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Post by esstan2001 on Jan 6, 2016 15:30:39 GMT -5
All this stuck in the mud A1C standard for evaluating- how to change the paradigm?
Why not have PWD like Sam, Eric, Clevland Clinic etc. lobby / petition / start a movement to organize an expert advisory panel of thought leader endocrinologists to develop new standards / guidelines regarding diabetes care, using the newer technologies available (CGM)? Then (for trials) define the obvious, that maintaining real time blood glucose levels within such and such a tighter range leads to less cell stress, health complications etc.-
Run these trials against injectable RAA and compare the (CGM data) blood glucose excursions, show (prove) the obvious superiority, along with some A1C data... Get the FDA into this century already.
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Post by esstan2001 on Jan 5, 2016 23:22:39 GMT -5
oy vey.
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Post by esstan2001 on Jan 5, 2016 23:13:57 GMT -5
Sanofi delayed drug to avoid $708 mln in payments, lawsuit claims By Brendan Pierson Nov 9 (Reuters) - A new lawsuit accuses Sanofi SA of stalling development of its multiple sclerosis drug Lemtrada to avoid paying out at least $708 million to rights holders under its 2011 agreement to acquire Genzyme Corp. The lawsuit, filed on Monday in Manhattan federal court by American Stock Transfer & Trust Co LLC, a trustee for the rights holders, seeks at least $236.1 million in damages. Genzyme was in the process of developing Lemtrada when Sanofi bought it. Under the merger agreement, Sanofi issued Genzyme shareholders tradable certificates entitling them to payments if Lemtrada won approval from the U.S. Food and Drug Administration by March 31, 2014, and further payments if it met certain sales benchmarks after that. Sanofi promised it would make "diligent efforts" to meet those goals, according to the complaint. Instead, the trustee alleges, it deliberately took a "slow path" to bring Lemtrada to market. ADVERTISEMENT The lawsuit claims Sanofi deliberately ignored the FDA's concerns about the designs of its clinical trials, leading the agency to deny the company's first application for approval. The trustee further claims that even after Lemtrada was finally approved in November 2014, Sanofi skimped on marketing it, while actively promoting a different multiple sclerosis drug, Aubagio. As a result, the lawsuit says, Lemtrada has failed to meet any of the sales benchmarks. The drug is expected to lose patent protection in September 2017, according to the lawsuit, further limiting its prospects. Sanofi said in a statement that it was aware of the lawsuit but did not comment on pending litigation. The case is American Stock Transfer & Trust Company LLC v. Sanofi, U.S. District Court, Southern District of New York, No. 1:15-cv-08725. (Reporting by Brendan Pierson in New York; Editing by Matthew Lewis) Mgmt would be negligent not to file a law suit against Sanofi. It has a great case on lack of Commercially Reasonable Effort. Look at who filed this lawsuit- AST&TC LLC; are they representing the company or the shareholders? Be great if they took this on for shareholders and institutions-
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Post by esstan2001 on Jan 5, 2016 19:00:52 GMT -5
To have his first public exposure in such a negative situation and no time to prepare meaningful comments other than cheerleading would be a bad start. While MNKD could not have definitive info of the deal drop for legal reasons, I am sure mgt knew things were going to go badly. I look forward to a message from Duane in the next week to ten days to announce something meaningful. For those referring to being locked in until July, I think that is the required latest date all can end. SNY is still on the hook for expenses until the divorce is finalized. That could theoretically be much sooner. I am sure Duane is in talks with SNY to be freed asap. I am also thinking that Al & Duane may be in (or are considering) a position to settle with SNY on some concessions (some debt or cost sharing forgiveness) in return for a promise not to pile on and sue SNY for lack of promotional / sales effort... seems close that a potential case can be made, and SNY is gaining a reputation.
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Post by esstan2001 on Jan 5, 2016 18:51:49 GMT -5
TEVA almost rhymes with TASE a little re-ordering, change 1 letter... PRESTO!
