HN Gopher Feed (2017-07-13) - page 1 of 10 ___________________________________________________________________
'Living Drug' That Fights Cancer by Harnessing Immune System Clears
Key Hurdle
307 points by daegloe
http://www.npr.org/sections/health-shots/2017/07/12/536812206/li...___________________________________________________________________
aaronbrethorst - 3 hours ago
"While Novartis will not estimate the price it will ultimately put
on the treatment, some industry analysts project it will cost
$500,000 per infusion."Meanwhile, the latest version of the US
Senate's healthcare bill includes the so-called Cruz Amendment[1],
which would allow insurance companies to offer health insurance
plans without essential health benefits, which would allow lifetime
caps on insurance[2], which could mean that your six year old with
recurring leukemia gets pulled off their treatment when they're
halfway through. Not because you did anything wrong, per se, but
because maybe your employer refuses to spring for health care plans
with more than an $x dollar cap. Or you never anticipated something
so horrific and catastrophic happening to your family.[1]
https://www.nytimes.com/2017/07/13/us/politics/senate-republ...[2]
https://www.brookings.edu/2017/05/02/allowing-states-to-defi...
logfromblammo - 2 hours ago
You could always pay the alternate price of kidnapping a Novartis
executive's child until the treatment is completed, and then
surrendering yourself to a lengthy prison term afterward. I
can't pay $500k out of my own pocket, but I can buy a roll of
duct tape and rationalize the hell out of an ethically tricky
situation.That's one of the classic posers to gauge someone's
level of ethical maturity, isn't it? Your child is dying, and
you cannot afford the treatment. Would you steal it instead of
buying it? Why?
sloppycee - 2 hours ago
That sounds horrible.Although, I do wonder what effects there
would be if a cancer cure-all were discovered.Since nearly
everyone would need the treatment at some point, it wouldn't
really be insurance anymore; more like a mortgage.
Young_God - 3 hours ago
A friend of mine is alive today because he was part of one of the
early trials. He had been told by his doctor, just before he was
accepted into the trial, that he should start putting his affairs
in order.
stillfinite - 7 hours ago
The significant thing about CAR-T cell therapy is that it's not
very specific to the type of cancer - all cancer cells have damaged
DNA that leads to the productions of antigens. Leukemia is the low-
hanging fruit because it's easy to inject the T-cells back into the
body right where the cancers cells are. It's hard to tell whether
you could get enough T-cells to diffuse out of the bloodstream to
have an effect on something like prostate cancer. It would be a
real breakthrough if you could overcome that hurdle, because then
you would have a treatment that works on many different cancers
without much modification.
hwillis - 6 hours ago
Real, actual question: would it not work to just inject t-cells
deep into my taint in that case?
Cerium - 5 hours ago
What I got out of the article was that the approach here seems
to be that you create a small number of improved t-cells and
inject them. Then these improved t-cells will respond correctly
upon contact with cancer cells. At that point they will
multiply to meet the required demand. The initial injection
would be more like a vaccine than a drug.
vibrio - 5 hours ago
"local' anticancer treatment is achievable but not really
effective. the promise in the CAR-T is persistence of the cells
and systemic distribution so they can surveil for micro
metastases and minimal residual disease, hopefully eliminating
it. I'm not sure injecting a ton of cell into ones taint would
give the cells the best opportunity to persist and provide
systemic prevention.
