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Post by agedhippie on Apr 14, 2024 9:43:24 GMT -5
... Now lets look at the Cipla trail description. Again from the filing... "Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of Prandial Technosphere® Insulin Inhalation Powder Versus Placebo Inhalation Powder in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Oral Antidiabetic Drugs Over a 24-week Treatment Period."... OK - isn't that the SoC for T2s? After the first fails then you add the second and the third and finally get to insulin. How would you have performed the trial? To follow the SoC you keep them on their current med and add which is what they did. Do you want to take them off their current meds? Maybe Cipla dosed better. I have no idea what they did which is the reason I would like to see the trial results. Did they add afrezza to GLP1s? These were not part of the 175 trial. I would have performed the trial exactly as they did here. Cipla just want to get Afrezza approved so they can sell it in India. GLP-1 is completely irrelevant in this trial because the comparison is between Afrezza and pure Technosphere with nothing else in their treatment changed, so if people are using GLP-1 (and it would have to be Rybelsus as the only oral GLP-1) they will be in both groups and cancel out.
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Post by agedhippie on Apr 13, 2024 16:16:03 GMT -5
...To win we need studies or a huge price cut to become SoC for the T2s. The 175 and hopefully Cipla have showed superiority but cost is a show stopper. Afrezza has already shown superiority in the 175 trial, and I am certain it will again in the Cipla trial since the protocol used was identical. The real question is superior to what? Lets look at the description from the official filing... "Insulin-naive subjects with Type 2 Diabetes Mellitus who are sub-optimally controlled on either maximum tolerated dose of metformin or maximum tolerated dose of metformin plus one or two other oral anti-diabetic medications will have either Prandial Technosphere® Insulin or Technosphere Powder (placebo) added to their oral antidiabetic drugs."Now lets look at the Cipla trail description. Again from the filing... "Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of Prandial Technosphere® Insulin Inhalation Powder Versus Placebo Inhalation Powder in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Oral Antidiabetic Drugs Over a 24-week Treatment Period."Notice any similarities? The trial showed that Afrezza is superior to Technosphere powder alone (no insulin) in patients where oral meds were already failed ("sub-optimally controlled"). In other words is Afrezza superior to a placebo? Of course the answer was yes. This is why the 175 trial, and the Cipla trial, are literally table stakes and nobody cared. If you want to move the needle then you need the expansion trials that MNKD are starting to do now. If you expect the Cipla trial to change anything I would ask why.
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Post by agedhippie on Apr 13, 2024 10:13:18 GMT -5
"Thats not actually correct. Going into 2023 with Tyvaso DPI picking up factory costs afrezza was already break-even." I don't think that is how accounting works. Costs have to be apportioned. You cannot have one line pick up the costs for another line in a product breakeven calculation. What DPI does do is lower the overall cost of manufacturing so you are apportioning a smaller number overall. Breakeven calculations should also include fixed costs like their percentage of SG&A, but sometimes those are left out to pad the numbers.
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Post by agedhippie on Apr 11, 2024 15:22:54 GMT -5
It is rather fascinating how anyone could possible, or would even want to, remain financially invested in a company that had a management team/CEO/BOD whom he/she despises. This may be a great psychological research topic for a grad student one day. Easy, You believe that the product is so good that although the management team/CEO/BOD are terrible the company will succeed in spite of them. As a hot take I would argue that AMZN is an example and I hold a lot of their stock.
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Post by agedhippie on Apr 10, 2024 8:43:12 GMT -5
Having now gone through the transcript of LQDA's presentation at the Needham conference there are a couple of takeaways that are interesting for Tyvaso DPI.
The chief one is that LQDA believes that the PH-ILD population is actually at least twice the size currently believed because of significant under-diagnosis. I suspect they may well be right since there is not a lot of incentive currently to test for PH-ILD as it previously was untreatable.
The second is that they believe DPI can become the first line med over oral meds since apparently oral meds have a lot of GI side effects. The latter would mean UTHR would have to cannibalize their oral line, but they have already been willing to cannibalize their Tyvaso Nebulizer line so if threatened they may do so which would be good for Tyvaso DPI sales.
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Post by agedhippie on Apr 9, 2024 8:32:54 GMT -5
They probably never progress because they die of a heart attack. ... That's not the case. Look at the UKDPS data if you want to learn about this. I should be clearer here. In Type 2 glucose levels are just one aspect of a broken metabolism along with high blood pressure, weight gain, cholesterol problems, etc. This is why statins are more or less mandatory (although I dislike this.) What the UKDPS data does show is that the heart risk is not correlated to glucose levels independently of lipids.
