Surprised there was no mention of the counterintelligence and economic espionage efforts emanating from the government of China and the Chinese Communist Party. They are a grave threat to the economic well-being and democratic values of the United States. Basically they steal everything that isn't nailed down including scientific research leading to results like these. They don't do it by developing or inventing anything on their own they take what was legitimately discovered herein the USA and make it their own. They then run unethical clinical trials that can harm or kill patients and amazingly those trials don't get glowing "advertisement" articles like this.
China is at war with us and has been for decades and articles like this do not help.
If you really, really think that it's very bad to use inventions from China, and perhaps we should make it easier to make those inventions here.
Which is pretty much the entire point that this author has been making everywhere she's been writing.
If you'd rather China not eat our lunch, perhaps we should not make it so hard to develop marvelously revolutionary treatments here rather than there, don't you think?
Cancer research here is painstakingly slow. Once you work in the field and have a loved one get it, you realize just how bad the situation is. Agree totally that it's not even about China. It's about benefiting humanity as a whole with better medicines.
Unethical it just different ethics? Desperate, tortured, dying patients can and should be allowed to volunteer for new drug trials. I would. Did you actually read here about the pain of myeloma and the conventional treatments?
I don’t see any evidence in this article that the Carvykti story is different from a bog standard fast follower development story
I’m sure it’s true that there are less regulatory hurdles to doing clinical trials in China but fast follower/me too tech dev is a thing in the US as well, and it has well known advantages in terms of speed of development! Keytruda began development after Opdivo, and was basically a dead project until Merck saw Bristol-Myers Squibbs’ Opdivo data, but they managed to get approval basically simultaneously w/ Opdivo. And in that case, as with many other “me-too” drugs, the me-too drug was significantly better. Funny that the loser in both cases was BMS...
What leads you to think that Chinese regulatory speedups were the key for Carvykti?
I think the story illustrates that they're fast (through timeline) and that they are actually making rly good drugs. Being fast and cheap allows them to do many of these trials and obvsly get some good hits on the way and they have gotten ahead in the number of cell therapy trials. They are also increasingly close in terms of first-in-class.
I don't know how you prove that one individual therapy specifically was better because of speed, but high speed and low costs have created a system where it's easy to do IITs and the overall stats show that they're pulling ahead in terms of actual results.
I guess also to add: if you look at Phase I timelines, they are actually very fast. I don't think an American company could have done a me too do fast. Certainly they couldn't do it now.
I think it's to a non-trivial degree because of IITs, at least in cell therapy. Manufacturing requirements for complex biologics for Phase I are such that it is extremely expensive and slow to test anything in the US. Slow also means expensive in biotech, due to burn rate at the clinical stage. We are curing cancer, but VC funding in early-stage biotech for cell therapy has fallen a lot since 2021. Instead, these are licensed from China.
Terrific piece — the Carvykti/Legend story is the perfect lens. The sequel's already forming: that same Legend now has LB2501, an in vivo CAR-T that just showed responses in 6 patients. If it holds, the manufacturing bottleneck you describe doesn't just shrink — it potentially disappears. I mapped that "what replaces the cell factory" question across Kite, Lilly/Kelonia and AbbVie/Capstan here: https://novc.substack.com/p/what-replaces-yescarta?r=6p7sjb
OT: The drug costs roughly $500k. There has been plenty of discussion about the price of CAR-T therapies, but much less about who captures that value. Hint: the scientists who made the breakthroughs possible receive only a small fraction of it, and those doing the most fundamental research often receive the least. That should bother us also.
One of the greatest advantages China has is a large population of dissidents upon which to perform any sort of medical experiments they wish. I can't help thinking that might give them certain advantages in drug development. Fortunately, the current administration in America seems to be posessed of a highly deregulatory spirit, so hopefully medical research will accelerate accordingly.
One thing I'd like to know more about, perhaps from this blog, is an explanation of allegations we've been hearing for so many years: That the US govt funds pharmaceutical research, but never gets paid back [much less profit-sharing] by pharma companies who develop successful patents. Is this true, and why? I kinda suspect there might be more nuance to such a seemingly lopsided arrangement, but I'm too busy to investigate.
I understand that rapid vaccine development can be a risky proposition for manufacturers, so I get why that might be subsidized. But I don't get why any major subsidy to any industry does not have some public profit-sharing conditions, or at least a pre-arranged agreement to keep domestic drug prices capped in exchange for funding.
