
A gene therapy to treat a rare, inherited form of blindness will cost $850K - joering2
https://www.washingtonpost.com/amphtml/news/wonk/wp/2018/01/03/gene-therapy-for-inherited-blindness-sets-precedent-an-850000-price-tag/
======
candiodari
> Only 1,000 to 2,000 people in the United States are thought to have
> deteriorating vision caused by this errant gene

This drug will only work on, let's say 1500 people. Of those, let's
optimistically say that 1/3 have insurance that will cover expensive
treatment. So 500 patients can be expected to be treated by this drug per
generation.

So this drug will optimistically get a revenue of $500 million per 2 decades
or so, or $25 million per year.

The number generally thrown around for getting a new drug researched and onto
the market is $200 million. So it will take 8 years just to break even
(although likely front-loaded once it becomes known that this drug exists),
and total revenue for this drug for the forseeable future is about 500
million.

Does this seem spectacularly unreasonable ?

~~~
superquest
No, it doesn't.

It would just really suck to be one of those 1000 that have gene and can't
afford the drug.

~~~
c3534l
They would be in the same position as they were before, only without that
system it wouldn't be worth researching the drug to begin with.

~~~
okasaki
Likewise if the company gave the therapy for free to everyone who couldn't
afford to pay $850k, they would be in the same position as they were before.

~~~
imcoconut
Before the reaearch endeavor, the company had x more dollars in cash. They
bore the cost with the expectation that it would generate cash flows in the
future (to hopefully more than offset the cost). The dollar cost was likely
quite large. So the company certainly would not be in the same position had
they not decided to develop the drug. There was no cost the affected
genetically blind, however. They only now have the option of potentially being
able to get a new treatment.

------
codeulike
So Luxturna is a DNA sequence embedded in the AAV2 virus
([https://en.wikipedia.org/wiki/Voretigene_neparvovec](https://en.wikipedia.org/wiki/Voretigene_neparvovec)).
It seems like they modified the Kozac (header, basically) of the DNA slightly
(see Wikipedia). But essentially what they're doing is injecting the 'correct'
DNA sequence into people with a biallelic (both copies) mutation on the RPE65
gene. The AAV2 virus is there as a delivery mechanism to get the DNA into the
cells more efficiently. The injected DNA then hangs around (loose, I think) in
the cell and will get read and the correct proteins get manufactured even
though the patients main copies of the gene are faulty.

The virus bit might be hard to do, and maybe editing the header of it. I'm not
sure. I guess that probably is quite hard.

But manufacturing DNA and injecting it is fairly trivial, as in this guy with
a PhD and a small lab was able to do it for about $400. There are biotech
companies who will just make the DNA for you.
[https://www.theguardian.com/science/2017/dec/24/josiah-
zayne...](https://www.theguardian.com/science/2017/dec/24/josiah-zayner-diy-
gene-editing-therapy-crispr-interview) ... this was using CRISPR which is like
a DNA find/replace, so in some ways more sophisticated than the way Luxturna
works.

I'm not saying anything about the price of this treatment per se, obviously a
load of R+D and regulatory ballet had to be done here, but just saying the
basic building blocks of some gene therapies are quite a bit cheaper than I
imagined.

~~~
zimpenfish
Although the opinion of real biologists seems to be that Zayner is a snake oil
peddling hack who doesn't know what he's doing.

e.g.
[https://freethoughtblogs.com/pharyngula/2017/10/14/i-could-u...](https://freethoughtblogs.com/pharyngula/2017/10/14/i-could-
use-bigger-muscles-but-im-not-going-to-get-them-with-biotech-in-my-garage/)

~~~
codeulike
That guy misunderstands the point of Zayners stunt, and also misunderstands
the kits that Zayner sells (they are kits for using crispr on yeast in a Petri
dish). Zayner acknowledges that his arm injection stunt is likely very
inefficient.

Still I'm not going to defend Zayner, he probably is a bit of a dick.

But the point is that you can modify the DNA of at least a small number of
your own cells in a rough untargeted way for about $400. That's quite
surprising. Makes you wonder what might be going on behind closed doors
elsewhere.

edit: Here's Zayner's write up of his stunt:
[http://www.ifyoudontknownowyaknow.com/2017/10/the-first-
huma...](http://www.ifyoudontknownowyaknow.com/2017/10/the-first-human-to-
attempt-crispr-gene.html) (possibly dodgy ads, adblock recommended)

------
sedtrader
This is why the majority of medical breakthroughs and innovations occur in the
US. Sure capitalism has its negatives, but its positive is that it provides
vast financial incentives for people to create new solutions while at the same
time filling a need for humanity. $850k is a hefty pricetag, but the ability
to see your loved ones is priceless. Win/win for everyone involved

------
comstock
The story is about the pricing, but the drug itself was more interesting to
me:

[https://en.m.wikipedia.org/wiki/Voretigene_neparvovec](https://en.m.wikipedia.org/wiki/Voretigene_neparvovec)

It’s a gene therapy delivered in a viral vector. They inject it (into your eye
which much be fun). It appears to be one of the first approved gene therapies.

~~~
stuaxo
Could something similar be injected into you're eye and turn it into a
different kind of eye ?