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Post by esstan2001 on Jan 5, 2016 8:39:01 GMT -5
For all practical purposes, the effect on blood glucose for the first 60 minutes are identical. In my reading of the curves, Afrezza's sharp rise occurs 10-15 minutes earlier than Lispro; Afrezza's rise is over at about 30 minutes, Lispro's at 45 minutes. Past that, Afrezza takes out serious area under the Lispro curve, indicating a dramatic difference (cut) in glucose infusion rate. In no way do I see the curves as being identical for the first 60 minutes. Maybe an expanded scale for the X axis would help to clarify this :-)
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Post by esstan2001 on Jan 4, 2016 12:52:04 GMT -5
Is he our first foreign moderator? And a Canuck, to boot. I don't know, I'm kinda hesitant to endorse this move, those Canadians are very sneaky people. You know, they have the Venture (aka "Vulture") exchange up north. I don't think they play fair like we do in the States, after all we have the SEC to safeguard our markets. Just sayin' I met him (and his lovely wife) at the annual meeting. He's OK. He's one of us. Just from the Great White North, that's all. Hell, Liane is practically from there too... just south of that Northern border. As you, and my kids would say, 'Just sayin.
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Post by esstan2001 on Dec 25, 2015 20:44:19 GMT -5
bioequivalence and batch consistency tests run, then a report submission to FDA, probable site inspection by FDA to ensure GMP compliance, that usually will suffice unless there is something that raises question.
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Post by esstan2001 on Dec 22, 2015 16:05:12 GMT -5
tommix321 ... yes, I've taken quite a bit of statistics as I have Ph.D. in engineering with one focus area being communication theory which is based on statistics... detecting signals in noise. I do not claim to be an expert in clinical trial design but I do know safety studies must be much longer and include more people because they are looking for the dangerous needles in the haystack. A trial for superiority is not going to be as big as the required FDA safety study, and I would guess it really could be done in 4-6 months and involving hundreds not thousands. It isn't unreasonable to look at other trials as you cite, but you should keep in mind that the trial would naturally be structured to include whatever time frame is needed for the particular therapeutic to achieve the desired result taking into account the occurrence rate they are trying to uncover. Toujeo may take longer to achieve lower A1c (that I'm not sure about), but I do know that the difference in hypoglycemia they are trying to prove is not a huge one... i.e. it would take more data. Toujeo simply does not have as significant clinical advantage as does Afrezza. The more pronounced the advantage, the smaller the trial needed to show it statistically. So there are limitations to comparing one trial against another. It does seem like you are possibly confusing variability in the population vs individual variability. In your bell curve example you are implying that if there is a wide bell curve for patients being treated for diabetes a reduction in A1c during the study might be explained by random variability. This simply isn't a valid way of looking at it. The bell curve is very wide because patients progress along it. Patients do not randomly improve and shift to the lower end of the scale. You'd need to have statistics about the changes typically seen in patients whose treatment remains the same... that would show that most patients being treated do not improve on their own without changes in their therapy. Having a control group gives hard data. "It does seem like you are possibly confusing variability in the population vs individual variability. In your bell curve example you are implying that if there is a wide bell curve for patients being treated for diabetes a reduction in A1c during the study might be explained by random variability. This simply isn't a valid way of looking at it. The bell curve is very wide because patients progress along it. Patients do not randomly improve and shift to the lower end of the scale."? I'm afraid your assessment is terribly wrong. Patients do not "progress along" a bell curve. A bell curve is formed by randomly selecting patients from, say, a diabetic population, and measuring a variable, say A1C. You collect the A1C data from these individuals and graph it. In a normal distribution, the majority of measurements will cluster around the mean. Because of individual differences, different treatments, etc, there will be variability so that more rare measurements will be distributed further and further away from the mean -- this results in the "bell": bell curveThe width of the curve reflects how much variability in the population exists for whatever your measuring. In that link, the blue curve shows that population has relatively low variability for the measure versus the red curve. If you randomly select an individual from the red population, then you will have a lower probability of selecting someone who is closer to the mean than if you select one from the blue population. Statistics is about assessing the effect of variability in deciding whether a treatment is effective or not. To do that, you randomly select subjects from your affected population -- e.g. diabetics -- and then randomly assign them to either the experimental (afrezza) group or the comparison group (RAAs). Next, you measure your variable over whatever time period you choose and then calculate the