3 ms·

Most of the cost is regulatory. But there is a meaningful difference between a world in which it costs $1M to screen and a world in which it costs $100k to scre

Most of the cost is regulatory. But there is a meaningful difference between a world in which it costs $1M to screen and a world in which it costs $100k to screen. In the latter world, startups become viable with intent to find a drug candidate, rather than only being viable if they already have one. That's a big important difference, and one that was only otherwise going to be solved by everyone transitioning from small molecule to gene therapy development.

vapemaster 8y ago
interesting point. though this ignores the (surprisingly) successful re-purposing strategies to reduce future regulatory burden and and reduce or even eliminate high throughput screening campaigns. that well will dry up sooner or later but other discovery platforms ie phage display etc. have become commoditized and robust enough that they are pretty accessible to even low capitalized startups if finding a ligand is what you need to get off the ground.
HarryHirsch 8y ago
The real cost occurs in Phase 2 clinical trials, where 70 % of promising-looking compounds turn out to be no better than placebo. The body is a complex system with a huge number of enzymes and feedback circuits, this outcome isn't much of a surprise then. You can't blame the FDA. But thanks to Trump's "right-to-try" phase 2 will be a smaller hurdle now. Good luck, let's see how costs develop.
- randcraw 8y ago
  No. Phase 3 is where all the cost of clinical trials comes from, not phase 2. P2 usually involves fewer than 100 patients and lasts for only a few months; P3 often runs to thousands of patients and can last for years, and then can be followed by supplementary P3 and even P4 trials, multiplying costs further. Phase 2 rises to a high fraction of clinical trial cost only in diseases with a very high mortality rate, like cancer. Then the drug may undergo a variant of P2/P3 trial where the general patient populace serves as early P3 trial participants, thereby reducing P3 trial cost normally paid entirely by the drug manufacturer. But even then, such a phase 3 trial will greatly outcost any phase 2, and will much more definitively answer the questions of drug safety and efficacy. The rules of those kinds of clinical trials (mostly cancer) where the "right-to-try" law is applicable thus will depart considerably from standard drug safety standards for almost all other kinds of drugs. That's because safety concerns are strongly deemphasized when investigating new cancer treatments due to 1) the high toxicity of alternative cancer therapies (usu. chemo), 2) the low survival rate and lifetime typical of most cancers, and 3) the lack of better alternative treatments. The lower standard for efficacy (and lower statistical power) inherent in phase 2 trials will certainly play a greater role in "right-to-try" than is usual for typical drugs. But this does NOT imply that taking the greater risks that will arise with these more speculative unproven therapies (like the Laetrile dud cancer therapy ca. 1975) are likely to return greater rewards. In all likelihood, by the time "right-to-try" comes into play for a patient, all hope will have been lost medically. Thus the fraction of cases where a patient will actually benefit from such a "hail Mary" therapy that's been facilitated via this law is essentially zero. Nor is the lack of methodical treatment regimen endemic to these still half-assed therapies likely to teach us much in the process of calling upon them just one second before midnight. No, "right-to-try" seems mostly an invitation for charlatans to charge megabucks for nutty therapies that have shown no level of success. If they had, "right-to-try" wouldn't have been needed. The era of hoping for a magic elixir is over, except in Hollywood and Trump's Washington, that is.
aaavl2821 8y ago
You can do a screen with a CRO for low six figures

vapemaster 8y ago

interesting point. though this ignores the (surprisingly) successful re-purposing strategies to reduce future regulatory burden and and reduce or even eliminate high throughput screening campaigns. that well will dry up sooner or later but other discovery platforms ie phage display etc. have become commoditized and robust enough that they are pretty accessible to even low capitalized startups if finding a ligand is what you need to get off the ground.

HarryHirsch 8y ago

The real cost occurs in Phase 2 clinical trials, where 70 % of promising-looking compounds turn out to be no better than placebo. The body is a complex system with a huge number of enzymes and feedback circuits, this outcome isn't much of a surprise then. You can't blame the FDA. But thanks to Trump's "right-to-try" phase 2 will be a smaller hurdle now. Good luck, let's see how costs develop.

randcraw 8y ago
No. Phase 3 is where all the cost of clinical trials comes from, not phase 2. P2 usually involves fewer than 100 patients and lasts for only a few months; P3 often runs to thousands of patients and can last for years, and then can be followed by supplementary P3 and even P4 trials, multiplying costs further. Phase 2 rises to a high fraction of clinical trial cost only in diseases with a very high mortality rate, like cancer. Then the drug may undergo a variant of P2/P3 trial where the general patient populace serves as early P3 trial participants, thereby reducing P3 trial cost normally paid entirely by the drug manufacturer. But even then, such a phase 3 trial will greatly outcost any phase 2, and will much more definitively answer the questions of drug safety and efficacy. The rules of those kinds of clinical trials (mostly cancer) where the "right-to-try" law is applicable thus will depart considerably from standard drug safety standards for almost all other kinds of drugs. That's because safety concerns are strongly deemphasized when investigating new cancer treatments due to 1) the high toxicity of alternative cancer therapies (usu. chemo), 2) the low survival rate and lifetime typical of most cancers, and 3) the lack of better alternative treatments. The lower standard for efficacy (and lower statistical power) inherent in phase 2 trials will certainly play a greater role in "right-to-try" than is usual for typical drugs. But this does NOT imply that taking the greater risks that will arise with these more speculative unproven therapies (like the Laetrile dud cancer therapy ca. 1975) are likely to return greater rewards. In all likelihood, by the time "right-to-try" comes into play for a patient, all hope will have been lost medically. Thus the fraction of cases where a patient will actually benefit from such a "hail Mary" therapy that's been facilitated via this law is essentially zero. Nor is the lack of methodical treatment regimen endemic to these still half-assed therapies likely to teach us much in the process of calling upon them just one second before midnight. No, "right-to-try" seems mostly an invitation for charlatans to charge megabucks for nutty therapies that have shown no level of success. If they had, "right-to-try" wouldn't have been needed. The era of hoping for a magic elixir is over, except in Hollywood and Trump's Washington, that is.

aaavl2821 8y ago

You can do a screen with a CRO for low six figures