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Post by mnholdem on Nov 6, 2015 14:21:32 GMT -5
I think this study is significant. Like many others I have wondered why is Sanofi going so slowly with Afrezza? I have had my doubts about their commitment, even after the investor presentation today. One of my hypotheses is that Sanofi doesn't want to bury Mannkind under a load of research and marketing costs given the nature of their agreement. If they did that before enough sales develop, they could bankrupt their smaller partner easily. This is a Praluent study. Brandicourt thinks it has blockbuster potential. So why would Afrezza and Lantus be the insulin regimen in a cardiovascular study of Praluent? Because it is going to generate a lot of data and the majority of the costs associated with the study will be borne by Sanofi not Mannkind. I think this is a very firm sign that Sanofi is in for the long haul with Mannkind and they realize they need more data to successfully market the drug. I have been reading some of the comments on the board for a while but I registered because I liked this post enough that it motivated me to register so I could respond. Does any one have other links to ongoing research studies involving Afrezza? They will be much appreciated.
I like the way you think. Trial costs are very expensive. Nice contribution.
To my knowledge, there are four post-marketing trials required by the FDA. You can call three of them up by typing "SAR439065" in the Search Box located at the U.S. National Institutes of Health website: clinicaltrials.gov/. One is complete, two are ongoing and the fourth, a long-term lung safety study, is being negotiated between Sanofi and the FDA to work out the protocols that will be used.
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Post by rrtzmd on Nov 6, 2015 14:41:26 GMT -5
Not for afrezza. First, note that afrezza use is not mandated. It is simply one of the available therapies for managing the patients' diabetes. Oral therapies, other rapid acting insulins such as humalog, and lantus are available as well. Given the generally accepted protocol of type 2 diabetes management, orals come first, while insulin is the very last, when all else fails, option. Also, lantus is the recommended option at that point. So it's unlikely that very many of those patients will get afrezza. Type 1 diabetics are included in the study as well, but LDL/hypercholesterolemia tends not to be a big problem with type 1s as long as their glucose is controlled. Indeed, I'm not sure why SNY included them. I think they would have a better chance of success by focusing on the type 2s where the chance is higher that the drug would contribute benefits more than just glucose control. In any case, given that most patients are already managed with injectable RAAs and would unlikely change for a study unless conditions during the study warrant it, I doubt they will see much aafrezza either. When you know type 1's who have died in their early 40's of a heart attack, your words can not easily be read. Plenty of type 1 eat a bratwurst over a potato so as not to awaken the need for insulin. How many type 1's do you know that are well controlled?
I'm afraid I don't understand what point you're trying to make. I was merely explaining why that study would not likely produce much info about afrezza. |
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Post by rrtzmd on Nov 6, 2015 14:54:05 GMT -5
Not for afrezza. First, note that afrezza use is not mandated. It is simply one of the available therapies for managing the patients' diabetes. Oral therapies, other rapid acting insulins such as humalog, and lantus are available as well. Given the generally accepted protocol of type 2 diabetes management, orals come first, while insulin is the very last, when all else fails, option. Also, lantus is the recommended option at that point. So it's unlikely that very many of those patients will get afrezza. Type 1 diabetics are included in the study as well, but LDL/hypercholesterolemia tends not to be a big problem with type 1s as long as their glucose is controlled. Indeed, I'm not sure why SNY included them. I think they would have a better chance of success by focusing on the type 2s where the chance is higher that the drug would contribute benefits more than just glucose control. In any case, given that most patients are already managed with injectable RAAs and would unlikely change for a study unless conditions during the study warrant it, I doubt they will see much aafrezza either. Where did you get this info? You seem to be forgetting the opposite opinion you gave (of the same study!) a few days ago! Hmmm... Under the tread: Afrezza (insulin human) intervention in Study of Alirocumab on Oct 27, 2015 at 7:59am you said: Whatever the results, praluent will get the limelight for anything positive. Sanofi may even resort to blaming afrezza for any bad results. I believe the reason they chose afrezza is because praluent itself is injected and they likely don't want any skin reactions that might arise from injected insulin to be blamed on praluent: Read more: mnkd.proboards.com/user/1944/recent#ixzz3qjkuoFYfSo which one is correct? They are or aren't using other prandial insulins? Oh yes the skin thing right? But what about lantus? And in my opinion you miss the reasons why Afrezza is being used: it's a perfect drug for 'metabolic syndrome' and for 'success by association'. No, I didn't forget. I merely misread the study design the first time through. I thought that they had actually excluded injectable RAAs from the available therapies. The post you quote was my attempt to try and understand why they would do something like that. Re-reading, however, I saw that I misinterpreted that one column on the far right, and that injectable RAAs WILL be available. While afrezza could be "perfect drug for 'metabolic syndrome' and for 'success by association,' I can find nowhere else where anyone associated with MNKD or SNY has made such a claim. Moreover, as I point out now, the trial does NOT mandate use of afrezza from the beginning of or at anytime during the trial -- it's merely offered as a therapeutic option. Given the flowcharts generally followed for diabetes management, type 2s are not likely to get it. Given the general market acceptance so far, most type 1s won't be on it coming into the study. I have no way of assessing the probability that they might change over to afrezza during the study. And for the "blaming" part, I stand by that. I believe SNY's shareholder conference was testimony in my favor. |
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Post by peppy on Nov 6, 2015 14:54:38 GMT -5
I saw your point, LDL/hypercholesterolemia tends not to be a big problem with type 1s as long as their glucose is controlled.
