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Post by agedhippie on Jun 10, 2023 19:55:53 GMT -5
I do have a quote from Peter somewhere about this but in the link provided and you posted above Pete mentioned about weight loss and the possibility of this being a weight loss drug. Why would he even bring that up when it was not what the phase 1 was about??? I suppose we should check: What is the purpose of a Phase 1 trial in the FDA process? What were the primary and secondary measures for the MKC253 trial?
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Post by agedhippie on Jun 10, 2023 14:14:56 GMT -5
On the basis of current guideline recommendations, SGLT2i and GLP-1 RA with proven cardiovascular benefit are recommended in patients with T2D and ASCVD or those at high risk of cardiovascular events. Not to mention 🤔 Definitely. If you say that Trulicity is predominantly Type 2 then their TRx last month was 1.26 million. Looking at the growth charts I would guess (and it's just a guess) that in May Ozempic's sales would have been around 1.5 million. There is a big demand for GLP-1 from diabetics with GLP-1 being inserted into the step two position. Out of idle curiosity I looked at metformin TRx for last month, 7 million!
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Post by agedhippie on Jun 10, 2023 13:55:11 GMT -5
... Nobody will bite based on that trial because: ... - Because it was only a single shot we can make no statement at all about the degree of associated weight loss, is it good or bad? ... ... What Peter said is they saw the same appetite suppression without the nausea. Again no. He did not see appetite suppression with or without nausea. What he actually said was; " We believe that MKC253 represents a novel approach to the use of GLP-1 as a prandial therapy for diabetes either alone, or in combination with prandial insulin. In addition, if we are able to demonstrate the same weight reduction or satiety effects seen with long-acting analogues of native GLP-1, MKC253 may have therapeutic potential in obesity."That work was never done so right now nobody knows. That's a showstopper, no partner is going to even look at this until that question can be answered.
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Post by agedhippie on Jun 10, 2023 9:40:17 GMT -5
Wow - thanks for setting me straight "Nobody will want to roll that dice". I guess the entire idea of technosphere is ridiculous. What was Martine thinking? Its a good thing Mike bought V-Go so we can get out of the TS business. We have a $90B market opportunity and a phase 1 which showed no one died nor got a belly ache. We also have a bunch of BPs trying to get away from the shot for the diet market and all facing the same issue, their pills when loaded up with enough glp1 for weight loss cause a big belly ache. ... No, the idea that Technosphere is suitable for all drugs is what is ridiculous. Technosphere is suitable for some drugs hence Martine using it for Tyvaso (inhaled to inhaled). You seem to be falling into the trap where if all you have is a hammer, everything looks like a nail. Some drugs just aren't candidates. Nobody will bite based on that trial because: - It's a different drug, GLP-1 vs. GLP-1 analog (think human insulin vs. RAA) so it has different behavior - It was only taken once in a form that cleared rapidly (GLP-1) rather than building and maintaining a constant serum level (which requires an analog because of the half life of GLP-1) - Because it was only a single shot we can make no statement at all about the degree of associated weight loss, is it good or bad? - Taken once with fast clearance there were no side effects. Unsurprising if it is hardly in your system for long enough to modify your gut behavior. - Time to market. Putting this all the way through FDA approvals mean it will be a generation late Nobody will want to roll that dice. If MNKD want to develop this they will have to do the work themselves and I don't think they are that stupid. I will check back in a year to see who was right.
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Post by agedhippie on Jun 9, 2023 18:36:05 GMT -5
... A Pfizer TS GLP1r drug is years away but in the mean time Mike can work on selling afrezza to the kids and to the seniors. I will say IMO the Pfizer TS GLP1r drug would have a shorter development/approval time than what Albert is currently doing because the GI tract is not Alberts friend..... There is no way that Pfizer is going to take an inhaled GLP-1 drug all the way through development and trials, as you point out, taking several years when they have two pill options on the ramps. Nobody know if TS GLP would have a better GI profile because it has never been studied so it's a gamble. The killer though is that timeline; by the time they got to market things will have moved on to GLP-1/GIP and possibly beyond (Lilly are already trialing a GLP-1/GIP/Glucagon triple therapy.) Nobody will want to roll that dice. As I said before if MNKD wants to do this then their best bet is to use a Victoza generic as the API since it's about to come off patent and take it through phase 2. I can't see that happening though because of the cost, time, and development cycle of the competitors (LILY vs. MNKD is not a fair fight) involved. I expect some nibbling around the edges for PR purposes.