HillaryBriss - 6 hours ago
i second that question. if they can carry out needle biopsies
of the prostate and other cancer locations, if they can
surgically remove cancerous tissue -- why can't they also get
these modified cells to the cancerous locations somehow?
jfarlow - 5 hours ago
The other 'cool' part about CARs is that 'without much
modification' is not near so large a challenge as it is for small
molecules. Certainly there are regulatory barriers, but
scientifically, the ease with which you could just (genetically)
pop on a custom nanobody/binding domain is many many orders of
magnitude less than trying to find a small molecule to hit a
different target.In a decade or two, I wouldn't be surprised if
CARs were being deployed that were entirely customized to a
patient's cancer, where the scaffolding was 'FDA approved', while
the binding domain was cultured to specifically react to this
patient's cancer, encoded into DNA, printed and designed within
the space of a few hours or days. The kind of customizability
that comes from a genetic therapy opens a lot of new doors.
tcbawo - 1 hours ago
Perhaps we'll even be able to generate individualized tissue
samples in order to test out side effects prior to treatment
suddenseizure - 5 hours ago
The downside with adaptive immune system therapy (like CAR-T
therapy) is that it doesn't work as well with cancers with fewer
mutations that the T cell can detect as anomalous.My wife has
brain cancer and has been reading about all the immunotherapies
available. Unfortunately brain cancer tends to have much fewer
mutations than say, lung cancer. However there are innate immune
system therapies being researched that might be more promising in
those cases.
sjg007 - 2 hours ago
So sorry to hear this. It sounds like you guys are doing the
right research. Being in a similar boat, I think that the
checkpoint inhibitors look very promising. I try to keep up
with the field as best I can. The hard part is you have to
find an appropriate clinical trial for whatever you and your
doctor think is best... Also, just as an FYI, the NCI is
starting up a new precision medicine trial (NCI-MATCH) to
target specific pathways instead of tumors... but I'm more of
the opinion you have to do combination chemotherapy and
modalities unless the drug is super effective. But then again
I'm not an oncologist or a doctor.
scottLobster - 6 hours ago
I wonder though if just having these types of cells in the
bloodstream could limit or even prevent cancers from
metastasizing. That would provide a massive increase in
survivability in and of itself.
sjbase - 8 hours ago
Does anyone know: what are the failure rates like for the gene
editing technology being used for this? Thinking like a software
engineer, are there transposition errors (GATC --> GTAC) ,
atomicity issues (GATC --> GA)? Mutations afterward?
jfarlow - 7 hours ago
Congratulations! The Chimeric Antigen Receptor (CAR) deployed here
is very much unlike the standard 'small molecule' drug that
'disrupts a bad thing', and much more like a rationally engineered
tool using the body's very own technologies to overcome a
particular limitation. In this case, it gives the patient's own
immune system a notion of what the cancer looks like.If you want to
build your own 'living drugs' we've built a digital infrastructure
to allow you. Though we just made public our generic protein
design software (thanks ShowHN! [1]), we're employing the same
underlying digital infrastructure to build, evaluate, and manage
CAR designs in high throughput [2]. The drug approved here was
painstakingly designed by hand, while we think the technology now
exists to permit many more such advances to be created at a much
more rapid pace.[1]
https://news.ycombinator.com/item?id=14446679[2]
https://serotiny.bio/notes/applications/carDesign your own 'living'
protein drugs here right now: https://serotiny.bio/pinecone/ (and
let us know what you think, and how we can make it better!)
[deleted]
skummetmaelk - 6 hours ago
3...2..1.. Prion disease!Seriously though, how would you prevent
such automated designing from having unintended side effects?
e40 - 14 minutes ago
3...2..1.. Prion disease!Can you explain that?
jfarlow - 6 hours ago
The software is useful because it allows you to have some idea
of the function of each component prior to their assembly.
Further, at this point, the software is designed for R&D far
far upstream of being put directly used as a therapeutic.