Most type ones are not well controlled. Do you listen to them?
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Post by mnholdem on Nov 6, 2015 14:55:24 GMT -5
rrtzmd
I, for one, wondered why you would even write, "Type 1 diabetics are included in the study as well, but LDL/hypercholesterolemia tends not to be a big problem with type 1s as long as their glucose is controlled," when the study is specifically testing the diabetic who LDL-C is out of control.
Primary Objectives:
- To demonstrate the superiority of alirocumab in comparison with placebo in the reduction of calculated low-density lipoprotein cholesterol (LDL-C) in patients with diabetes treated with insulin and with hypercholesterolemia at high cardiovascular risk not adequately controlled on maximally tolerated LDL-C lowering therapy.
Since MNKD investors been reading testimonials for the past 6-8 months, by many Type I diabetics who state that they have never really achieved control of their glucose levels, it seems to be that you are simply being argumentative, seeking to exclude Type I diabetics from the test to support your notion that test subjects would be those who likely have never been introduced to Afrezza, having never progressed that far past the standard metformin-to-basal treatments.
Let's, for the sake of argument, say you're right. What do you think about the possibility that Sanofi/Regeneron may initiate insulin therapy at the same time that they initiate Praluent® (alirocumab) with Type 2 DM test patients diagnosed with hypercholesterolemia? If that were the case, some of those initiates may prefer inhaling insulin to injections, and several studies indicate that needles are a major reason why early diabetics resist starting insulin treatment. There could be many Afrezza patients in this trial...
Your thoughts?
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Post by rrtzmd on Nov 6, 2015 15:29:44 GMT -5
rrtzmd
I, for one, wondered why you would even write, "Type 1 diabetics are included in the study as well, but LDL/hypercholesterolemia tends not to be a big problem with type 1s as long as their glucose is controlled," when the study is specifically testing the diabetic who LDL-C is out of control.
Primary Objectives:
- To demonstrate the superiority of alirocumab in comparison with placebo in the reduction of calculated low-density lipoprotein cholesterol (LDL-C) in patients with diabetes treated with insulin and with hypercholesterolemia at high cardiovascular risk not adequately controlled on maximally tolerated LDL-C lowering therapy.
Since MNKD investors been reading testimonials for the past 6-8 months, by many Type I diabetics who state that they have never really achieved control of their glucose levels, it seems to be that you are simply being argumentative, seeking to exclude Type I diabetics from the test to support your notion that test subjects would be those who likely have never been
to Afrezza.
"...why you would even write..." Well, because, unless there's genetic element present, LDL/hypercholesterolemia simply isn't a big problem in well-controlled diabetics. Not only that, but just in the past couple of years, research has indicated that LDL elevation in type 1 diabetics may not be as significant as previously assayed: Too much emphasis on LDL in type 1 DM
Testimonials are fine and may be correct, but people who haven't had any problem controlling their glucose are hardly likely to testify to their success, wouldn't you agree? In other words, "testimonials" represent a biased sample. I'm afraid I don't understand what you mean by "seeking to exclude Type I diabetics from the test to support your notion that test subjects would be those who likely have never been to Afrezza." I'm not seeking to exclude anyone. I'm merely pointing out that it's not likely that many of the people being recruited to the trial will come in on afrezza. Type 1s that come in with LDL/cholesterol issues that meet the criteria, will likely be on injectables to begin with. Since they are seeking to establish the effect of praluent, it wouldn't make much sense to switch the insulin regimen until it was clear that the praluent isn't working. And even if they do switch, there's no way to tell whether the patient might be switched to afrezza or some other drug, since it appears that would be at the therapists discretion. |
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Post by patryn on Nov 6, 2015 15:47:52 GMT -5
You can't have it both ways. You can't claim that SNY set up the trial to use Afrezza as a scapegoat and then out of other side of your mouth claim that most of the subjects in the trial won't be using Afrezza.
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Post by peppy on Nov 6, 2015 15:58:28 GMT -5
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Post by jpg on Nov 6, 2015 18:21:51 GMT -5
rrtzmd
There are so many inconsistencies with most of what you say that it gets hard to even have exchanges with you. You use md in your name. I am more and more skeptical of that claim. Most MDs have a basic understanding of lipids and metabolic syndrome and the basic knowledge of how to read a simple trial design (which you have consistently failed to do properly).
