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RVNC
Oh, and I forgot an obvious prediction: that there will be many fewer approvals for Follow On Indications. For many drugs this doesn’t matter much, but for some it’s a huge factor. Oncology, TNF drugs, CD19 targeting drugs, … .
This is a much better piece than similar pieces I’ve seen on other mainstream media. Eg it gives real examples (one I’ve actually experienced - I had to go to Costco to actually get generic price. My local RiteAid wanted to charge me 10x that. Interestingly the pharmacist at RiteAid clearly knew something unethical was happening, even knew the conditions of it - but had also been clearly warned not to talk about it.).
Topol:
People are simply not going to pay a premium for something that lasts 3-4 weeks longer.
I lean pessimist by design, and I’ve seen nothing to indicate it lasts only 3 or 4 weeks longer when used properly.
Of course the fly in the ointment is that the company provided no guidance on how to use it well in a large muscle like frontalis and it looks like injectors were using it like they did Botox (ie incorrectly for Daxxi).
Now the problem is they have to convince people to retry it after having been, as far as the injectors and patients are concerned, burned. Ideally after they can subtley point to ‘best practice’ for frontalis.
Hopefully they don’t repeat the same error with therapeutics and non-CD indications.
That implies the under treatment of HIV should be an addressable priority irrespective of the virus mutations in normal populations.
Sure, but it’s cultural and state capacity problem. Other countries in Africa have similar population of HIV infected. They do reasonably well treating them. But S. Africa has big governance and related cultural problems.
New COVID jump mutation strain. Predict: 50/50 chance that if it takes, it takes off first in S. Africa.
Basis of predict:
A) S. Africa has been origin for two of the previous big jump strains of COVID. Almost certainly because they have, by far, the biggest population of under-treated HIV patients, which is like boot camp for COVID evolution.
B) after the last one of these events, S. Africa felt burned by international reaction including both noticing the above and then stopping travel to/from S. Africa. So they talked about being less open.
Practice locator showed about 850 at end of June. Now showing 720-730ish if my eyes aren’t deceiving me
The latter number is approximately correct (ie what the Revance site says). No idea what is said at end of June. But not sure how to mesh these website numbers with the 'greater than 6000 accounts' mentioned for end of Q2 (from the recent cc). It implies either the Practice Locator is not kept current for some reason, or the way accounts are measured is very different than practices.
Notes:
a) RHA Provider Practices' websites only mention RHA about half the time, although they almost always mention at least one specific filler (eg Juvederm)
b) Daxxi Provider Practices' websites appear to mention Daxxi specifically much more often (altho amusingly sometimes under the tab/section labelled Botox), altho I'd need to do a larger sample to be sure.
c) Based upon a small sampling, the overlap of the RHA Providers and Daxxi Provers from the Revance site is about 1/4 of all the unique providers listed in the two databases.(so I'd estimate the total number of unique providers on their website is about 1250) That amount of overlap seems surprisingly low, but I found only one instance where a provider listed on only one of the lists claimed to have both Daxxi and RHA. (But note again... smallish sample)
are you reconstituting with 1.25cc bacteriostatic saline? same push volume as Botox?
are you injecting 2 units daxxify to 1 unit botox?
are you spreading the Daxxify units by injecting 2 rows across frontalis instead of just one row? the daxxify appears to not migrate as far as botox and therefore not seeing migration from glabella up to lower frontalis. Guessing the peptide may be responsible for its localized stickiness to the nerve terminal and minimal spread. Also not seeing it diffuse down frontalis when placed too high in a single row.
Question: what are the typical methods by which this kind of information is disseminated in aesthetics treatment? Conferences/posters? Papers? Web boards?
I ask because in other areas of medicine it generally isn't great - but at least some practitioners go to conferences?
My tip to you would be 2 to 2.4x Daxi units to 1 unit of Botox that you typically do for frontalis and 1.8 units of Daxi to every 1 unit you use in the Glabella (not 2x). Spread the daxi into 4 to 6 injection points across 2 horizontal rows across frontalis with each point getting 2 units of Daxi = 20 to 24 units total daxi in frontalis.
Well, that was a good, detailed post of the kind that is EXTREMELY hard to get from the literature. And aligns with everything you'd expect (2x "Units" vs Botox, less spread).
Q: If I can... what is the most common AE from frontalis treatment?
The difference between the actual (relative) MACE reduction of 20% and my estimate of 15% is highly consequential from a commercial standpoint, IMO.
