take the job in that case. Having been on a handful of technical advisory boards in my time I can say why I did it. In my case it's because I like being able to contribute to a company's strategic direction. And the money didn't hurt.
|
|
|
Post by bill on Oct 5, 2018 18:20:54 GMT -5
People seem to confuse the role of an advisory board. That role is not to evangelize for the company, it is not to sell the company's products, it is to advise the company. The company is leveraging the advisory board's experience to make decisions faster and smarter. The board members don't even need to like the company's products since they are hired for what they know and their their experience. Selling the product is the job of the company, it's marketing team, and it's salesforce. Someone is going to ask why they take the job in that case. Having been on a handful of technical advisory boards in my time I can say why I did it. In my case it's because I like being able to contribute to a company's strategic direction. And the money didn't hurt. @agedhippe - Agreed, but one WOULD expect an SAB member to ensure that the report authors were AWARE of products and technologies they're familiar with as an SAB member. Creating awareness in other forums would be within the scope of an SAB member wouldn't it?
|
|
|
Post by sayhey24 on Oct 5, 2018 18:23:14 GMT -5
This is horrible correct? It does not endorse Afrezza as the Standard of Care as we are all hoping for. Updating the Standards of Care will be a long process. While I know Dr. Kendall has said its the easiest job he has ever had, its not going to happen over night and the updates will be done in dribs and drabs.
First up will be the T1 standard which on page 73 recommends RAAs to be used to reduce hypos. afrezza is the clear cut winner here. It says "Most individuals with type 1 diabetes should use rapid-acting insulin analogs to reduce hypoglycemia risk."
As a door opener the current standards document is factually wrong on page 80. It currently lists afrezza in the "Rapid Acting Analog" class. This is clearly wrong as afrezza is not an analog. Mike said at Cantor they are working with "Third Parties" for a new class. I expect updates to this document 1Q2019 for the T1 standard.
For the T2s its going to take much longer. Metformin is all over it and we know what Ralph DeFronzo now says about metformin while he use to be its biggest promoter. Now he is promoting GLP-1s and they are a mess.
“The most waste in type 2 diabetes is to continuously put people on metformin and sulfonylureas (glyburide, glimepiride, etc.). These drugs have no protective effect on the beta cell, and by the time you figure out what you’re doing, there are no beta cells left to save.” – Dr. Ralph DeFronzo (University of Texas Health Science Center) diatribe.org/the-diatribe-foundation-and-tcoyd-11th-annual-forum
|
|
|
Post by radgray68 on Oct 5, 2018 19:32:14 GMT -5
Are they seriously saying they put some thought into this? Absolutely nothing new in this report. Still pushing the mostly-ignored lifestyle angle AND PILLS!!! I've said it before and I'll scream it from the rooftops if I have to: When the body needs oxygen, you give it OXYGEN. When the body needs water, you give it WATER. When the body needs insulin, you give it..... everything in the world EXCEPT INSULIN? !! Again, Afrezza, i.e. monomeric insulin, is ignored by the very people who proclaim to be on the forefront of treatment. Downright fraudulent IMHO. I bet Mike could get a California lawyer to argue the case. Hey, get the media on our side and that would be relatively free advertising.
|
|
|
Post by mango on Oct 5, 2018 21:33:55 GMT -5
This is horrible correct? It's either really good or horrible. Really good because MNKD now has a target to beat and knows who the enemy is. If they can prove safety, adherence, and efficacy over GLP-1s, it's going to be an easy road. Really bad because it'll take a lot of work. GLP-1s are known to help with weight loss and cardiac benefits. They're backed by heavy pockets who can afford to design advantageous trials and have greater resources to reach doctors. MNKD has its work cut out for it. Once you have a concept instilled in your mind, it takes a lot of convincing to change perceptions. MNKD may have to prove weight neutrality and cardiac benefit over time and across many different ethnic groups. They may have to prove adherence is higher and leads to better outcomes. They may have to prove the absolute risk ratio is lower with Afrezza vs GLP-1s etc. If you notice, GLP-1s have been on the market for a long time. Afrezza is different enough from other insulins that it may have to pay its dues and wait until the evidence shakes out to prove superiority. Fortunately, this shouldn't take longer than a year or so to flesh out. Adherence will be there only unknown variable at that point, mostly because GLP-1s can be injected every 1-2 weeks. It's a lot easier to adhere to that simplistic of a regimen. Stevil, diabetes is caused from dysregulation in glucose homeostasis. In both T1D and T2D there is loss of the first-phase insulin response. The FPIR is required for maintaining glucose homeostasis. Afrezza is human insulin and physiologically mimics endogenous insulin like that in a healthy, non-diabetic pancreas, and the FPIR with Afrezza is evidenced not only its time to reach the required peak plasma insulin concentrations but also in CGMs. The kinetics of Afrezza allows for successful exogenous replacement of the first-phase insulin response that is absent in the person with diabetes and successful restoration of post-prandial glucose homeostasis. Evidence: Triple pill therapy:Afrezza Therapy
|
|
|
Post by agedhippie on Oct 5, 2018 22:38:11 GMT -5
@agedhippe - Agreed, but one WOULD expect an SAB member to ensure that the report authors were AWARE of products and technologies they're familiar with as an SAB member. Creating awareness in other forums would be within the scope of an SAB member wouldn't it? The SAB member has their hands tied. The ground rules are very clear, the ADA even publishes them. Consensus is data driven and that data has to come from solid large scale trials. That trial data does not exist for Afrezza so the best that can be achieved is equivalence with RAA since it is non-inferior. On the other hand SGLT-2 and GLP-1 have a lot of large trials showing benefit so they make the cut. Really though I would like to see the full statement.