~~~
codeisawesome
This might be limited by what the sum total real capability is of the entire
vision system. An eye that can receive extra wavelengths is useless without
the Neurons that can perceive and project into our conscious mind. To imagine
injecting viruses that will change the genetics of the brain is a major leap
of discomfort.

~~~
fab1an
>An eye that can receive extra wavelengths is useless without the Neurons that
can perceive and project into our conscious mind.

Not necessarily. For example, consider that neurons in our auditory cortex
aren't different from neurons in our visual cortex!

What is different about them (and the "subsequent" perceptual/conscious level)
is that they receive different inputs, and have learned the systematicity of
how these inputs behave in relation to the body's own actions.

This is related to the "Sensorimotor Contigency" theory of consciousness [1],
which would predict that it should in fact be possible to process entirely
different types of sensory input, given long enough exposure and a clear
systematicity of the input signal.

[1]
[http://www.scholarpedia.org/article/Sensorimotor_theory_of_c...](http://www.scholarpedia.org/article/Sensorimotor_theory_of_consciousness)

~~~
GFischer
Some experiments by "cyborgs" are relevant... I remember that one of them
added to himself _" a sensor that detected Earth's magnetic field."_

[https://www.wired.com/2007/04/esp/](https://www.wired.com/2007/04/esp/)

and it seems the experiment has been updated:

[https://www.theguardian.com/technology/2017/jan/06/first-
hum...](https://www.theguardian.com/technology/2017/jan/06/first-humans-sense-
where-north-is-cyborg-gadget)

 _“As we walk down the street there’s radiation, X-rays, infrared and
ultraviolet, as well as the electromagnetic field of the planet. So we want to
create new senses to become aware of our environment.”_

and

 _Harbisson, who is colourblind, has an ‘eyeborg’ that allows him to “hear”
the light spectrum (including infrared and ultraviolet), while Ribas has a
sensor in her elbow that vibrates when an earthquake occurs anywhere in the
world._

------
aladoc99
Cost-effectiveness guidelines somewhat arbitrarily state that an expense of
$50,000 per year of life is reasonable, since this is the estimated average
annual cost of dialysis therapy. This gene therapy is sight-saving, but not
lifesaving, so cost-effectiveness analysis must consider QALYs -- quality-
adjusted life-years. How much is a year of blind life worth relative to a
sighted year? There can be no definitive answer to this, but one guesstimate I
found was 80%. Using this and the $850,000 total cost, one finds that the
treatment would have to provide on average 85 sighted years to be considered
cost-effective. Insurance companies could use this kind of analysis to
restrict the treatment to infants.

------
jstanley
If someone gets treated with this therapy, and then has children, will the
children inherit the parent's original gene or the repaired gene?

~~~
refurb
No. The genetic alteration is limited to the person who receives the therapy.
Reproductive cells aren't affected.

~~~
jstanley
So if you have this, at a cost of $850k, is it then unethical to have
children, knowing that there's a high chance that they'll subsequently have to
pay $850k in order to be able to see?

I suppose, more generally, even in the absence of an $850k fix, if you have
genetic blindness, is it unethical to have children?

~~~
JoeAltmaier
Not in our current human society, where new cures are invented every week. Its
no longer a life sentence for your children; its a temporary setback.

~~~
TeMPOraL
This is what I came to believe too, and it's yet another reason why I believe
the highest priority for the society is to _stabilize what we have now_ \- as
opposed to constantly try to tear everything down in order to win something
for one's group.

Looking at the last decades, it's no longer unreasonable to think we might
cure things like blindness or deafness, or paralysis, in the next 100 years.
But that can only happen if our technological civilization survives
uninterrupted. If it spirals out of control and self-destructs, we'll be stuck
in a pre-industrial age for thousands (if not hundreds of thousands) of years,
until the Earth replenishes some of the easily accessible high-density energy
sources we pretty much entirely mined out.

------
phnofive
Is there data on how effective this is, and how the vision of those treated
compares?

I can’t imagine the price I’d put on a sense; nice to know you can literally
get half of the price for a single eye treated.

~~~
aaavl2821
Check this out: [http://ir.sparktx.com/static-
files/3f12ea2d-7f52-4ccd-93d4-c...](http://ir.sparktx.com/static-
files/3f12ea2d-7f52-4ccd-93d4-c8ee7df871d2)

It is their corporate presentation; lots of data on the drug starting around
slide 10. these are data from the clinical studies required for FDA approval.
Investor presentations (for public companies) tend to have good summaries of
the key data on a drug; for more info, you can read scientific publications on
the drug in academic journals

------
wozmirek
Just wondering, why there's no mention of this being free, i.e. 100%
government funded. Something like this essentially transforms somebody's life,
allowing him/her to work, not being reliant on others etc. Not to mention the
(oh, sadly) not quantifiable humanitarian reasons.

~~~
stingraycharles
Because it's a slippery slope. You can always argue that a blind person is
able to work in some way (callcenter, software dev, etc), and/or you can argue
the same for other diseases. Where do you draw the line ?