Finally, if a design causes some problem, we want to know that
- we allow that undesirable property to be discovered in the
laboratory, annotated, and communicated so that others know to
not use such designs.
skummetmaelk - 6 hours ago
Is it actually possible to construct proteins from functional
components like we design digital logic and software? Don't
the parts interact in highly complex ways that take a lot of
compute time to solve?
jfarlow - 6 hours ago
If you're trying to compute from first principles (atom by
atom), yes, exactly - that's a very hard problem. And if
you're rearranging entire protein domains rather than point
mutations - that's an intractable problem. And it is
precisely the problem we are trying to solve - how can you
have any idea what the function of a novel protein will be
when you are swapping around hundreds of amino acids at a
time?We've taken a different approach. A 'small data'
approach, where we manually, and semi-automatedly ingest
hard-earned empirical data about each domain, and make it
computationally accessible. We give heuristics and logic to
a biologist's intuition about 'this protein never seems to
work when it's at the N-terminus', rather than trying to
compute why it doesn't work by simulating the movements of
100,000 atoms over 10ns. And though many (generally
synergistic) interactions won't be predictable in this
manner, many will be. We help get you to those designs
likely to work as quickly as possible. And the more
empirical data ingested, the faster we think we can get you
there. Further, even if it's not 100% effective at
predicting the single best design, enriching the search
space of a large (and expensive) screen is itself
valuable.Life already mixes & matches DNA to create new
functional all the time, we're just making that same
process explicit and accessible. It turns out the function
of any given protein domain is actually reasonably robust
to being split up and rearranged. Especially when the goal
is 'some function', or 'good enough', and you're not
messing with or trying to tune a protein absolutely
required for life.
ceejayoz - 9 hours ago
> Another big concern is the cost. While Novartis will not estimate
the price it will ultimately put on the treatment, some industry
analysts project it will cost $500,000 per infusion.Welp, guess my
insurance premiums aren't stabilizing anytime soon.
seibelj - 9 hours ago
There won't be that many people who need this drug, and
supposedly it's a one-time cure that isn't a life-long drug
treatment. I'm a layman when it comes to biotech, but my hope is
that longterm the prices come down for this and other drugs that
use a similar technique to treat diseases. I'm happy researchers
are focusing on cures rather than "living-with" a disease.Also,
shoutout to Boston (and Cambridge) which I don't think gets
enough love on HN. #1 in the entire world for biotech, #2 for
software, #1 for higher ed, #1 for healthcare, you can actually
afford to live here, solid public transportation, amazing skiing
/ hiking / beaches, NYC in 4 hours. If you are tired of SF think
about Boston
im_down_w_otp - 9 hours ago
You lost me at "amazing skiing" ;-)
rhexs - 9 hours ago
You can afford to live there? I was looking at 1 br apartments
in Cambridge and it was pretty darn close to SF Bay.
Interviewers I was talking to said they commuted in 45 minutes
just so they could own a house.
nck4222 - 8 hours ago
>commuted in 45 minutesI live in and work in Boston, and my
commute is 45 minutes. I'm planning to move further out to
buy a house, and my commute will probably still be roughly 45
minutes.Unless you live within walking distance of your
office or feel like you have a safe enough bike route to the
office, 45 minutes is a fairly standard commute here.
tomkinstinch - 9 hours ago
The unspoken assumption is that it's affordable if you have
roommates (or a solid dual-income household). I have a place
in Providence, RI and commute to Cambridge, MA by train (38
minutes to South Station via Amtrak, double that via MBTA).
It's a shorter commute than when I rented in Brookline.
Because of all of the Boston-area colleges, students set the
standard. The housing stock is higher quality (and lower
price) once you escape Boston/Cambridge, where students will
live in any sort of derelict apartment, and use loans to pay
inflated prices for the privilege. Boston has many things
going for it, but the housing market is a real problem. Don't
get me started on "broker fees"...
nerdponx - 7 hours ago
it's affordable if you have roommatesThis is the story in
NY too. It definitely does not qualify as "affordable" for
anyone with a family.
agentgt - 6 hours ago
I live in Waltham and while I don't work in Boston (work from
home) it only takes me 15-25 minutes (depending on where in
the city) to get into Boston.The Boston area has awesome
suburbs that aren't really suburbs like Newton, Arlington,
Waltham, Brighton, Melrose (where incidentally Martin Fowler
lives) etc. I know everyone wants to live in the city cause
its cool but these mini cities are pretty darn cool as
well.From most of these areas you can get into the city in 20
minutes by car. 40 minutes if there is bad traffic.And of
course there is public transportation.Compare this to most of
the metropolises in America: Atlanta, Dallas, Houston, etc
that have massive traffic and suburbs that are truly suburbs
(boring as can be).
jseliger - 5 hours ago
Compare this to most of the metropolises in America:
Atlanta, Dallas, Houston, etc that have massive traffic and
suburbs that are truly suburbs (boring as can be).Yet those
boring metropolises have something key: affordable housing.
