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Post by agedhippie on Jan 25, 2024 10:57:17 GMT -5
Aged, aside from your point causing a potential delay from PH-ILD, are there other items that can adversely affect Yutrepia approval by delay or rejection? The orange book issue is one that you also mentioned. Any others you're aware of? Just looking for ideas that make this approval not so much of a slam dunk. Thanks The only other thing I could think of is the delay while they wait for Judge Andrews to remove the stay on approval following the invalidation of the '793 patent. LQDA has filed for that but it's not yet done to the best of my knowledge. I suppose it's possible that it is that that delayed the FDA, but the PR reads more like it is entirely related to the PH-ILD amendment. Since there is no CRL they are not looking for more data or trials hence my feeling that it's related the exclusivity period and a process issue instead. There is still the trial relating to the '327 patent but I seriously doubt UTHR get an injunction given the timelines. This next comment should probably be in a different thread, but it fits here as well. My feeling at this point is that the LQDA share price is being traded for it's volatility which in turn leads to volatility and that will remain until approval. That makes it an interesting option to trade around.
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Post by agedhippie on Jan 25, 2024 7:40:15 GMT -5
Having done a quick bit of research My guess is that this is because of the exclusivity period for PH-ILD. There is a provision in the FDA regs on amendments that says if a drug is in an exclusivity period you cannot use the holder's own documents to get an approval without their permission. My bet would be that the FDA is looking to see if this applies (I strongly suspect it does) and is the cause of the delay. If the FDA decides that it applies they will hold off approval until March 2024 when the period expires. For LQDA the good news is it's not a CRL, the bad news is the delay. In some ways this ia a problem of LQDA's own making. They took a chance in using an amendment to the NDA before Yutrepia was approved for PAH hoping to accelerate the PH-ILD approval, but wound up delaying PAH approval instead. This will not stop approval, but it's going to delay it until the expiry of the exclusivity in March I would expect - that's my thought after 15 minutes research anyway.
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Post by agedhippie on Jan 24, 2024 17:23:07 GMT -5
The target due date the FDA set for themselves is 1/24/2024. The court has to lift the stay first. That may (or may not) have already been done. A good review with good links is available from agedhippie posts at: mnkd.proboards.com/post/259130/threadSo what happens since the target due date hasn't been met? The target date's a target, it's not guaranteed. The FDA has an 89% on-time rate.
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Post by agedhippie on Jan 24, 2024 16:13:17 GMT -5
You should have been at the "discussion" between Al and Ralph. It was a beauty. If it was not a 1st round TKO, it was clearly 2nd round and it was not Al on the mat. Have I mentioned Al was not a doctor? BTW - I think I have read most of Ralph's stuff. I am sticking with Al. You know what they say about fool me once. ... Getting changes to the SoC is more than trial data. ... Given the choice between DeFronzo and Al I would go with DeFronzo in a heart beat. One is a respected and highly experienced endo and the other is an brilliant engineer. If I want a pump designed I am not going to DeFronzo, equally if I want to understand the intricacies of the endocrine system I am not going to Al Mann. To be clear on this; in approving metformin in 1994 the FDA was woefully behind as usual. Metformin had been in use in Europe and Canada for over 20 years at that point. DeFronzo may have been responsible for metformin in the US, but the work had been done in Europe literally decades earlier (it was approved in the UK in 1958.) The work done in the UK, specifically the huge UKDPS trial, forms the basis of the use of metformin by producing hard outcomes data. You are right in trial data alone not being sufficient, cost is also an important consideration because of the scale of the problem.