Then again, a lot of that funding wouldn't even be necessary if the FDA would merely return to the original mandate of safety testing, rather than the current mandate of efficacy testing, which is obviously a moat for pharma incumbents, but does not result in the advertised benefits, nor the avoidance of expensive but minimally effective drugs coming to the market.
I often wonder when the hoi polloi will seize upon the notion that excessive safetyism dissuades innovation, and that it's not economically feasible to have everything we want at the same time. I suppose the answer is "When all attempts at achieving impossible outcomes become unsustainable."
I'm not an expert, but I know a few things about this. The notion that development is being paid for by the government and pharmaceutical companies are free riding is appealing, but the vast majority of the spend is in the late stage clinical trials, which is what the pharmaceutical companies pay for.
In terms of what you can really accomplish by bypassing ethics, I don't think you very much by being evil. Maybe you can do challenge trials for infectious disease treatments (mainly vaccines), but that's about it, right?
Thanks for clearing that up. For years I've been hearing that pharma companies are free riding, both on govt and private university grants, but that sounded suspicious to me. Although the healthcare sector has such an unholy alliance with politicians that nothing would surprise me anymore.
I was being sarcastic about China, but they obviously have a unique pool of available transplant organs from being evil. Not that I recommend that. But I do recommend going back to more basic safety testing ONLY for new drugs, because that's difficult enough, and efficacy testing dramatically increases development time and expenses for marginal benefits. And I agree with you about challenge trials; not only for time sensitive cases like pandemic vaccines, but also for any drug that might help patients who have nothing to lose. I think people with a terminal diagnosis should be able to participate in any trial they want, if the mfr can make use of their data.
This is what killed blogger Kevin Drum a few years ago, having had it for over a decade.
This is possibly a bit silly, but is there a reason why the standard of care groups in the two trials don't seem comparable?
That's not a silly question at all! I need to check actually.
Surprised there was no mention of the counterintelligence and economic espionage efforts emanating from the government of China and the Chinese Communist Party. They are a grave threat to the economic well-being and democratic values of the United States. Basically they steal everything that isn't nailed down including scientific research leading to results like these. They don't do it by developing or inventing anything on their own they take what was legitimately discovered herein the USA and make it their own. They then run unethical clinical trials that can harm or kill patients and amazingly those trials don't get glowing "advertisement" articles like this.
China is at war with us and has been for decades and articles like this do not help.
When their mom gets leukemia, people tend to not care what country the therapy designer and manufacturer is from.
If you really, really think that it's very bad to use inventions from China, and perhaps we should make it easier to make those inventions here.
Which is pretty much the entire point that this author has been making everywhere she's been writing.
If you'd rather China not eat our lunch, perhaps we should not make it so hard to develop marvelously revolutionary treatments here rather than there, don't you think?
Cancer research here is painstakingly slow. Once you work in the field and have a loved one get it, you realize just how bad the situation is. Agree totally that it's not even about China. It's about benefiting humanity as a whole with better medicines.
Unethical it just different ethics? Desperate, tortured, dying patients can and should be allowed to volunteer for new drug trials. I would. Did you actually read here about the pain of myeloma and the conventional treatments?
https://www.fbi.gov/investigate/counterintelligence/the-china-threat
I don’t see any evidence in this article that the Carvykti story is different from a bog standard fast follower development story
I’m sure it’s true that there are less regulatory hurdles to doing clinical trials in China but fast follower/me too tech dev is a thing in the US as well, and it has well known advantages in terms of speed of development! Keytruda began development after Opdivo, and was basically a dead project until Merck saw Bristol-Myers Squibbs’ Opdivo data, but they managed to get approval basically simultaneously w/ Opdivo. And in that case, as with many other “me-too” drugs, the me-too drug was significantly better. Funny that the loser in both cases was BMS...
What leads you to think that Chinese regulatory speedups were the key for Carvykti?
I think the story illustrates that they're fast (through timeline) and that they are actually making rly good drugs. Being fast and cheap allows them to do many of these trials and obvsly get some good hits on the way and they have gotten ahead in the number of cell therapy trials. They are also increasingly close in terms of first-in-class.
