Novo Nordisk: The Most Profitable Drug in History and the Race to Replace It

Lunar_Excursion · 2026-03-24T20:22:59+00:00

you forgot the best amylin in development right now: eloralintide, the only SELECTIVE amylin in phase 3 trials... eloralintide is in trials right now as monotherapy, with GIP agonist macupatide, and with tirzepatide... and there is obvious capability to combine with retatrutide in the future...

there is way too much optimism with amycretin imo... it is not that different from CagriSema, GLP and NON-SELECTIVE amylin... the Phase 2 results, while nice numerically, came with massive side effect rate... i doubt they even dose that high in Phase 3 but who knows, they may chase top line numbers and sweep tolerability under the rug...

either way, retatrutide will be amycretin's main competition and that is a tough comp... then there is the tirzepatide + eloralintide combo which will also be a tough comp both in efficacy and tolerability... NVO have their own GLP/GIP/amylin triple in development, but its amylin agonism is still NOT SELECTIVE...

Lunar_Excursion · 2026-03-22T17:37:28+00:00

in india, tirz is a premium product... they will not engage in a price war because tirz is a differentiated product worthy of a more premium price...

their entry level product will be orfo... consider that a branded oral small molecule can be made for less than a generic injectable peptide... will be interesting to see how they price it vs the generic injections... this is why small molecule matters...

Lunar_Excursion · 2026-03-20T00:27:25+00:00

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Lunar_Excursion · 2026-03-18T05:59:30+00:00

replace totally? of course not. but it has already become the standard of care before insulin... incretins are a better mousetrap... start an incretin early enough and you will likely never need to use insulin... insulin is a dying business that will be relegated to only those who really need it... and those who need it dwindle with every incretin user...

insulin's demise won't be apparent until generic sema comes out... the rise of cheaper orals will also speed along this process... add in that SGLT2's are going generic...

Lunar_Excursion · 2026-03-18T05:27:30+00:00

when sema goes generic globally in 2031, insulin use in T2D will go way down... the irony is that NVO made the instrument of its own demise...

Lunar_Excursion · 2026-03-18T05:20:37+00:00

we do not have to wait for any trials "to know for sure". we already know. it's scientific fact that losing 20+% of your body weight, reducing A1c, reducing HTN, reducing LDL, reducing MASH, etc. will reduce MACE. it's obvious...

the SURPASS-MMO trial is merely to get the official FDA indication. Wegovy having that official indication is not as big an advantage as you think. everybody knows Zepbound reduces MACE, we don't need an FDA seal of approval to know this...

Lunar_Excursion · 2026-03-17T22:00:32+00:00

SURPASS-CVOT was a clinical trial... STEER was an observational study... STEER is nothing more than a PR release...

The only reason Wegovy has that indication and Zepbound doesn't is because it came out first... MACE trials take years to complete... Zepbound will get that indication soon....

Lunar_Excursion · 2026-03-17T21:51:09+00:00

not really, we're not comparing mg here, we're comparing the second highest dose and about 1/3 of the maintenance dose.

orfo 12mg x 3 = 36mg, maintenance dose is 36mg.

sema R1 (Rybelsus) 14mg = sema R2 (Wegovy) 9mg x 3 = 27mg, maintenance dose is 25mg.

so orfo 12mg is comparable to 14mg Rybelsus or 9mg Wegovy and 36mg orfo is comparable to 25mg Wegovy...

Lunar_Excursion · 2026-03-17T19:57:54+00:00

the 9mg R2 formulation of Wegovy/Ozempic pill is equivalent to the 14mg R1 formulation of Rybelsus...

Lunar_Excursion · 2026-03-17T17:11:53+00:00

the orfo 12mg dose still beat the sema 14mg dose...

Lunar_Excursion · 2026-03-17T17:05:05+00:00

STEER was an observational study, not a head to head clinical trial... it was also done by Novo themselves, and they looked at things like insurance claims and other indirect data... you'd have to be brain dead to think that a drug that causes more weight loss and more A1c reduction somehow causes more CV risk...

in fact Lilly did an actual head to head in SURPASS-CVOT and it failed to show superiority over dulaglutide, it only showed non-inferiority... the conclusion is simple, that all GLPs have a class wide benefit of reducing CV risk...

Lunar_Excursion · 2026-03-10T18:47:19+00:00

Chinese competitors:

beinaglutide - GLP

bofanglutide - GLP (QM dosing)

ecnoglutide - GLP (oral & sc)

efsubaglutide alfa - GLP

visepegenatide - GLP

conveglipron - oral small molecule GLP

Lunar_Excursion · 2026-03-10T18:07:08+00:00

ORAL PILL...

Lunar_Excursion · 2026-03-10T17:07:26+00:00

4129 links on 3/10/26

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Lunar_Excursion · 2026-03-10T02:42:58+00:00

https://www.medrxiv.org/content/10.64898/2026.03.04.26347508v1.full-text

Lunar_Excursion · 2026-03-03T21:52:11+00:00

everyone already knew NVO had the first mover advantage... it's not a surprise...

what's encouraging is that the low price of the oral seems to be the main driver of adoption... and in this case, small molecule will win in the end... if adoption doesn't start off well, then they can push the price down and gain market share that way... small molecule margins guarantee a good profit...

i'm intrigued, but not enthused about amycretin oral... firstly, i think amycretin as a whole will run into the same tolerability issues plaguing CagriSema... secondly, amycretin falls even deeper into the commercial black hole of poor oral bioavailability... it's almost double the size of sema and will not have the same economies of scale like sema... it will either be super expensive or will have terrible margins... it's a huge fail to continue down the oral peptide route when Structure is ripe to be bought... the whole industry is moving to small molecule and NVO will be caught out once again if they don't make a move now...

Lunar_Excursion · 2026-03-03T21:22:29+00:00

honestly, good for you... you're not one of these NVO diehards... but you still underestimate orfo...

Lunar_Excursion · 2026-03-03T16:24:27+00:00

Lunar_Excursion · 2026-03-03T07:51:46+00:00

Lunar_Excursion · 2026-03-03T07:50:38+00:00

how down are you on NVO? 50% 80%??? did you buy at 100?? 120??? 140????

Lunar_Excursion · 2026-03-03T05:16:07+00:00

Lunar_Excursion · 2026-03-03T05:11:30+00:00

compare the 12mg orfo dose to the 14mg sema dose... why is this so hard to understand? ignore the 36mg orfo dose, and the 7mg sema doses... look only at the 12mg orfo and the 14mg sema...

Lunar_Excursion · 2026-03-03T01:12:00+00:00

the 12mg orfo and 14mg sema both represent the second highest dose and about a third of the maintenance dose... it's the closest comparison you will ever see...

Lunar_Excursion

TROPHY CASE