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Post by agedhippie on Jun 9, 2023 15:34:59 GMT -5
... The third is the MNKD model which is to license the platform and manufacture the product. MNKD needs a serious partner for this who want to be in the game. Lenny pointed to Pfizer and I think they are an excellent choice. If Albert is not interested maybe Doug Langa is. The article also says Novo is trying to develop an oral diet product. I am sure there are others too. Whats Merck doing? All three are in driving distance on Danbury. ... The reality is Pfizer's oral glp-1r development has a real issue. In their latest results they saw a 34% drop out at the higher levels which they need for the big weight reduction. MNKD has a serious potential solution which is FDA approved... Novo already has a GLP-1 pill, Rybelsus, that had a TRx last month of 266k so it's safe to say they have got beyond trying to develop a pill Pfizer has danuglipron, a pill, that has just finished Phase 2 trials. Lilly has a pill in phase 2 right now. My bet is that Pfizer drops danuglipron and goes with a second GLP-1 that they have ready for phase 2. These pharmas are all chasing the oral med market and you are extremely unlikely to pull them away to an inhaled version without compelling data which does not currently exist. MNKD does not have an FDA approved solution. You cannot put an existing GLP-1 on TS and carry over the approval because you have changed the delivery method so it becomes a new drug. If you could do that the approval of Afrezza would have been a lot faster and easier. Tyvaso could do this because it was already an inhaled drug.
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Post by agedhippie on Jun 9, 2023 12:00:32 GMT -5
The most common side effects of Victoza® may include nausea, diarrhea, vomiting, decreased appetite, indigestion, and constipation. Talk to your health care provider about any side effect that bothers you or does not go away. These are not all the possible side effects of Victoza®. Does having to take it daily become more of a burden ? Those side effects are no different from every other GLP-1 analog. That is why I am skeptical that a TS delivered analog will be any different. The test MNKD did predated the availability of GLP-1 analogs and was only a single dose using GLP-1 rather than an analog.
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Post by agedhippie on Jun 9, 2023 10:03:02 GMT -5
If MNKD actually want to produce an inhaled GLP-1 then they can do it now. The patent on liraglutide (Victoza) expires this year and a generic is expected next year (at least two pharmas are lining up for this.) That will provide MNKD with a source of the API which they can then load onto TS.
Of course they will still need to prove that you can take it more than once and still have no side effects, and compare effectiveness to one of the GLP-1 analog with Victoza as the likely candidate. Then there is question of funding, nobody is going to touch it this side of the data from that phase 2 trial, and then the time to market because you don't want to launch and be a couple of generations behind the market (try selling human insulin today, it sells on price but it's a fraction of the RAA market)
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Post by agedhippie on Jun 9, 2023 9:28:58 GMT -5
Aged - I am not a chemist but I would think our team at MNKD can figure out how to load both of Pfizer's glp-1r molecules on technosphere. If not I think someone from RLS is still hanging around and may be able to do some consulting. Albert wouldn't get a pill but he would remove the needle. The funny thing is, a while back I had the opportunity to spend some time with the lead chemist on Exubera. He thought if it were not for afrezza, Exubera would have been a blockbuster. He had nothing but great things to say about afrezza. ... I wouldn't think it was difficult to load the Pfizer GLP-1 on TS, but that assumes Pfizer want to do that. My guess given the track record of inhaled insulin it's unlikely. Pfizer are focused on a pill (oral) which is what they already have. That lead chemist should revisit his timelines if he wants to blame Afrezza for Exubera's failure. Exubera was withdrawn in 2007, Afrezza didn't launch for another eight years in 2015. Exubera failed for several reasons, but the chief reason was they over-priced it so national health systems rejected it (higher cost for no tangible benefit), and US insurance cover was awful. Next up would be the bong and not using standard units (they used mg, why?) It's not something I ever used, but I know people who tried it. Everyone expects GLP-1 to come with GI issues, although GLP-1/GIP combinations have less so it's easier to accept those and rely on the pill as the driver. Last month 2.5M people were prepared to overlook the GI issues so there is a strong temptation to say why change. That's before we even address the issue of whether or not the GI issues go away if you use GLP-1 analogs. You are asking Pfizer to gamble against their own product, we saw with Sanofi how that ends.