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Post by rrtzmd on Nov 7, 2015 0:53:09 GMT -5
You can't have it both ways. You can't claim that SNY set up the trial to use Afrezza as a scapegoat and then out of other side of your mouth claim that most of the subjects in the trial won't be using Afrezza. I'm afraid that I don't see how you arrived at the opinion that I claimed that "SNY set up the trial to use afrezza as a scapegoat." I never said nor implied any such thing. I did say that it wouldn't surprise me that if the trial failed, SNY would try to lay off the blame from praluent onto other factors including afrezza -- something which SNY in fact did in their conference call alluding to poor afrezza sales as contributing to SNY's mediocre performance overall. However, that is decidedly not "designing" the trial to make afrezzza the scapegoat. I also noted that I originally misread the trial description. I didn't read it closely the first time and thought that the trial would restrict participants to afrezza. That was an error on my part. Closer study revealed that for both arms: "The following background therapies: antihyperglycemic agents, statins, and other lipid modifying therapy will be administered as applicable or as per Investigator's discretion." In other words, patients come into the study on whatever medications they are currently taking and continue as such until the investigator decides to make a change. If the investigator decides a change is required, there is no restriction on the options available -- any currently available agent may be used. As regards how many subjects will use afrezza, I think it should be obvious that a random sample of diabetics would not produce many patients on afrezza. Therefore, it's unlikely that many trial recruits will be on afrezza coming in. As I said, there's no way to assess what therapeutic changes might be made subsequently. Given the current level of market acceptance of afrezza and the investigators freedom in choosing therapeutics, I don't see that afrezza necessarily would be more accepted during the trial. |
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Post by rrtzmd on Nov 7, 2015 0:56:27 GMT -5
rrtzmd There are so many inconsistencies with most of what you say that it gets hard to even have exchanges with you. You use md in your name. I am more and more skeptical of that claim. Most MDs have a basic understanding of lipids and metabolic syndrome and the basic knowledge of how to read a simple trial design (which you have consistently failed to do properly). Could you be just a little bit more specific as to what "inconsistencies" you found? |
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Post by patryn on Nov 7, 2015 2:56:29 GMT -5
You can't have it both ways. You can't claim that SNY set up the trial to use Afrezza as a scapegoat and then out of other side of your mouth claim that most of the subjects in the trial won't be using Afrezza. I'm afraid that I don't see how you arrived at the opinion that I claimed that "SNY set up the trial to use afrezza as a scapegoat." I never said nor implied any such thing. I did say that it wouldn't surprise me that if the trial failed, SNY would try to lay off the blame from praluent onto other factors including afrezza -- something which SNY in fact did in their conference call alluding to poor afrezza sales as contributing to SNY's mediocre performance overall. However, that is decidedly not "designing" the trial to make afrezzza the scapegoat. I also noted that I originally misread the trial description. I didn't read it closely the first time and thought that the trial would restrict participants to afrezza. That was an error on my part. Closer study revealed that for both arms: "The following background therapies: antihyperglycemic agents, statins, and other lipid modifying therapy will be administered as applicable or as per Investigator's discretion." In other words, patients come into the study on whatever medications they are currently taking and continue as such until the investigator decides to make a change. If the investigator decides a change is required, there is no restriction on the options available -- any currently available agent may be used. As regards how many subjects will use afrezza, I think it should be obvious that a random sample of diabetics would not produce many patients on afrezza. Therefore, it's unlikely that many trial recruits will be on afrezza coming in. As I said, there's no way to assess what therapeutic changes might be made subsequently. Given the current level of market acceptance of afrezza and the investigators freedom in choosing therapeutics, I don't see that afrezza necessarily would be more accepted during the trial. Here is what you actually said: "Now, the thing is, if the trial is successful and praluent works, it will be given all the credit since it is a "big ticket" item with all of the profit going to SNY. On the other hand, if it doesn't work out in praluent's favor, it wouldn't surprise me if SNY went looking for something to blame it on -- that happens frequently after failed trials -- hence the possibility that afrezza may find itself being the one getting blamed." mnkd.proboards.com/post/42594You can choose to interpret your words however you like, but I leave it to the others reading to see what your own words have to say regarding the trial. |
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Post by rrtzmd on Nov 7, 2015 11:41:03 GMT -5