That argument aside, I am of the opinion that all healthcare should
(eventually) be free so that arguments like these become moot.

~~~
whiddershins
I used to think all healthcare should be free. One observation changed my
belief:

“The demand for healthcare is effectively infinite.”

There really is no limit to a person’s healthcare needs. It’s a moving target.
The only way to make all healthcare free would be to start by defining exactly
what is and isn’t healthcare. That’s exactly what is upsetting about the
concept of government provided services. At some point someone will have to
say “enough.”

Who would decide that, and how?

~~~
wozmirek
Sure thing, I think the current soft limit is set by your doctor, who will
e.g. postpone your non-essential (e.g. cosmetic) treatment. Blindness is just
that - blindness. I see no slippery slope here.

Currently experienced three health systems: Polish, US and German; first is
woefully underfunded and public, second is ultra-private, third is a properly
funded public system.

In Poland, I used both public and private, using private whenever I could
(think dentist, blood test etc.); in US I never went to the doctor because I
had to pay extra; in Germany I feel comfortable and happy with the fact that I
get public healthcare for my taxes. Actually planning a string of visits to
the dentist ;)

------
refurb
$850K may seem like an outrageous price, but Steve Miller, CMO of Express
Scripts, who has been a vocal critic of drugs prices over the years, called
this price "reasonable".

------
tudorw
"Clinical data shows that the drug works at[sic] up to four years in some
patients"

"a partial refund if the drug does not work in the first three months"

So is it $850,000 every four years ?

~~~
refurb
We don't know. I assume the 4 years came from the clinical trial (I.e.
Patients were followed for 4 years).

------
mannykannot
We are going to see more of this sort of thing. The elephant in the health-
care costs debate is, ironically, that we are becoming much more capable at
it.

------
bufferoverflow
I predict someone will figure out how to edit the genes the same way with off-
the-shelf kits within a year or two and will publish it for free.

~~~
comstock
Personally I somehow doubt this (in this case).

The disease effects a small number of people (1 in 4000), and doesn’t cause
complete blindness in all those effected.

It’s delivered in a viral vector, kind of not so easy to do yourselves I’d
guess. Probably the easiest way would be to get hold of some and culture the
virus yourself? Then just make as much as you want.

Still injecting something made without strict QC into your eye might not be so
appealing.

~~~
bufferoverflow
[https://www.fastcompany.com/40477808/genetic-modification-
is...](https://www.fastcompany.com/40477808/genetic-modification-is-just-an-
injection-away-if-youre-feeling-lucky)

~~~
comstock
The article is well written and interesting.

The kit looks fun, but I don’t think it as (easily) be used to replicate this
work, it’s just too different.

The issues mentioned in the article also apply.

------
YeGoblynQueenne
Science and technology make the world a better place - for those who can
afford it. The rest can go get stuffed.

I remember an old psychological test where you were presented with a scenario
where a member of your family is sick and while there exists a drug that can
cure them, you cannot afford it. You're given the option to break into the
local pharmacy and steal the drug- and asked whether you would do it. The way
you answer the question is an indication of your moral development stage. If I
remember correctly, the idea is that the most morally developed individuals
will decide that stealing the drug is not moral, that if everyone stole what
they needed without regard to the interests of the original proprietor, there
would be anarchy and society would collapse. So on the whole, the moral
decision is to not steal the drug, even when your relative needs it.

Well, if society allows a life-saving drug (or, indeed, a blindness-curing
treatment) to be unaffordable to those who need it, then that's already a
society that is not serving its members' interests. What the hell do I care if
society can support science advanced enough that it can cure blindness, if it
won't cure _my_ blindness? I'm expected to do the moral thing and sit nicely
and not rock the boat- but others are not expected to help me, in my need?
Bugger that for a game of soldiers!

A society that leaves people blind when it can cure them is just as useless as
one that burns. So let it burn.

I'd steal that drug in a heartbeat.

Oh btw- in another article about this miracle cure, I read the ridiculous
claim that blindness will cost a person about $1million in their lifetime, so
the $850k price tag is justified. I don't see this claim in this article, but
it just goes to show what some may consider "fairness": "blindness robbed you
of $1million, now we're gonna take another".

~~~
dominotw
That's what they said about indoor plumbing, air conditioning ect. Yea new
technology is expensive to start. Should people not work on anything that
cannot be made available cheaply from the get go.

~~~
JoeAltmaier
As mentioned above, such therapies cost a few dollars to create and deliver.
The price is artificial.

~~~
TeMPOraL
Marginal costs may be small, but the initial costs are large. Once the initial
costs get repaid, and as third parties reverse-engineer the process, the price
of the treatment will drop.

~~~
JoeAltmaier
In a free-market R&D ecosystem, sure. The issue is, do we want that to be how
it works. And its debatable how much of the initial cost should be loaded onto
this cure, as the work builds on other work, and the technique will produce
more interesting results in future.

And in this case, does it boil do to publishing the dna fragment? Is this
another 'patenting a number' discussion?

~~~
TeMPOraL
I don't feel we want that to be how it works, but I also have no good ideas of
how it could work differently, while retaining the speed of discoveries.