|
|
|
Post by mango on Oct 5, 2018 23:21:52 GMT -5
ADA does not follow the scientific method and 'consensus' has no place in science. There is only two mentions of Afrezza in this new Living SoC update. 1) Page 20: Other Insulin Formulations. Short-and rapid-acting insulin formulations administered at mealtime are generally used to intensify basal insulin therapy in patients not meeting glycemic targets. Options include human regular insulin, various analogs (aspart, glulisine, and lispro), formulations (faster insulin aspart, lispro U200), biosimilars (lispro), and insulins with different routes of administration (inhaled). Rapid-acting insulin analogs have a modestly lower risk for hypoglycemia compared with human regular insulin but at a higher cost. Various premixed formulations of human and analog insulins are available and continue to be widely used in some regions, though they tend to have an increased risk of hypoglycemia as compared with basal insulin alone (Table 2 and Fig. 7). 2) Page 15: Notice they even threw in weight gain under Afrezza disadvantages/adverse effects. Where's the evidence of weight gain with Afrezza? • Corresponding author: John B. Buse, jbuse@med .unc.edu. • M.J.D. and J.B.B. were co-chairs for the Consensus Statement Writing Group. John B. Buse, Chair of MannKind Scientific Advisory Board was also a corresponding author of this document and co-chair for the Consensus Statement Writing Group. I can't find a single cited reference on Afrezza in this Consensus Report. care.diabetesjournals.org/content/diacare/early/2018/09/27/dci18-0033.full.pdf
|
|
|
Post by mango on Oct 6, 2018 2:52:04 GMT -5
@agedhippe - Agreed, but one WOULD expect an SAB member to ensure that the report authors were AWARE of products and technologies they're familiar with as an SAB member. Creating awareness in other forums would be within the scope of an SAB member wouldn't it? The SAB member has their hands tied. The ground rules are very clear, the ADA even publishes them. Consensus is data driven and that data has to come from solid large scale trials. That trial data does not exist for Afrezza so the best that can be achieved is equivalence with RAA since it is non-inferior. On the other hand SGLT-2 and GLP-1 have a lot of large trials showing benefit so they make the cut. Really though I would like to see the full statement. My issue is consensus is an opinion based on feelings and beliefs and a 'scientific consensus' is no different. This Consensus Report even tells us that it is an opinion of the authors. They can also be bias and financially driven. These issues appear to maybe be the case here. • Duality of Interest. M.J.D. reports personal fees and grants from Boehringer Ingelheim, Janssen, Novo Nordisk, and Sanofi and personal fees from AstraZeneca, Eli Lilly, Gilead Sciences Ltd., Intarcia/ Servier, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma Corporation, and Takeda Phar- maceuticals International Inc. D.A.D’A. reports personal fees from Eli Lilly, Merck, Novo Nordisk, and Intarcia and grants from Merck and Ligand during the conduct of the study; personal fees from Eli Lilly, Merck, Novo Nordisk, and Intarcia and grants from Merck and Ligand outside the submitted work. J.F. has nothing to disclose. J.F.’s input into this consensus report is from her own perspective and the report does not reflect the view of the National Institutes of Health, De- partment of Health and Human Services, or the U.S. Government. W.N.K. has nothing to disclose. C.M. reports grants and personal fees from Novo Nordisk, grants and personal fees from Sanofi, grants and personal fees from Merck Sharp & Dohme, grants and personal fees from Eli Lilly and Company, grants and personal fees from Novartis, personal fees from Bristol-Myers Squibb, personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, per- sonal fees from Hanmi Pharmaceuticals, grants and personal fees from Roche Diagnostics, grants and personal fees from Medtronic, grants and personal fees from Intrexon, grants and personal fees from Abbott, and personal fees from UCB, outside the submitted work. G.M. reports grants and personal fees from Novo Nordisk, personal fees from Johnson & Johnson, and personal fees from Fractyl Inc., during the conduct of the study. P.R. reports grants and nonfinancial and other support from Novo Nordisk, grants and other support from AstraZeneca, other support from Bayer, other support from Boehringer Ingelheim, other support from Merck Sharp & Dohme, and other support from Eli Lilly, during the conduct of the study. A.T. reports nonfinancial support from the European Association for the Study of Di- abetes during the conduct of the study; grants and other support from Boehringer Ingelheim, grants and other support from Novo Nordisk, other support from Novartis, grants and other support from Sanofi, grants and other support from AstraZeneca, grants from GSK, and grants and other support from European Foundation for the Study of Diabetes, outside the submitted work. D.J.W. has nothing