Good bet that if they let the trial run longer is would be meaningfully better than the 20% number:
a) In T2D the curves don't separate until 12 to 18 months, and there will be more events in that part of the curve
b) The weight loss, and it's effects on Metabolic Syndrome markers, is huge and you'd expect it to have a bigger effect.
My bet: if you measure the slopes of the KM curve starting at 15 months... the 'HR' will be less than 0.7. (Note that I put HR in scare quotes because this isn't an accepted way of talking about HR, but it is, nonetheless, correct. (Lots of things in formal stats are rigid by design, but only to prevent humans from gaming data))
Yes, boraborak38 is most likely an ABBV shill based on their most recent posts. Dubious that such an incompetent injector could stay in business.
Suggest everything works better if you don’t always accuse everyone with a different opinions of being intentionally dishonest.
Take a look at what happened to xeomin years ago. They were not allowed to market in US for 1 year.
Are you referring to Xeomin injunction (for 10 months) due a lawsuit by Allergan claiming theft of trade secrets?
https://www.consultingroom.com/blog/allergan-wins-legal-battle-to-stop-sales-of-botox-rival-xeomin-by-merz
If so… that wasn’t about Merz providing guidance for off-label indications. So I’m still somewhat curious about recent history of FDA regulatory actions regarding off-label usage. (FDA lost pretty big 5 or 6 years ago, but am not sure what current case law and history is)
Question I have is, is the poor launch you've sensed and experienced something the company could control had they been more prepared or marketed differently, or was it more about how hard it is to break into an entrenched cosmetic toxin market in general?
One thing I had not appreciated is how word-of-mouth and patient specific treatment practice is. The combination, in off-label particularly, would almost certainly slow uptake, particularly switching. Eg in the post below the md notes it took 5 runs to get dosing right in his CD patient. Seems likely that’s more diligence than normal (that’s more than a year of keeping track of what worked and what didn’t the last times), but even if a more typical usage is tuning for 2 or 3 times, … that’s a big impediment to switching. And altho aesthetics almost certainly has less patient specific diligence, it seems likely there is at least some patient specific tuning that will impede switching.
Finally, I hadn’t appreciated how difficult it wld be for Revance to coordinate lessons for off label use - eg optimal dilution or injections sites for larger muscles? But all that said, the difference in efficacy is large enough that *eventually* …
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=172523514
Dosing outside glabellar lines:
They were asked about how messaging changed based upon learnings from prevue rollout. And they said:
"Their experience in different areas on the dosing side as well. We did find that some of these early practices, just out of conservatism, were dosing at a level that was delivering less than the amount of neurotoxin that would be given with a competitor"
This was likely a reference to non-Glabellar lines dosing (i.e. 'different areas', dosing is compared to competitor, not label) - although in a later summary attention is reflexively drawn back to glabellar lines.
My assumption is they do not want to weigh in on off-label treatment.
…about 10% of NASH patients are actually skinny.
According to VKTX’s CEO on today’s CC, these patients are primarily Asian.
ALDH2-2 related? https://mdpi-res.com/d_attachment/biology/biology-10-00737/article_deploy/biology-10-00737.pdf?version=1627813541
Lab Leaker vs Zoonoti
Now that Andersen’s Slack channel has been subpoenaed and become public there is ZERO dispute that, as I noted before, the zoonoti enforcing the narrative “Lab Leak is a conspiracy theory” actually believed the inverse in varying degrees. Even long after they had published a paper saying the opposite and had been trying to taint people on social media. The below link is a good summary of quotes from the slack channel.
Good summary list of quotes from scientists who were the nucleus enforcing the narrative that “lab leak is a conspiracy theory”.
— Clark H (@Clarksterh) July 23, 2023
Comment: there are other comments in Slack, from them, that make it clear their concern was LL wld tarnish virology (to put it mildly) https://t.co/NJVxoxZze2
That doesn't explain why the price of Humira increased from around $1000 per month to over $7000 in twenty years. As they added numerous indications the volume should have pushed the price down
I did not, in any way, defend Pharma pricing per se. Nor did I try to justify removal of 13 year limit. My sole point was that the 13 yr vs 9 yr differences was/is pretty unambiguously bad (ie will cost US more money than equal split or reversed split) and happened for inane and innumerate reasons.
If you want to change the subject to Pharma misbehaving… happy to do so. There are plenty of instances. But because the Sanders crowd, which is the primary anti-Pharma mover, is innumerate they often lump in lots of behavior that has little to do with pharma (eg PBM misbehavior), so care needs to be taken to separate that out.
why the IRA gives biologics 13 years and small molecules only 9 is bizarre and makes for really bad legislation.
