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Post by agedhippie on Feb 6, 2023 12:40:43 GMT -5
A lot of minor wording changes and clean ups generally. This page has all the links: www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022472Looking at the letter it's a notification that the waiver to only have a 1/2 page highlights section has expired and some minor changes. Since the highlights has been longer than a 1/2 page for a while now that bit is redundant! They have removed duplication between the highlights and the black box. The dosing section has changed from this: -----------------------DOSAGE AND ADMINISTRATION----------------------
Administer using a single inhalation per cartridge (2.1)
Administer at the beginning of a meal (2.2)
Dosing must be individualized (2.2)
Before initiating, perform a detailed medical history, physical
examination, and spirometry (FEV1) in all patients to identify potential
lung disease (2.5)to this: -----------------------DOSAGE AND ADMINISTRATION---------------------- • Only administer via oral inhalation using the AFREZZA inhale (2.2)
• Administer at the beginning of each meal (2.2)
• See full prescribing information for the recommended starting
mealtime dosage in insulin-naïve patients and patients who are
using subcutaneous mealtime insulin or pre-mixed insulin (2.3)
• Modify dosage based on the patient's metabolic needs, blood
glucose monitoring results, and glycemic control goal (2.3)
• If blood glucose control is not achieved in patients requiring high
AFREZZA doses, consider discontinuing AFREZZA (2.4)They have removed this bullet from the Warnings and Precautions (which makes sense since it's directly addressed by the black box): Acute Bronchospasm: Acute bronchospasm has been observed in
patients with asthma and COPD. Before initiating, perform spirometry
(FEV1) in all patients. Do not use in patients with chronic lung disease.
(2.5, 4, 5.1)
as well as a bullet saying be careful when you change insulin types. The Full prescribing information section has been somewhat reordered but on a (very) quick scan I can't see anything significant. Notably the RAA to Afrezza conversion chart is unchanged.
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Post by agedhippie on Feb 6, 2023 10:28:49 GMT -5
Aged - this is NOT conflating two topics. The Medicare requirement to get a CGM covered by Medicare - The patient is insulin-treated with three or more daily administrations of insulin or a continuous subcutaneous insulin infusion (CSII) pump; - The patient's insulin treatment regimen requires frequent adjustments based on BGM or CGM testing results; Based on this Robert Ford is missing a major market. If he can get a one shot a day basal added he can get GPs to prescribe insulin earlier to T2s. This is what he said in the interviews he gave. The problem with the argument is obvious and the T2 on a basal in not making frequent adjustments. The difference between the T1 and the T2 is the T1 is about TIR but the T2 is about Treat to Target - T3. This is very different. However, afrezza is PERFECT for T3. I would argue the only thing which can do this. Robert's job is to sell CGMs. If he can do it by getting GPs to prescribe afrezza he gets what he needs. At one level he could care less if they ever use it as long as its prescribed. So, in this case it would be Abbott's job to get afrezza prescribed as a means to an end. In summary; Abbott have a change to Medicare coverage filed that will allow basal only users to get a CGM . As such they have no need to go through trying to get the SoC changed to promote Afrezza. Without a change to the SoC Afrezza, along with RAA, remains the last step in the SoC. Now the details. This is from the proposed change that Abbott submitted which the CMS are currently reviewing: The beneficiary is insulin-treated with at least one daily administration of insulin; or,That covers basal insulin as do the five clinical trials they submitted in support showing that using a CGM reduces the hBA1c of a Type 2 on basal insulin. Once that passes Abbott will not need to get mealtime insulin more widely used, basal alone will be sufficient. This is what I mean when i say if you want to change things you need trial data. Now you talk about changing the way T2 is treated (I am not arguing that this is a bad idea btw), and that means changing the SoC. You are jumping from "this is how people should be treated" to "and if they are treated like that Abbott get more business" and skipping over the fact that the SoC defines a different path so you would need to get the SoC changed before this was viable.
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Post by agedhippie on Feb 6, 2023 0:14:05 GMT -5
Again, just want to confirm..you’re neither long or short the stock, don’t currently use Afrezza, and yet you spend your days on a stock message board… Again, yup.
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Post by agedhippie on Feb 5, 2023 20:58:59 GMT -5
Sigh - so after going round and round it sounds like you are in violent agreement. The label does not need a "black box" a simple warning would do resulting in no FEV. ... It would be interesting to see where the members of that FDA team are today and if any took BP jobs. If there was no black box then there would be no need for FEV, absolutely agreed. However, there is a black box and that's unlikely to go away without data (there is a higher bar for removal than labelling). I would be shocked if a large percentage of that FDA team were not in BP since we are talking about events nearly a decade ago. People will have changed employers a couple of times on average over that period and short of a career change where else can they go?