I don't know how you prove that one individual therapy specifically was better because of speed, but high speed and low costs have created a system where it's easy to do IITs and the overall stats show that they're pulling ahead in terms of actual results.
I guess also to add: if you look at Phase I timelines, they are actually very fast. I don't think an American company could have done a me too do fast. Certainly they couldn't do it now.
That's fair. Agree that it's clear that they're making good drugs.
I would say it's more than this.
I think it's to a non-trivial degree because of IITs, at least in cell therapy. Manufacturing requirements for complex biologics for Phase I are such that it is extremely expensive and slow to test anything in the US. Slow also means expensive in biotech, due to burn rate at the clinical stage. We are curing cancer, but VC funding in early-stage biotech for cell therapy has fallen a lot since 2021. Instead, these are licensed from China.
It would be interesting to see the numbers on that, as well as the stats on China pulling ahead in actual results.
sorry this didn't send from my laptop will send soon
As long as we demonize those who think or live differently from us, we will fail to come anywhere close to objectivity—or love.
Terrific piece — the Carvykti/Legend story is the perfect lens. The sequel's already forming: that same Legend now has LB2501, an in vivo CAR-T that just showed responses in 6 patients. If it holds, the manufacturing bottleneck you describe doesn't just shrink — it potentially disappears. I mapped that "what replaces the cell factory" question across Kite, Lilly/Kelonia and AbbVie/Capstan here: https://novc.substack.com/p/what-replaces-yescarta?r=6p7sjb
OT: The drug costs roughly $500k. There has been plenty of discussion about the price of CAR-T therapies, but much less about who captures that value. Hint: the scientists who made the breakthroughs possible receive only a small fraction of it, and those doing the most fundamental research often receive the least. That should bother us also.
✅💯 excellent discussion 💯
One of the greatest advantages China has is a large population of dissidents upon which to perform any sort of medical experiments they wish. I can't help thinking that might give them certain advantages in drug development. Fortunately, the current administration in America seems to be posessed of a highly deregulatory spirit, so hopefully medical research will accelerate accordingly.
One thing I'd like to know more about, perhaps from this blog, is an explanation of allegations we've been hearing for so many years: That the US govt funds pharmaceutical research, but never gets paid back [much less profit-sharing] by pharma companies who develop successful patents. Is this true, and why? I kinda suspect there might be more nuance to such a seemingly lopsided arrangement, but I'm too busy to investigate.
I understand that rapid vaccine development can be a risky proposition for manufacturers, so I get why that might be subsidized. But I don't get why any major subsidy to any industry does not have some public profit-sharing conditions, or at least a pre-arranged agreement to keep domestic drug prices capped in exchange for funding.
Then again, a lot of that funding wouldn't even be necessary if the FDA would merely return to the original mandate of safety testing, rather than the current mandate of efficacy testing, which is obviously a moat for pharma incumbents, but does not result in the advertised benefits, nor the avoidance of expensive but minimally effective drugs coming to the market.
I often wonder when the hoi polloi will seize upon the notion that excessive safetyism dissuades innovation, and that it's not economically feasible to have everything we want at the same time. I suppose the answer is "When all attempts at achieving impossible outcomes become unsustainable."
I'm not an expert, but I know a few things about this. The notion that development is being paid for by the government and pharmaceutical companies are free riding is appealing, but the vast majority of the spend is in the late stage clinical trials, which is what the pharmaceutical companies pay for.
In terms of what you can really accomplish by bypassing ethics, I don't think you very much by being evil. Maybe you can do challenge trials for infectious disease treatments (mainly vaccines), but that's about it, right?
Thanks for clearing that up. For years I've been hearing that pharma companies are free riding, both on govt and private university grants, but that sounded suspicious to me. Although the healthcare sector has such an unholy alliance with politicians that nothing would surprise me anymore.
I was being sarcastic about China, but they obviously have a unique pool of available transplant organs from being evil. Not that I recommend that. But I do recommend going back to more basic safety testing ONLY for new drugs, because that's difficult enough, and efficacy testing dramatically increases development time and expenses for marginal benefits. And I agree with you about challenge trials; not only for time sensitive cases like pandemic vaccines, but also for any drug that might help patients who have nothing to lose. I think people with a terminal diagnosis should be able to participate in any trial they want, if the mfr can make use of their data.
Why no mention of T cell engagers e.g teclistamab? The data for them is at least as impressive as CAR-T.