means and standard deviations for each group. Then, you want to prove that the afrezza mean is better than the RAA mean. If the means are very far apart, then likely no problem. If they are closer together, then you have to use a formula based upon the standard deviation to assess whether the difference in the means is indeed too large to be accounted for by an "accident" due to large variability within the population. Now what you're really trying to determine is the degree of overlap in the graphs: overlap of bell curvesUsing that image as reference, if you put the graphs of the two groups on the same sheet of paper, then the overlap of the green and blue graphs should not exceed 5% of the area of the graphs. The "5%" is just an arbitrary number that statisticians agreed upon for proving "significance." If there is a lot of variability -- see link -- the graphs will be wide and overlap more, making the risk of no significant difference higher. About the only way to "narrow" the graphs -- see link -- and hence improve the chance of detecting a significant difference -- is by increasing the population size. Like I said, that's why SNY chose that peculiar number of 3,270 for the toujeo trial. Their statistician assessed the variability and was able to calculate the number of patients that would most likely be required to demonstrate a significant difference. As far as how SNY determined the length of time needed, that was likely related to the choice of variable --A1C. The same would apply to afrezza. If they chose A1C, then they would need probably a minimum of six months to detect a difference and show repeatability. Factor in recruitment, logistics, analysis, etc, and you're looking -- most likely with extreme optimism -- at a minimum of a year. Jesus H. Christ, I sure hope that SNY / MNKD will (get the FDA to) advance beyond A1C as the marker for superiority- include it, but include CGM data showing total blood glucose excursions, incidence of hypos, freedom of dose timing, etc such that the whole data package is overall a convincing slam dunk; I assume that the requisite paradigm change in metrics is what is taking so long to negotiate with the stuck in the mud FDEELAY bureaucracy.
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Post by esstan2001 on Dec 22, 2015 9:45:06 GMT -5
I have made many new friends here in 2015. I wish to extend to all of you my humble prayer that you will have a safe & happy holiday season, followed by a very prosperous new year!
Good fortune all.
Thank you for the excellent job you do in moderating here, and for bringing clear, pertinent information to the members of this board; You, Liane, and BD truly make this THE place to come regarding all things Mannkind. To all the moderators and long time members, and even the new ones- a Happy, Healthy Holiday and a Prosperous New Year!
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Post by esstan2001 on Dec 18, 2015 9:56:04 GMT -5
esstan2001 with so many of us scouring the internet for information, it's doubtful there's anything new that's public that escaped our attention. It's all up to those whose job it is to preserve and defend the company and it's shareholder value now... and Sanofi. Have a great weekend, I am going on an information fast (with the possible exception of some patent searches which will be captured in blog format elsewhere prior to sharing). Thanks, and you too (and good luck with the information fast- I may need one to cleanse my system too! )
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Post by esstan2001 on Dec 18, 2015 9:08:22 GMT -5
I'd be interested in a chain of clinics for MannKind investors. Those would surely pop up throughout the country and be well-attended. Oddly enough, there is actually one in my neighborhood. They have this API called "laphroaig" that they use in their treatment... though perhaps MNKD syndrome is off-label. Funny, I have been using the Special Edition Lagavulin 12 year API for my off-label treatment. What I am noticing (as of late) is that similar to a few patients on Afrezza, it is now taking increasing doses to be effective. I have a theory that this is a result of my recent poor informational intake, and that if the content reverts to what led my beliefs in the past, or if I consume a better, healthier diet of information, I suspect that the dosing requirements will go down. Come to think of it, it seems very analogous to T2 Diabetes.
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Post by esstan2001 on Dec 18, 2015 8:57:02 GMT -5
I'd be interested in a chain of clinics for MannKind investors. Those would surely pop up throughout the country and be well-attended. and you proposed drug of choice would be ? ..... Oxycodone, Heroin, LSD.... what addictive substance would best solve our problems?
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Post by esstan2001 on Dec 17, 2015 15:20:46 GMT -5
I wish that I could feel like celebrating, but I don't. .....
Of course, I could be wrong and the FTC, SEC and FDA are squeaky clean and woefully understaffed, thus having nothing whatsoever to do with corruption and illegal activities on Wall Street. Yeah, Right. Sure. About as likely as a snowstorm in the Sahara (was going to say, as finding tits on a bull but did not think that quite appropriate for our audience)
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Post by esstan2001 on Dec 17, 2015 14:51:40 GMT -5
Poster on Stocktwits says SNY rep told him that TV ads will start in the first quarter of 2016. stocktwits.com/Pkgossett.... Thanks Lefty- a NY righty (yes, rare I know)
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