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Post by agedhippie on Jan 24, 2024 15:58:02 GMT -5
Nobody would put you on ignore:-) This is 99% correct except we stand against Ozempic.. the weight loss drugs. And I’m sure you saw Bill‘s video on Metformin. fb.watch/pN7_rjuA3K/?mibextid=v7YzmGBill is not wrong there. The problem is that while Type 2 is progressive (I agree with him on that) the speed of progression varies quite widely. If the progression is slow enough then metformin may be all they need. Equally you could blow though metformin and be on insulin (using the current SoC) in a couple of years. Personally I don't like GLP-1 and wouldn't take it (I actually have samples sitting in my fridge), but for some people it seems to be what they need. And with weight leading to increased insulin resistance the associated weight loss can put the person into remission. As with metformin, how long that lasts depends on how aggressive the progression is, but also how fast they regain the weight lost. As with all this I am in favor of going with the best option the patient thinks they can manage. Stevil mentioned a patient he got onto Afrezza who asked to be put on GLP-1 not because Afrezza was bad or he had side effects, but because he knew he wouldn't be able to manage the dosing schedule. I want diabetics to have options, including Afrezza.
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Post by agedhippie on Jan 24, 2024 11:58:53 GMT -5
... When someone "a doctor" tells me the T2 SoC makes a lot of sense and the first step is to use metformin, yet the guy who 30 years ago who promoted and got metformin FDA approved now says its the biggest waste of time in diabetes care - yet its step 1 in the SoC - Does that make sense? ... TBH I want to be treated by a doctor using data rather than a random anonymous individual on the internet using anecdote. But to each their own. DeFronzo's position is that you should use GLP-1 as the first line treatment, insulin doesn't get a look in. There are equally respected voices on the metformin side of the argument, especially as metformin is all some people will ever need. DeFronzo identifies eight disfunctions forming Type 2 diabetes (this is pretty well understood) and GLP-1 hits them where as metformin only handles the hepatic glucose disfunction so GLP-1 is more efficient at stopping progression. There is an paper where he argues the case here: diabetesjournals.org/care/article/40/8/1121/36799/Is-It-Time-to-Change-the-Type-2-Diabetes-TreatmentAnd the rebuttal here: diabetesjournals.org/care/article/40/8/1128/36824/Is-It-Time-to-Change-the-Type-2-Diabetes-Treatment(No, they aren't the same link, it just looks like it is!) These papers are worth reading because they explain part of the pathology of Type 2 so you can see why there is a drift away from insulin as a treatment for Type 2 diabetes - it's more complex than just glucose levels. As to the SoC; no trial data, no SoC change. The SoC is evidenced based and the grading of evidence is spelt out.
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Post by agedhippie on Jan 23, 2024 23:07:26 GMT -5
The summary is UTHR and LQDA have agreed to remove the '793 patent from the lawsuit and take PAH out of the equation leaving just the '327 patent and PH-ILD. LQDA claim that since they filed before the '327 patent was in the Orange book there should be no stay on the approval (I think they will be right).
UTHR still have the exclusivity period until March 2024 for the PH-ILD indication granted by the FDA that is entirely independent of the lawsuit.
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Post by agedhippie on Jan 23, 2024 16:49:37 GMT -5
The target due date the FDA set for themselves is 1/24/2024. The court has to lift the stay first. That may (or may not) have already been done. A good review with good links is available from agedhippie posts at: mnkd.proboards.com/post/259130/threadMy feeling is that the FDA will approve it. It's a lottery though and given today's price action it's possible the FDA are not going to clear it immediately. On the other hand it could just be people taking some money off the table ahead of a binary event... There is a section in Liar's Poker where Michael Lewis, who was a bond salesman at Goldman Sachs at the time, describes himself as running a full service casino. I always felt that was the best description of the stock market I have seen.
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Post by agedhippie on Jan 23, 2024 16:23:30 GMT -5
This is a sore point. The Dexcom G6 and G7, and the all of the Libre range do not require calibration in theory. [Explaining CGM issues and why you want calibration] ...Pump loop would have same problem, yes? Yes, except they use the Dexcom G6 almost exclusively so you can recalibrate. The pump manufacturers have applied for approval for the G7 and Libre 2 Plus, but only Tandem with the t:slim pump has been approved, and the iLet Bionic Pancreas has been approved for the G7 (these went through last month). In reality CGM inaccuracies are less important to pumps than they are for humans because they dose in somewhere between 1 hour and 5 minute chunks whereas if you are dosing yourself you are working in 3 hour chunks (arguably 5 hour with RAA) at best. This short time horizon minimizes the impact of bad readings as a bad reading. TBH the same problem exists with test strips. It's a very long running complaint that meter readings between meters, and even of the same meter, vary from test to test when taken immediately. That's before you look at strip bias - for me OneTouch always tests lower than it should. As you can guess meter brands and their behavior are a source of hours of moaning amongst diabetics.
