
Quietly another drug candidate disappears - dcminter
https://blogs.sciencemag.org/pipeline/archives/2019/09/17/quietly-another-drug-candidate-disappears
======
pmiller2
Isn’t this the normal, expected, and preferred method for a drug to fail? The
alternative failure mode is: drug gets to market, later on is found to have
horrible side effects and harms a lot of people. See _e.g._ Vioxx.

~~~
dcminter
Oh, absolutely - but I think Derek's point in the article is that many critics
of "Big Bad Pharma" who see the profitable drugs making it to market are
unaware of the expensive failures that never make it that far.

~~~
skohan
> many critics of "Big Bad Pharma" who see the profitable drugs making it to
> market are unaware of the expensive failures that never make it that far.

But I think this image - that pharmaceutical companies are constantly risking
their financial future pouring resources into research for new drugs which
will finally cure some disease that has plagued humanity - is also a
mischaracterization of reality.

For instance, drug companies also spend a large portion of their research
budget developing "novel compounds" which are based on small chemical changes
to existing drugs, just for the purpose of extending their patent and
increasing the profitability (read: cost to consumer) of an existing
treatment. So it's not as if all the resources they put in to research
represent some altruistic good.

To be honest, I think the incentive structure for drug companies, like many
things in healthcare, is just not ideal for producing the best outcomes. Their
ideal business model is to own expensive drugs which sick people have to take
for their entire lives. If they produce truly curative treatments, that's
actually a net loss for them.

As some people have suggested, it would make a lot of sense to nationalize
drug research in the US. The idea is you bring the top pharmaceutical
researchers into the NIH, and while this would require a big up-front
investment, you might even be able to operate at a profit by licensing the
drugs they develop to the rest of the world.

Also, in a single-payer world, you would have the healthcare provider under
the same financial umbrella as the people creating the drugs. As a result, the
incentive would be to drive treatment costs down.

~~~
new299
> just for the purpose of extending their patent

I don’t understand this point, though I’ve heard it before. If the original
patents expire, the original drugs can be manufactured as generics right? If
the new patents provide no new benefit, don’t use them?

> The idea is you bring the top pharmaceutical researchers into the NIH...

Projects I’ve seen suggests that technology development carried out in an
academic context often requires significant refinement (or complete reworking
tbh) when being brought to market. So, it’s not clear to me how well the model
you suggest would work.

Perhaps it would be best to have a public organization that manufactures
genetic drugs first and build from that. But... I think that may also have
issues.

~~~
DanBC
> I don’t understand this point, though I’ve heard it before. If the original
> patents expire, the original drugs can be manufactured as generics right? If
> the new patents provide no new benefit, don’t use them?

Have a look at Avastin (Bevacizumab) and Lucentis (ranibizumab).

[https://www.nih.gov/news-events/news-releases/avastin-
lucent...](https://www.nih.gov/news-events/news-releases/avastin-lucentis-are-
equivalent-treating-age-related-macular-degeneration)

AMD is a leading cause of blindness.

Avastin is a cancer medication that was found to be effective to treat Age-
related macular degeneration (AMD), although it wasn't licenced for that
usage.

The makers reformulated and came out with Lucentis which they licenced for use
with AMD.

Lucentis is considerably more expensive than avastin.

[https://www.bbc.co.uk/news/health-30138097](https://www.bbc.co.uk/news/health-30138097)

> Lucentis typically costs about £700 for an injection, but the price for
> Avastin is about £70.

In the UK the drug companies not only forbade off-label use of avastin, but
they went to court to prevent this use. They lost.

[https://www.hsj.co.uk/finance-and-efficiency/breaking-nhs-
wi...](https://www.hsj.co.uk/finance-and-efficiency/breaking-nhs-wins-
landmark-legal-battle-against-drug-
companies/7023422.article#.W6TH58DoL6U.twitter)

~~~
Consultant32452
It sounds to me like the cost to get a drug certified for use is the problem
here. In the US it's literally a billion dollars. If it were cheaper, it would
be worth paying for certification of a new use for an existing out of patent
drug by a generic manufacturer.

~~~
mandevil
So called "Off-Label" usage is totally legal in the US right now, for free.
Drug companies get in trouble for _advertising_ off-label use (that is totally
verboten, the FDA regulates drug company advertising and so it can only be
done for something the FDA has approved), but your doctor can prescribe
something for off-label use totally legally at any time. Estimates are that
about 20% of all prescriptions are for off-label use.

Also, the billion dollar number is for developing a new medicine, and includes
the costs of all the attempts that failed along the way, not for running tests
to get an already approved drug certified for a new usage.

------
russellbeattie
Slightly off topic, but the author of this article is Derek Lowe who I know
from his series called "Things I Won't Work With" which contains some amazing
facts and hysterical observations. He wrote a new entry in August that I
hadn't seen (the first in a few years). Definitely check it out.

[https://blogs.sciencemag.org/pipeline/archives/category/thin...](https://blogs.sciencemag.org/pipeline/archives/category/things-
i-wont-work-with)

~~~
dcminter
By the by it's often worth skimming through the comment threads on those
articles for entertaining posts by chemists reminiscing about their own near-
misses!

------
ncmncm
For conditions that are as poorly defined as fibrosis -- i.e., a symptom is
noted, but not a cause -- RCTs can produce tragically misleading results,
resulting in excellent therapies being dropped.

Apparently most treatments for depression fall in this range, which may be why
new treatments arrive so rarely. Depression is a "wastebasket" diagnosis, with
many, many causes. Any given treatment only helps with one or a few. Which
variety you have can only be discovered by seeing which medications fix it, so
putting together a set of candidates who have what one treatment would fix is
impossible without actually trying it on them first.

If fibroses have this character, the only medication we can hope will get past
the gauntlet will be palliative treatments, that reduce the body's common
response to all the causes, without addressing any of the causes.

It's as if we were treating "ague", and not differentiating flu from malaria
or bacterial pneumonia. Since a candidate antibiotic may only help the few
with gram-negative bacterial infection, it looks not sufficiently effective,
and is dropped. We are left with aspirin for fever and decongestants, while
the infection rages unchecked.

------
dna_polymerase
> Drugs fail all the time, most of the time rather quietly, and all the work
> and money that went into them just sort of vanishes.

This seems problematic to me. Wouldn't it be generally preferable to publish
everything about their work so others can learn from it? Obviously big pharma
would be against that, but in the general pursuit of advancing medicine it
would help, so federal regulation?

~~~
jcranmer
Derek is speaking here about how the effort is vanishing in the public eye.
But if you're someone doing research on a drug target, these sorts of failures
are going to be visible to you when you do searches for previous attempts or
approaches at the problem, at least if they advance as far as initial clinical
trials.

------
ImaCake
I know some people who work with mice models of fibrosis (but in a COPD
disease context). They work extremely hard and produce mammoth amounts of
experimental data. They could always do with more funding and more manpower,
but I feel good that at least some of the people working on these diseases are
exactly who you would hope would be.

------
Angostura
I don't know enough about the area to be able to interpret this seemingly
rather important sentence:

> word has just come out that the study has been terminated with only about a
> third of its patients enrolled.

Was the study terminated because they couldn't find sufficient guinea-pigs? Or
was the study terminated for other reasons before recuitment was complete?

~~~
SiempreViernes
Well, the title of the linked article is "Biogen axes phase 2 study of lung-
scarring med due to 'safety concerns'"