Which is why the world is looking a lot more like them:
http://www.newyorker.com/magazine/2017/07/10/americas-
future.... While most MA suburbs prohibit most development,
thus causing prices to skyrocket: https://www.bostonglobe.c
om/business/2017/05/16/somerville-h...
agentgt - 1 hours ago
I generally agree but often those affordable houses are
massive cheaply made McMansions (particularly in
Texas).Living in New England I'm often envious and this
is probably coming from jealously but really family's of
5 don't need 6000 square feet, a pool, a 3 car garage,
and 2 acres of land. You can always live like the
Europeans and most of the rest of the world does and
there are condos sub 300,000 in the MA suburbs.
numbsafari - 9 hours ago
Funny... Weren't these studies done in Philly, not Boston? And
isn't the Novartis lab based out of Switzerland? I missed the
part about Boston in this article...
gozur88 - 6 hours ago
This won't affect your insurance - the patient population is too
small.Now, if a similar treatment gets approved for, say,
prostate cancer... that's going to affect your insurance.
philjohn - 4 hours ago
Eh, probably not for prostate cancer, very treatable if caught
early, and a lot of people have "watchful waiting" as it does
less harm to leave it in for a while than take it out.Now, if
there was a gene therapy for breast, colon or liver cancer,
then it would be a problem.
gozur88 - 4 hours ago
Yes, well, that's all true for prostate cancer, but if we had
a drug that could cure it people would want that over surgery
or "watchful waiting".
philjohn - 3 hours ago
It depends ... the treatment may be wanted, but unless it
has a much higher cure rate than the current regimen, no
insurer will offer it, and no single payer system will
either.In the UK we have NICE (National Institute for
Clinical Excellence) who make the decision over what drugs
can be used on the NHS (and most private insurers use the
same gradings), if it doesn't offer a clear benefit over
the existing treatment in both effectiveness and then cost
it won't be approved.
zamalek - 5 hours ago
> the patient population is too small.I think that cancer is
one of the great filters. At some point a species will develop
an unreliable way to treat cancer (chemotherapy); at which
point cancer becomes a genetic problem as natural selection is
displaced by medicine. Over many generations, this will kill a
species unless a reliable cure is found - we seem to have that
cure. Our cure is symptomatic (cancer being the symptom) but
the same technology could eventually be used for designer
genetics.Essentially, more and more people are going to rely on
this treatment until we are able to completely eradicate
hereditary cancer. Probably not in our lifetimes.
bykovich2 - 26 minutes ago
What is the selective pressure /for/ cancer-predisposing
genes? And it's not as if most cancers act as a reproductive
filter -- the majority of them emerge well after the onset of
reproductive ability, drastically reducing, if not
eliminating, their selective effect.
zamalek - 1 minutes ago
> What is the selective pressure /for/ cancer-predisposing
genes?Evolution does not and never has selected /for/
things. It is a process of elimination. What this means is
that, since the advent of chemotherapy, we have eliminated
selection /against/ certain types of cancer.> the majority
of them emerge well after the onset of reproductive
abilityCorrect, we have never had an impact on that and
likely won't for a very long time (we don't know enough
about our genome to do so). As-per this study, we have been
curing cancer in children (as we absolutely should) with
very little knowledge as to how/why they developed cancer
so young. Will their children also be at risk for leukemia?