This happened, literally, because the activists and lawmakers are wildly more concerned with profit margins than patient costs (see below for bullets for explanation and why this is remarkably stupid). It’s the Bernie Sanders wing and his voters - who seethe about drug companies for all sorts of incoherent reasons. Happens even with people who are otherwise moderately rational - eg every ill (like current trans social contagion in HS) is blamed on drug companies.
1) Biologics generally have lower *margins* because manufacturing is much more expensive than for small molecules.
2) but total cost for biologics, even when on patent, is higher than for small molecules. Companies, sensibly, want to make same absolute profit, even on top of larger manufacturing costs.
3) where it gets remarkably stupid is that substitutable generics, which will bring down costs *much* more than IRA negotiations, are very very difficult for biologics. But the IRA immensely incentivizes biologics anyway. Perfect lose lose for everyone involved.
RVNC
Mgt isn’t being particularly forthcoming about specifics. And in a new launch, where only some of the usage in the trial’d application (what percent of Botox used for aesthetics is outside glabellar lines - eg frontalis), where different providers ‘tune’ their protocols, lack of specifics matters.
Hopefully they are a little more transparent and intentional internally and with providers - but history with other biotech says that’s not the norm. External appearance of blowing in the breeze is normally just a reflection of internal lack of crisp direction.
That said, the excess benefit over previous SOC that I’d expect that, moderately rapidly, the providers will figure it out anyway.
Fastox - FTP-501
A lot of uncertainty.
A) they’ve released minimal data, even of animal models.
B) what they have released (one graph of mouse DAS?) is interesting, but shows only about 65% more duration to their own benchmark of DAS=2. Much less percent advantage, given their linear decay curve, to a lower point on curve. And even to their chosen point of decay… about the same proportionate duration benefit that Daxxy has exhibited in clinical trials.
C) the linear decay curve for DAS looks… odd. It’s not what I’d expect in decay curves and not what is seen on other DAS curves.
D) and, of course, this DAS model data doesn’t give any way to understand what the AE effects were.
Finally, they seem to run a little slow vs their stated timelines. Mid 2022 they were touting entering clinical trials starting early 2023, but now it’s ‘by end of 2023’.
All told… interesting to watch. But not yet even a remote threat.
It might be okay for weight loss because many patients will only use the medications for a modest time period then come off once they have lost a target amount of weight
There is a reasonably strong rebound effect upon discontinuation, altho not all the way back to baseline (it seems to start asymptoting at perhaps, ~30% of best weight loss):
Lots of concern about #weight regain after stopping a med like #ozempic https://t.co/nT9sneLdJP
— Beverly G. Tchang, MD (@BevTchangMD) January 31, 2023
Great study cited by @people : https://t.co/jpQPGYo5tr shows what happened in STEP1 extension
Weight seems to go back to baseline. But not worse. There’s no excess rebound effect. pic.twitter.com/aIuoFjILeC
The subject (under-dosing, especially frontalis) came up briefly on the Blair webcast two days ago.
Perhaps I missed it (was doing chores at time), but all I heard was a 1 or 2 sentence description of using this startup period to feed results from early adopters into training for later adopters. ? Nothing specific to frontalis, which is, as best I can tell, the biggest/most-cared-about-by-users(?) uncertainty.
I wonder if patients do daxi for 1-2 injections then change back to Botox they may think differently upon the daxi experience. Oh wait it actually did last longer..
Agree this is likely to happen, especially since there was way too much emphasis on 2x as long. (Revance didn’t directly push this, but certainly enabled it - and exaggerating claims creates disappointment)
But also suggest there was likely significant underdosing for forehead in first round. Hopefully fixed now? But need confirmation of that - and not clear whether Revance can speak directly to this since, strictly speaking, it’s outside label.
Valley of death to Precision Drugs:
Delayed response to figure out how to communicate diff of opinion:
— Clark H (@Clarksterh) May 19, 2023
Suggest the problem is there is a Valley of Death btwn where we are now (ethnic subgroups, v poor GRS) and full GRS for both risk and treatment. 1/n
As of this instant she’s gotten about 3000 views and you’ve gotten about 1400. That doesn’t seem completely out of line?
If you, or she, had gotten more likes, the liked tweet would likely have been boosted. But the rate of likes was quite low for both. (Typical is 1%, but both you and she got about 1/7th of that)
FWIW - I think my biotech tweets generally get fewer likes than my other commentary? More niche, and biotech community has higher standards?
RETA - credit where credit is due.
Statins - FWIW some of the statins are quite different. Eg Pitavastatin.
It will have *some* of the same side effects but not others.