to disclose. J.B.B. has provided consultation to Adocia, AstraZeneca, Eli Lilly, GI Dynamics, Intarcia, MannKind, NovaTarg, Novo Nordisk, Senseonics, and vTv Therapeutics with fees paid to the University of North Carolina. He has received grant support from AstraZeneca, Johnson & Johnson, Novo Nordisk, Sanofi, and vTv Therapeutics. He is a consultant to Neurimmune AG. He holds stock options in Mellitus Health, PhaseBio, and Stability Health. He is supported by a grant from the National Institutes of Health (UL1TR002489). • Data Sources, Searches, and Study Selection The writing group accepted the 2012 (4) and 2015 (5) editions of this position statement as a starting point. To identify newer evidence, a search was conducted on PubMed for randomized clinical trials (RCTs), systematic reviews, and meta-analyses published in English between 1 January 2014 and 28 February 2018; eligible publications examined the effectiveness or safety of pharmacological or nonpharmacological interventions in adults with type 2 diabetes mellitus. Reference lists were scanned in eligible reports to identify additional articles relevant to the subject. Details on the keywords and the search strategy are available at doi.org/10.17632 h5rcnxpk8w.1. Papers were grouped according to subject, and the authors reviewed this new evidence to inform the consensus recommendations. The draft consensus recommendations were peer reviewed (see “Acknowledgments”), and suggestions incorporated as deemed appropriate by the authors. Nevertheless, though evidence-based, the recommendations presented herein are the opinions of the authors. • Data used in constructing a Scientific Consensus can be derived from using a flawed data gathering design, which appears to be the case here with the search strategy they deployed. Search Strategy• The only hit in their search results related to Afrezza is: Impact of symptomatic upper respiratory tract infections on insulin absorption and action of Technosphere inhaled insulin. Search Results• Relevant Afrezza data that was not included in the Consensus' search results: Systematic reviews and meta-analysis 1. Efficacy, safety, and patient acceptability of Technosphere inhaled insulin for people with diabetes: a systematic review and meta-analysis. www.ncbi.nlm.nih.gov/m/pubmed/26341170/2. Technosphere insulin (Afrezza): a new, inhaled prandial insulin. www.ncbi.nlm.nih.gov/m/pubmed/25313261/3. Future prospect of insulin inhalation for diabetic patients: The case of Afrezza versus Exubera. www.ncbi.nlm.nih.gov/m/pubmed/26222134/Randomized control trials 1. Inhaled Technosphere Insulin Versus Inhaled Technosphere Placebo in Insulin-Naïve Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetes Agents. www.ncbi.nlm.nih.gov/m/pubmed/26253730/Just another day at the ADA.
|
|
|
Post by uvula on Oct 6, 2018 8:01:24 GMT -5
Did Kendall lie to us? If it really is impossible to change the SOC without large scale studies he would have known this.
|
|
|
Post by sayhey24 on Oct 6, 2018 9:13:37 GMT -5
Dr. Kendall is working through the updates. Its a grind and will take years for all the updates which afrezza should have today.
First up is page 80. afrezza is currently in the rapid acting analog class. This is factually wrong so the ADA is compelled to create the new class Mike discussed at Cantor as working with "Third Parties".
Affinity 1 and STAT support changes to page 73 "Most individuals with type 1 diabetes should use rapid-acting insulin analogs to reduce hypoglycemia risk" It should read something like "Most individuals with type 1 diabetes should use inhaled insulin to reduce hypoglycemia risk otherwise rapid acting analog should be used."
|
|
|
Post by agedhippie on Oct 6, 2018 9:26:31 GMT -5
Did Kendall lie to us? If it really is impossible to change the SOC without large scale studies he would have known this. He didn't lie. He can get the standard of care changed, just not in the way that people had been thinking. There is an expectation that Afrezza will recommended over all other treatments for Type 1, and moved up to be the first line treatment displacing metformin, GLP-1 SGLT-2, DPP-4, etc. Achieving those aims will take both time and large scale trials because it would be a huge change, I think you are talking years. What he can do is make sure that Afrezza is mentioned alongside RAA in the Standard of Care when there are treatments laid out. Afrezza has the data to support that non-inferior rating so if they talk about injectables they should also talk about inhaled insulin.
|
|
|
Post by agedhippie on Oct 6, 2018 9:47:37 GMT -5
ADA does not follow the scientific method and 'consensus' has no place in science. The ADA follow an evidence based approach and they lay out their methodology very clearly at the start of the Standard of Care. Until the rules are changed those are the rules everyone is playing under whether people like it or not. Are they the best, cleverest, smartest, whatever, rules? Probably not, but the thing is they are the rules so that's where we are.
|
|