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Post by agedhippie on Apr 8, 2024 23:00:50 GMT -5
... I don't know of anywhere in the world where insulin is not the last choice, not least because many never progress to the point where it is necessary. They probably never progress because they die of a heart attack. ... That's not the case. Look at the UKDPS data if you want to learn about this.
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Post by agedhippie on Apr 8, 2024 7:11:34 GMT -5
Doctors here in the U.S. have also been taught that putting you on insulin must be the last resort because you could die. A far bigger problem is that amongst Type 2 diabetics insulin is seen as a mark of failure and that your diabetes is terminal. Their thinking goes that they have worked through a series of treatment and have now arrived at insulin after which there is nothing else. I don't know of anywhere in the world where insulin is not the last choice, not least because many never progress to the point where it is necessary.
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Post by agedhippie on Apr 5, 2024 17:12:36 GMT -5
... I don't know what will happen in India. They have Universal Health Coverage but afrezza will probably will not be provided for free. Lets see what Cipla can do with it. ... The universal health coverage drugs have to be generics. I think that rules out Afrezza.
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Post by agedhippie on Apr 5, 2024 13:00:13 GMT -5
If the results from inhale-1 look like the preliminary results from inhale-3 superiority could be coming and that will be difficult to argue about when coupled with safety. Lipohypertrophy may become a secondary issue and yes its very real in kids maybe even more so than adults. The primary outcome is a test for non-inferiority. There are superiority test in the secondary outcomes, but those parts and not the whole. What matters to the endos is the primary as it represents the overall impact.
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Post by agedhippie on Apr 3, 2024 16:41:52 GMT -5
Forgive my naïveté but now that India trial results are in and presumably positive, would MannKind and Cipla be finalizing the marketing agreement right about now? Possible upfront cash? What do you think? I’m not expecting a $Billion but $50-100 million would be a nice addition to our coffers. Am I being unreasonable? Greedy? The results were positive, Cipla are allowed to sell Afrezza in India. The agreement makes Cipla exclusively responsible for marketing and sales in India so there is unlikely to be a marketing agreement. However, the original PR mentions a regulatory milestone payment so that might have been hit.
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Post by agedhippie on Apr 3, 2024 8:26:33 GMT -5
You are probably right. But on the face of it, ""Cipla has got a go-ahead ..... to import and market Human insulin inhalation powder." I thought that was indication of a marketing authorization. They have the go ahead from the panel. In theory they should get the marketing authorization as long as they do not get Shkrelied. What I would like to see are the trial results. Here is their website if anyone can find them. cdsco.gov.in/opencms/opencms/en/Home/I have posted this before - ctri.nic.in/Clinicaltrials/showallp.php?mid1=45751&EncHid=&userName=CiplaNo results are posted which is common. If you look at any clinical trials site they usually don't have results posted. MNKD may care more about the results than Cipla does as it was just a barrier to release for them. I would have thought MNKD could have done a PR announcing the approval, and trailing the results at a future venue to build visibility.
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Post by agedhippie on Apr 1, 2024 22:00:40 GMT -5
FYI: ... However, the nod is subject to the condition that the firm should conduct an active post-marketing surveillance study (PMS) in the country. ... That is actually very useful for MNKD. There is still the same requirement outstanding on them from the FDA so if the CIPLA study can be leveraged to cover that ...
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Post by agedhippie on Mar 30, 2024 10:04:18 GMT -5
That's standard. I think everyone does that. I certainly have as has everyone I know. I don’t know what the policy was for executives, but the last company I worked at had a written policy they would sell a portion of vested RSU shares and pay taxes and the remainder was delivered to the employee. That makes their life a lot simpler because it ensures the taxes get paid. It makes no sense to pay cash since the reason why you didn't want to sell stock to pay tax would be to preserve your stock. You could get exactly the same effect by sell the stock and using the cash to replace the stock - in other words it is a wash. The difference is that with selling the stock you are making the logistics the brokers problem I seem to remember that there is, or used to be, a third option. You can pay the tax on the entirety of the RSU grant when it is granted rather than as it vests. If I expect the stock to double then paying when it is granted will save me tax down the line as it is based on the price at grant, but if I leave before the vesting then I lose the prepaid tax. No one can predict their future career so it's a high risk strategy. And to be clear; this is not tax advice, it's my recollections from the past!
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Post by agedhippie on Mar 30, 2024 0:10:23 GMT -5
That's standard. I think everyone does that. I certainly have as has everyone I know.
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