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Post by agedhippie on Jan 22, 2024 21:17:45 GMT -5
Unless you have a watch that monitors glucose levels, or a monitoring patch? These are becoming more and more common, and they will eliminate those pricks too. Very interesting. Not to be disrespectful, but do you have any links to information that those do not require re-calibration using blood samples? I think that would be big. This is a sore point. The Dexcom G6 and G7, and the all of the Libre range do not require calibration in theory. My experience in practice (and this is my experience YMMV) is that the with Libre about 1 in 5 is accurate and you cannot calibrate to remove that error as they don't support calibration. The G6 is more like 50:50 but these days I always calibrate on start up anyway. The advantage of calibration is that when things are wrong you can fix them while with the Libre you have to remember to mentally adjust every reading. I never recommend Libre for that reason. This issue is more complex than it seems because of the catheter that the sensor inserts which creates a wound. The wound needs to stabilize and for the first couple of days the readings are prone to errors. Also, to prevent inflammation that catheter is coated but the body steadily erodes the coating leading to progressively worse accuracy. All of this is why I happily use calibration despite the adverts saying that it's unnecessary.
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Post by agedhippie on Jan 22, 2024 16:32:22 GMT -5
Since that's Mike's statement you are asking the wrong person the question, you should be asking Mike. You are misquoting Mike, he was talking about GLP-1 and not Mounjaro (GLP-1/GIP). Besides, Mounjaro has not been out for two years. My feeling is that I trust what Bill or Stevil are actually seeing in patients that they treat as opposed to Mike. I am not sure what you are saying. ... [And then some irrelevant stuff about CIPLA and not Mounjaro at all]Let's try this again then. Your question to Stevil that I responded to was "Why is it as Mike has mentioned numerous times that maybe Mounjaro works for 2 years and then the numbers start to rise again?" Mike was talking about GLP-1 and never mentions Mounjaro - source: 3rd earnings call responding to a question. The exact quote is, "My guess is GLPs are going to push this off a year or two."
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Post by agedhippie on Jan 22, 2024 8:49:58 GMT -5
Continue with treat to failure SOC or give beta cells the opportunity to recover? Anything that reduces glucose levels gives the beta cells the opportunity to recover, for example weight loss. Beta cell recovery is distinct from progression of the disease.
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Post by agedhippie on Jan 22, 2024 8:45:05 GMT -5
... Let me ask you a question - you said - " Mounjaro fixes the underlying problem of insulin sensitivity and takes no work by the person using it" ... Most likely to succeed in reducing A1c with minimal effort and potentially no lifestyle change? Mounjaro." Why is it as Mike has mentioned numerous times that maybe Mounjaro works for 2 years and then the numbers start to rise again? ... Since that's Mike's statement you are asking the wrong person the question, you should be asking Mike. You are misquoting Mike, he was talking about GLP-1 and not Mounjaro (GLP-1/GIP). Besides, Mounjaro has not been out for two years. My feeling is that I trust what Bill or Stevil are actually seeing in patients that they treat as opposed to Mike.
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Post by agedhippie on Jan 21, 2024 18:45:41 GMT -5
^What he said.
The CDSCO rejected Cipla’s application to sell Afrezza without a local trial and required a trial. The quickest and easiest way to fix that is replicated the US phase 3 trial which is what they are doing.
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Post by agedhippie on Jan 21, 2024 15:47:08 GMT -5
... I am not sure if you are now moving the goal posts when it comes to the Cipla results. Are you suggesting this study won't be good enough to make imapcts to the SoC? As I have said before but you don't ever remember; (1) they are a rerun of the T2 phase 3 trial MNKD did, and (2) probably more importantly Mounjaro already gets HbA1c reductions of greater that 2.0%. So why exactly do you think CIPLA will change the SoC?
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