Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

Clinical failure rates over the decades: yikes

science.org

Post reply on HN
Print view View original

101–110 of 146 posts

Re: Clinical failure rates over the decades: yikes

#101

Post by pama »

pinkmuffinere wrote: post #56

> But let’s think about that 91% failure rate for a moment. When I bring this up in presentations, I invite the audience to consider what the auto industry would look like of 91% of new car designs proved unable to roll out of the factory, or if 91% of new airliner models were unable to leave the ground - and if you only found that out after spending all the R&D money to build them at full size and trying to fly them…

The drug candidates that enter human clinical trials, (phase 1 to phase 3) are identical in all ways to the final product if approved. The company is not allowed to change any part of the manufacturing process. All the research for how to make the drug is done in preclinical phases. In the clinical phase we test the unknown human biology with a final product candidate.

Re: Clinical failure rates over the decades: yikes

#102

Post by bonsai_spool »

refurb wrote: post #98
bonsai_spool wrote: post #78

Earlier quoted context omitted.

This is very facile thinking - are there any examples of a-e in the real world (namely, a brand new drug program was spun up to exploit a-e) ? I think not, which is why I asked the question.

Look at the GLP-1s. Lilly spent tens hundreds of millions developing an oral version that was otherwise the same as the injectable’s. And the notorious inhaled insulin that Pfizer launch (and horribly failed). There are many ways to differentiate drugs, not just efficacy.

You are correct. I disagree with alternatives being better as a rule but these are clearly areas where there's a market (to wit, people don't like injecting themselves and prefer pills).

Re: Clinical failure rates over the decades: yikes

#103

Post by ip26 »

pinkmuffinere wrote: post #56

> But let’s think about that 91% failure rate for a moment. When I bring this up in presentations, I invite the audience to consider what the auto industry would look like of 91% of new car designs proved unable to roll out of the factory, or if 91% of new airliner models were unable to leave the ground - and if you only found that out after spending all the R&D money to build them at full size and trying to fly them…

Phase 3 seems closer to doing a soft production launch and finding customers completely reject it despite early focus groups liking it.

Prototypes, when they fail, are also often tweaked into something that works. A lot of phase 3 failures appear to have been complete dead-ends.

Re: Clinical failure rates over the decades: yikes

#104

Post by ip26 »

a_bonobo wrote: post #26
levocardia wrote: post #3

I'm actually surprised it isn't going up over time. That is naively what you would expect as the low-hanging fruit is plucked. So the fact that it's been stable is probably a sign that scientific advances are roughly keeping pace with the (presumably) increasing challenge of finding ever more targets for drugs.

I actually do this for a living within pharma now! There's a TON of work that goes into drug discovery before we even call it a program. The odds of success are low, so we put in months of work evaluating a candidate before even have a hunch of a program. Yes, the science advances, previously high-hanging fruits become low-hanging become high-hanging again [1], but the tooling also advances: we now have databases lik…

Is public perception the greater problem, or delivery? My outsider read has been relatively few diseases can be targeted right now due to payload delivery obstacles

Re: Clinical failure rates over the decades: yikes

#105

Post by bonsai_spool »

s1artibartfast wrote: post #95
bonsai_spool wrote: post #62

Earlier quoted context omitted.

That isn’t how a rational person would pursue this - it costs $1B to make a drug start to finish, and there’s no reason to believe your new mechanism will work. If you’re talking about copycat mechanisms, that is fine but we’re still left discussing successes when OP is about failures

Why isnt it rational? You spend the 1 billion for a ticket to win 30 billion/yr for the next several years. Is it rational to spend 1$ to make $100 10% of the time? A 99% failure rate would be break even.

> Why isnt it rational?

You can spend that $1B to win a new category or that same money to maybe be non-inferior to Keytruda, but maybe fail. I think copycat design does happen, but I mostly notice it when drugs are being developed simultaneously at different firms. Perhaps it happens more beyond this, I'm unsure.

Otherwise, it makes more sense to try to find an indication where you are approved and have no competition.

Re: Clinical failure rates over the decades: yikes

#106

Post by nradov »

bonsai_spool wrote: post #78
inglor_cz wrote: post #76

Earlier quoted context omitted.

"Why would anyone make a drug if the current prevalent treatment was as good as a functional cure?" I am not sure whether you ask for economic why, or an overall why. The overall why seems easier to explain: a. The new drug may be cheaper. b. The new drug may be safer. (e.g. no risk of anaphylaxis etc.) c. The new drug may not need cold storage (huge problem outside the First World). d. The new drug may have other pr…

This is very facile thinking - are there any examples of a-e in the real world (namely, a brand new drug program was spun up to exploit a-e) ? I think not, which is why I asked the question.

What an ignorant comment. Are you not familiar with Mavyret, Vosevi, or Xatmep?

Re: Clinical failure rates over the decades: yikes

#107

Post by s1artibartfast »

bonsai_spool wrote: post #78
inglor_cz wrote: post #76

Earlier quoted context omitted.