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Post by agedhippie on Jun 8, 2023 21:31:10 GMT -5
No injections … better performance..avoids first pass hepatic metabolism.. less drug .. less I’ll feeling. dosing regime to be determined I agree on no injections, and am not sure why injected GLP-1 has a first pass hepatic metabolism but inhaled GLP-1 doesn't (genuinely, I don't know why they would differ). Everything else needs to be proven beyond a single shot of a GLP-1 (not GLP-1 analog like all the versions on the market) which is all the data we have at the moment.
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Post by agedhippie on Jun 8, 2023 17:49:16 GMT -5
Drugs like Danuglipron and Rybelsus are oral meds, they are pills. A TS GLP-1 would be an inhaled drug which is completely different class. No pharma is going to show interest this side of a Phase 2 trial because they want to be sure the side effects are really gone.
Pfizer would be a nice partner, but the question is if they have got over their last attempt to convert an injectable to inhaled (Exubera)
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Post by agedhippie on Jun 8, 2023 8:17:09 GMT -5
Hey - as I have said from the beginning when I say GLP1 I have been lumping Mounjaro in with that. If Doug is already ready to roll on a subq GLP1/GIP maybe putting that on TS provides the market advantage over Mounjaro. Maybe its gen 2.0 for him. It seems to have done wonders for Tyvaso. ... if Peter was right TS provides a real advantage. It also seems like right now MNKD is doing nothing. I sure hope that changes... Tyvaso was already an inhaled drug, Martine simply moved the inhaler from one inhaler to another. With GLP-1 Novo Nordisk would be moving from injected to inhaled which is a hard sell, not least because the only example of that is Afrezza which has not exactly been a resounding commercial success. From a marketing standpoint Novo Nordisk doesn't need an inhaler, they just need a competitive version and they can do the rest leveraging their relationships. The key word on TS-GLP1 is IF. Nobody knows how well it works beyond the fact that it doesn't kill you which is all a Phase 1 trial proves (also why Phase 1 trials are cheap and easy to do). There are a pile of unanswered questions; does it have side effects if you take it more than one, does it have side effects is you prolong the action (when the original work was done GLP-1 was a twice daily shot, now it's weekly so there is an expectation), how effective is it (more/less/same, as Mounjaro), will GLP-1 alone be sufficient or is GIP also needed as it seems that is more effective both for diabetes and weight loss? And the key question; how much money does Mike want to spend to roll the dice on those questions. I can see an announcement to help the share price, I don't see it ever coming to market because of the upfront costs.
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Post by agedhippie on Jun 7, 2023 22:47:51 GMT -5
Effectively yes. The added benefit is that GIP helps with nausea (they use it with some chemotherapy) as well as it's glucose management properties. Mounjaro will take over from Ozempic, but I suspect Novo Nordisk is already working on their version. I sounds like we all think Mounjaro is going to crush Ozempic and Wegovy sales. It sure seems like Novo Nordisk needs to be doing something. Why not Wegovy DPI? It sure seems UTHR has had great success with Tyvaso DPI. Maybe Doug Langa never considered it. Maybe he should. If the problem is Mounjaro then the issue is the GIP (Novo already have a GIP themselves in phase 2) so the answer is to develop that next gen drug and not focus on the last gen drug. Realistically Ozempic will hold market share for some time since currently they are constrained by their manufacturing and are selling everything they can make.
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Post by agedhippie on Jun 7, 2023 16:56:21 GMT -5
... stevil , Mounjaro packing a 1,2, punch? Effectively yes. The added benefit is that GIP helps with nausea (they use it with some chemotherapy) as well as it's glucose management properties. Mounjaro will take over from Ozempic, but I suspect Novo Nordisk is already working on their version.
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Post by agedhippie on Jun 6, 2023 21:29:55 GMT -5
... • pediatric patients aged 12 years and older with an initial BMI at the 95th percentile or greater for age and sex (obesity) (1).
... It looks like they already got the pediatrics label from that trial.
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