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Post by agedhippie on Feb 5, 2023 20:19:47 GMT -5
... He [Abbott/Libre] is hoping they can get CMS to approve CGMs for just basal use with T2s. I don't know if that will happen but what I do know is they will provide little value for that use case. CGMs for T2s are all about "Treating to Target" (T3) while for T1s its TIR. A basal insulin can not T3 and nor can an antiglycemic. Only an RAA or afrezza can and what T2 wants an RAA when they can get afrezza for $35. What GP wants to prescribe an RAA and risk a hypo? ... This conflates two separate topics; getting CGMs approved for basal users, and getting doctors to prescribe Afrezza. The Libre, and Dexcom, is already approved for Medicare if you are using mealtime insulin like Afrezza. They have been lobbying to extend that to basal insulin users (people on the prior step) as well and it looks like it will be approved since there is the trial data from five trials to show better hBA1c and/or TIR. The approvals use case is people taking insulin once or twice a day (the twice is to cover Levemir which is a twice daily basal.) The step up from basal only to mealtime insulin is already established in the SoC. Getting that mealtime insulin to be Afrezza rather than RAA is Mannkind's job. In addition if Mannkind want to change the SoC then the CGM makers have shown how to do that here - trial data and the more the better (five trials in this case.)
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Post by agedhippie on Feb 5, 2023 19:49:27 GMT -5
^This. Post launch trials are what drives sales. That phase 3 trial almost never has market changing results because it's the gateway to approval so everyone is incredibly conservative as failure is not an option. Post launch you do large scale trials to highlight the areas you do well in to raise visibility, and then there is label expansion to expand your market. Numbers count, studies like ABC tell you if it's worth doing a real trial but they will not move the needle alone - that's the job of the real trial. ... Mounjaro??? Post launch studies??? Can you point me to a post launch study? Certainly, look at the clinical trials site. I suggest searching on Tirzepatide rather than Mounjaro though. I think the series you are looking for is the SURPASS family.
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Post by agedhippie on Feb 5, 2023 11:46:47 GMT -5
... The bottom-line of this stream of conciousness is I’m firmly in agreement with whoever says the main problem with breaking into the T2 market is the ADA Standard of Care and the obvious lack of full-scale post-launch clinical studies proving superiority (not non-inferiority) and SAFETY. SAFETY DAMNIT!!! Minimal studies = minimal sales. ^This. Post launch trials are what drives sales. That phase 3 trial almost never has market changing results because it's the gateway to approval so everyone is incredibly conservative as failure is not an option. Post launch you do large scale trials to highlight the areas you do well in to raise visibility, and then there is label expansion to expand your market. Numbers count, studies like ABC tell you if it's worth doing a real trial but they will not move the needle alone - that's the job of the real trial. You effectively can get a free CGM today, both Dexcom and Libre will run on your phone and don't need a standalone receiver. That leaves just the sensors (the razor blades in this model) and those are not free as it's where they make their money. Both companies will give you a free starter pack of sensors (one in the case of Dexcom, two from Libre) if you are on insulin.
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Post by agedhippie on Feb 5, 2023 0:21:21 GMT -5
Black box label: WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE. Bronchospasm is why there is the black box label, not decreased lung capacity. The FDA justified their stance in that section you highlighted - "observed instances of acute symptomatic bronchospasm." Aged - how many cases of acute bronchospasm have been reported since approval??? Didn't we also have the cancer issue from the 3 guys who worked in a heavy metal smelting plant who also smoked and that was after what 12 weeks or 24 weeks of afrezza use they got cancer, good grief! Do we really need mandatory FEV testing??? I am good with the black box saying if you have a history of bronchospasm you may incur acute bronchospasm taking this so don't. I even think optional FEV testing is a good idea but required??? What we have learned is afrezza user's lungs are no worse but sometimes better. Getting a baseline is a great idea but should not be in the way of a prescription which was Sanofi's excuse as why it didn't sell. I think your friends did everything they could to stop afrezza but I think the train is starting to leave the station and its time to clean up the label. I think even you who told us your endo would not prescribe because of lung damage concerns can now admit the concerns were unfounded. I think we can all agree no one's lungs are going to explode taking afrezza or even Tyvaso DPI. Lets revisit this all again. Sigh. How many cases of bronchospasm? Well I certainly don't know, and if the label is doing it's job the answer should be zero. I believe that the cancer study is still an outstanding requirement. The FDA has been granting waivers because there is isn't a sufficiently large population of Afrezza users yet to get a statistically meaningful result. The mandatory FEV test is because that's how they detect lung disease for the black box label. There is no requirement beyond the initial FEV test. My friends! Lol. The truth is that the lack of trial results did that without any help. Mannkind never gave the endos a reason to change so they stayed with what they knew. Endos are not about to experiment on their patients without data and I, as someone they would be experimenting on, am more than happy with that. The lung damage concerns expired years ago. The fibrosis from Exubera was found in the first two years. That hasn't been a concern for six years now (Afrezza launched eight years ago)
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Post by agedhippie on Feb 4, 2023 19:27:38 GMT -5
... In addition, we note that, as discussed above, the risk of bronchospasm was identified with respect to Afrezza based on observed instances of acute symptomatic bronchospasm. FEV1 measurements were considered confirmatory but were not the primary basis of the concern.... Hmmmm - " However, the use of spirometry studies reflects a conservative approach to assessing bronchospasm risks that is not always needed or used for new inhalation products." So that's from the FDA, that's interesting. Did the FDA just provide the justification for its removal from the afrezza label? Not only is afrezza not a new product but I have not heard of bronchospasm as being an issue. Lets hope this is part of the label change which is being worked with the dosing change in front of MIDD right now. Black box label: WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE. Bronchospasm is why there is the black box label, not decreased lung capacity. The FDA justified their stance in that section you highlighted - "observed instances of acute symptomatic bronchospasm."