"Why would anyone make a drug if the current prevalent treatment was as good as a functional cure?" I am not sure whether you ask for economic why, or an overall why. The overall why seems easier to explain: a. The new drug may be cheaper. b. The new drug may be safer. (e.g. no risk of anaphylaxis etc.) c. The new drug may not need cold storage (huge problem outside the First World). d. The new drug may have other pr…

This is very facile thinking - are there any examples of a-e in the real world (namely, a brand new drug program was spun up to exploit a-e) ? I think not, which is why I asked the question.

I dont know why you are being rude about a topic you know nothing about. As some who actually does this for a career, they are largely correct. Dose frequency and side effects especially are major reasons. I would add route of administration and patient convenience as well.

Anti-vegf treatments for blindness are a good example if you want to research. They all have basicly the same effect in terms of letters preserved on an eye chart if dosed as perscribled.

It's a 15 billion dollar per year Market that resolves on the basis of the longest dose interval and side effects.

You can look at the bevicizumab, to ranibizumab, to aflibercept, to brolucizumab, to faricimab drug programs. There are also dozens of failed programs in this area and perpetually new drugs and Gene Therapies looking to break into the market.

Perhaps an even more salient example would be pill based GLPs looking exploit the listed factors

Re: Clinical failure rates over the decades: yikes

#108

Post by s1artibartfast »

bonsai_spool wrote: post #105
s1artibartfast wrote: post #95

Earlier quoted context omitted.

Why isnt it rational? You spend the 1 billion for a ticket to win 30 billion/yr for the next several years. Is it rational to spend 1$ to make $100 10% of the time? A 99% failure rate would be break even.

> Why isnt it rational? You can spend that $1B to win a new category or that same money to maybe be non-inferior to Keytruda, but maybe fail. I think copycat design does happen, but I mostly notice it when drugs are being developed simultaneously at different firms. Perhaps it happens more beyond this, I'm unsure. Otherwise, it makes more sense to try to find an indication where you are approved and have no competiti…

I don't think you are looking at this from the rational economic perspective.

I'm not talking about biosimilars or strict copycats.

Completely novel indications are a tiny portion of Pharma development.

Lucrative and technologically viable untreated indications are few and far between.

Meanwhile, you have huge proven markets for treatments that impact millions of people with corresponding Revenue.

If you are skeptical, you can simply go look at the development Pipelines for the top 10 pharmaceutical Giants and see how many of their new programs are for indications with existing treatments versus orphan.

In recent years, approximately one-third of all novel new drugs approved annually by the FDA have carried a Breakthrough Therapy Designation. This corresponds to drugs that claim a substantial improvement over the standard of care for their target disease.

Re: Clinical failure rates over the decades: yikes

#109

Post by s1artibartfast »

peyton wrote: post #47
db48x wrote: post #46

Earlier quoted context omitted.

These are examples of ambitious drugs that wouldn’t have been attempted even a few decades earlier. But technology improved and the money was there so they tried anyway, and found success. But for any 3 successes there are still 27 failures because those 27 were equally ambitious.

Feels like a just-so story. How to quantify “ambitious”? If the goal were flight, would jumping off cliffs with wings like birds be “ambitious”? The most parsimonious explanation is either our models or methods (or both) are garbage. Something’s missing. The failure rate is insane, and writing it off as ambition or “biology is hard” rather than digging in does us no favors.

I don't know who you or the article are directing that criticism at.

Both models and methods are challenging. Biology is hard.

Who isn't digging in exactly?

Pharmaceuticals are more than a two trillion dollar market with Millions of scientists and engineers and doctors working diligently to refine the process.

There's tens of billions of dollars to gain for any company that comes up with even minor improvements to success rate.

Re: Clinical failure rates over the decades: yikes

#110

Post by analog31 »

asdff wrote: post #66
calf wrote: post #40

Earlier quoted context omitted.

I would have to reread the piece carefully but I don't think "lack of trying by Biopharma" is consistent with the author's main argument. Because he is still being somewhat critical of the way it is currently done (why he cites the other industries). I simply disagree with his final sentence since it requires a different set of essay arguments, and also is subjective in the way say a political centrist might say "the…

Most other industries barely innovate. Most industries are just buying off the shelf components and putting them together into larger widgets. Cars, computers, airplanes, that's the business. The components might get more efficient or performant but they generally do the thing they always did. If you squint it is basically the same car/plane/laptop as x years ago. They worked out the optimal car/plane/laptop shape a…

Indeed, I work in one of those businesses that seems to barely innovate. Many of our "new" products are mainly necessitated by obsolescence of components and changing applications. As I explain to people: The laws of physics don't change, at least as they affect our technology. For instance the earliest CCD and the latest CMOS image sensor share a lot of the same basic physics, and are made from the same chemical element.

In those industries, a person who deeply understands the theory behind the technology is assured of some job security. That's my job.

One area that has experienced more rapid innovation is software. And maybe it's not quite at the failure rate of drug development, but I think it's noticeably higher than for most "hardware" projects.

Post reply on HN