I'm afraid that I don't see how you arrived at the opinion that I claimed that "SNY set up the trial to use afrezza as a scapegoat." I never said nor implied any such thing. I did say that it wouldn't surprise me that if the trial failed, SNY would try to lay off the blame from praluent onto other factors including afrezza -- something which SNY in fact did in their conference call alluding to poor afrezza sales as contributing to SNY's mediocre performance overall. However, that is decidedly not "designing" the trial to make afrezzza the scapegoat. I also noted that I originally misread the trial description. I didn't read it closely the first time and thought that the trial would restrict participants to afrezza. That was an error on my part. Closer study revealed that for both arms: "The following background therapies: antihyperglycemic agents, statins, and other lipid modifying therapy will be administered as applicable or as per Investigator's discretion." In other words, patients come into the study on whatever medications they are currently taking and continue as such until the investigator decides to make a change. If the investigator decides a change is required, there is no restriction on the options available -- any currently available agent may be used. As regards how many subjects will use afrezza, I think it should be obvious that a random sample of diabetics would not produce many patients on afrezza. Therefore, it's unlikely that many trial recruits will be on afrezza coming in. As I said, there's no way to assess what therapeutic changes might be made subsequently. Given the current level of market acceptance of afrezza and the investigators freedom in choosing therapeutics, I don't see that afrezza necessarily would be more accepted during the trial. Here is what you actually said: "Now, the thing is, if the trial is successful and praluent works, it will be given all the credit since it is a "big ticket" item with all of the profit going to SNY. On the other hand, if it doesn't work out in praluent's favor, it wouldn't surprise me if SNY went looking for something to blame it on -- that happens frequently after failed trials -- hence the possibility that afrezza may find itself being the one getting blamed." mnkd.proboards.com/post/42594You can choose to interpret your words however you like, but I leave it to the others reading to see what your own words have to say regarding the trial. I see essentially nothing wrong with the statement, "Now, the thing is...etc." I believe that it is perfectly accurate. Go find a trial that has failed and I'm willing to bet the company, in announcing the results, somewhere has tried to shift the blame away from the drug itself and onto whatever happens to be available and suitable. Sometimes they blame the patients for not complying, sometimes the investigators for not following procedure, sometimes it was a bad batch, sometimes the design is at fault, etc. This is simply what they do to deflect blame from their product. As far as afrezza specifically, at the time I wrote that comment, I was under the impression that afrezza was to be the only prandial insulin, so I thought it could be a convenient target if the trial failed. But now realizing that the investigators will have their choice of any drug they wish to manage the diabetes, I doubt SNY would blame any of the drugs being utilized if the trial failed. |
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Post by rrtzmd on Nov 7, 2015 11:56:02 GMT -5
rrtzmd
I, for one, wondered why you would even write, "Type 1 diabetics are included in the study as well, but LDL/hypercholesterolemia tends not to be a big problem with type 1s as long as their glucose is controlled," when the study is specifically testing the diabetic who LDL-C is out of control.
Primary Objectives:
- To demonstrate the superiority of alirocumab in comparison with placebo in the reduction of calculated low-density lipoprotein cholesterol (LDL-C) in patients with diabetes treated with insulin and with hypercholesterolemia at high cardiovascular risk not adequately controlled on maximally tolerated LDL-C lowering therapy.
Since MNKD investors been reading testimonials for the past 6-8 months, by many Type I diabetics who state that they have never really achieved control of their glucose levels, it seems to be that you are simply being argumentative, seeking to exclude Type I diabetics from the test to support your notion that test subjects would be those who likely have never been introduced to Afrezza, having never progressed that far past the standard metformin-to-basal treatments.
Let's, for the sake of argument, say you're right. What do you think about the possibility that Sanofi/Regeneron may initiate insulin therapy at the same time that they initiate Praluent® (alirocumab) with Type 2 DM test patients diagnosed with hypercholesterolemia? If that were the case, some of those initiates may prefer inhaling insulin to injections, and several studies indicate that needles are a major reason why early diabetics resist starting insulin treatment. There could be many Afrezza patients in this trial...
Your thoughts?
I'm sorry, but I only just noticed that I overlooked the second part of your post about "the possibility that Sanofi/Regeneron may initiate insulin therapy at the same time that they initiate Praluent® (alirocumab) with Type 2 DM test patients diagnosed with hypercholesterolemia...There could be many Afrezza patients in this trial." Indeed, there could be. But, as I understand the trial description, this is basically a "real life" trial. The investigators will be able to follow any protocol they wish to manage the diabetes aspect. They will be free to start or stop afrezza if they or the patient wishes. However, like I said, while starting insulin and/or afrezza might be encouraged, it is not mandated. Consequently, given that in the flowchart of type 2 treatment, insulin is the last resort, I wouldn't anticipate a lot of data regarding afrezza coming from the trial. |
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Post by centrn on Nov 7, 2015 12:01:44 GMT -5
If that is your logic, why wouldn't Sanofi blame something that they have no financial interest in? To suggest that they would shift the blame to one of their other products, Afrezza, rather than a myriad of other possibilities would suggest that you either feel Sanofi is stupid, or purposely trying to undermine Afrezza. Quite an interesting proposal.
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