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Post by agedhippie on Feb 3, 2023 15:42:57 GMT -5
You are going to have a pretty good idea of what the numbers will be based on UTHR's results a week or two earlier.
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Post by agedhippie on Feb 3, 2023 13:58:36 GMT -5
Party might be over for Tyvaso DPI UTHR under selling pressure and LQDA exploding upward on more a million shares. News is on the wire. Your post was a little challenging to interpret. Not sure what you meant by "LQDA exploding upward on more a [sic] million share". For comparison MNKD currently averages about 4,000,000 shares traded per day.
Also, can you please provide a link for the "News is on the wire"? I don't think anyone actually said what they news on the wire was. It was that the PTAB had rejected UTHR's appeal and reaffirmed that '793 was unpatentable. This link has the relevant information: finance.yahoo.com/news/patent-trial-appeal-board-ptab-213900341.html
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Post by agedhippie on Feb 3, 2023 13:47:09 GMT -5
Does Liquidia have any long term safety data of their PRINT dry powder? I know MannKind has extensive long term data of their dry powder FDKP carrier particle. Good question. They must have safety data to have gotten approval, but over what timescale they have data for the PRINT technology I don't know.
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Post by agedhippie on Feb 3, 2023 11:30:42 GMT -5
Clement think you have your dates wrong. The 3 year exclusivity runs from time of NDA approval date 05/23/2022 not the submission date, So May 2025. search for "Exclusivity is granted upon approval"
Tyvaso DPI should fall under 3. "Other" Exclusivity - 3 years for a "change" if criteria are met:
Approval of Tyvaso nebulizer for PH-ILD was in March 2021. Does T-DPI for PAH in May 2022 get a new start on the clock? My reference link above is where I got the March 2024 date and it's info from Liquidia's Q2 EC. Maybe LQDA obfuscated. IDK. This is from their CEO on the LQDA Q3 2022 earnings call in response to an analyst question on PH-ILD:
The only reason they wouldn't get the approval is if the extension study failed which unlikely because the main trial would have failed and it didn't, but if that was the case they would have far bigger problems!
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Post by agedhippie on Feb 2, 2023 18:07:59 GMT -5
Here's what LQDA's CEO said about the IPR battle... "Depending on the outcome of the appeals, the scheduling of oral arguments and the possibility of summary affirmance, we remain confident that we will reach final legal resolution in late 2023 or the first half of 2024.” That appeals timeline may not sound very "appealing" if you're a LQDA shareholder. Maybe that's why the analyst support appears to be evaporating. Wake me up about LQDA late in 2023 or the first half of 2024. This is pretty much smack on the money. I went over why in a previous post, but the TLDR is that this is a well trodden path. The incumbent knows that they will ultimately lose the action, but they want to delay the competitor for as long as possible by appealing all the way down the line. That line runs out, assuming the past record holds, mid-2024. It's possible, but unlikely, that things may move faster hence the late 2023 date (I'm sceptical). Can LQDA challenge UTHR? Not really. LQDA is aiming for a percentage of the market. They aren't a UTHR, they only need about a small part to be rolling in money and they can get that by undercutting UTHR - the playbook they used in the Remodulin market. Ultimately LQDA's success or failure is pretty much irrelevant unless UTHR screw up on a truly momentous scale. My feeling is that this is the same approach Mike is using with Afrezza; there is no way for MNKD to keep up with the big boys, but a corner of that market would do very lucrative.
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Post by agedhippie on Feb 2, 2023 8:52:42 GMT -5
... The Pump switch trial sounded like a good start and I am sure Aged will be happy to hear a bigger trial is coming. For us here as predicted afrezza would kick a.. or so it seems it did based on Mikes comments. You don’t need to carb-count may be a bridge too far for Aged but we will see. ...The pump trial in itself is insignificant (5 people per arm...) but the outcome will be a guide to whether it's worth rerunning the trial properly. A full trial could potentially be expensive because of the pumps. In the current trial they are using whatever pumps people have, but not the new 780G pumps. They would need to standardize to prove that the results aren't an artifact of the pump itself. On the plus side I think they could dump the Afrezza and pump arm because in real life nobody would do that (if I have to wear a pump I am going to use the pump for everything - it's a convenience thing). Carb counting will always matter, and Mannkind have the trial data to show how badly that goes off the rails when you ignore it (the trial they abandoned where the entire Type 1 arm had hypos).
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