What about their millions of descendants? We don't know. If
treatments like this work out then we might not have to
care.
gozur88 - 5 hours ago
But cancer isn't primarily a genetic problem; it's a
consequence of the way our bodies work at the cellular level.
We all accumulate genetic damage over time from a variety of
sources, and we'll all get cancer eventually if something
else doesn't kill us first.
zamalek - 4 hours ago
That is the story for most people today but is not the
entire story. If your mother had breast cancer then you are
at a higher risk - if not for genetics that would be magic.
That is why I specifically said "hereditary cancer."
philjohn - 4 hours ago
Yep, other hereditary cancer syndromes too, such as Von-
Hippel Lindau, which is a mutation in a tumour suppressor
gene.
pinaceae - 9 hours ago
how much is getting cured of cancer at a very young age worth?
dying vs. living another 80-90 years?less than a Tesla? more than
a house?interesting questions arise around immuno-oncology.should
Apple be the most profitable company - or someone that literally
cures cancer?
orbitur - 9 hours ago
> how much is getting cured of cancer at a very young age
worth? dying vs. living another 80-90 years? > less than a
Tesla? more than a house?It's worth so much that a person
shouldn't be required to pay for it. Like a right.
deelowe - 8 hours ago
Whether or not an individual pays for it has nothing to do
with the pricing the manufacturer sets. In fact, setting
prices becomes even more of a concern when these things are
being funded by tax dollars as the government is going to
need a way of determining what's reasonable.
phkahler - 7 hours ago
I still think it might be best if government funds the
research and then allows anyone with the capability to use
it. In other words, no patents. There would be competition
and the price would come down. The big problem I have with
this suggestion is that I don't believe in governments
ability to do anything cost effectively - even funding
research - but I might be wrong.
HillaryBriss - 6 hours ago
Dean Baker, an economist, has written here and there
about alternative ways to pay for drug research:"There
are clearly better and worse ways to structure a system
of government financed research. For example, the Free
Market Drug Act, a bill recently introduced in the U.S.
Congress, called for establishing a set of competing
government corporations that would be evaluated at
periodic intervals (e.g. 10 years) for the quality of
their work. The worst performers would be put out of
business with new ones created to take their place."More
here:http://www.paecon.net/PAEReview/issue32/Baker32.htmh
ttp://cepr.net/publications/briefings/testimony/drugs-
are-c...
refurb - 5 hours ago
Considering the number of poorly performing gov't
programs, I'm sure the "quality of their work" would be
based on things other that actual output. Nepotism and
buying votes are probably more likely.
toomuchtodo - 8 hours ago
When a manufacturer sets the price, they want to recoup the
costs and then make a profit on each unit sold.When a
government funds the research, the marginal cost for each
unit provided is time and materials, with no
profit.Government funds projects every day that are waste,
spending tens, even hundreds of millions of dollars. We can
continue to pour money down the F-35 drain but not provide
healthcare? Make America Intellectually Honest Again
jrimbault - 8 hours ago
Anglo-Saxons (in general, not all, but in particular
Americans) are so very weird when it comes to the "free
market".IMO (dirty socialist/communist that I am),
healthcare is not part of the free market. The industry
providing healthcare should be strictly regulated and no
benefits allowed.Also, what's worth healthcare compared to
the US DOD spending?
hycaria - 4 hours ago
>The industry providing healthcare should be strictly
regulated and no benefits allowed.Then how would anyone
be interested in launching such a company or working in
that industry ?
scott00 - 8 hours ago
Quite a lot actually. US defense spending in 2014 was
$614 billion, 3.5% of GDP. US healthcare spending in 2014
was estimated by the world bank as 17.1% of GDP.
icebraining - 5 hours ago
That's total spending, but even in terms of public money,
the US is at 8.3% of GDP: larger than Belgium, the UK,
Switzerland, Finland, Canada and many others.
phkahler - 7 hours ago
>> It's worth so much that a person shouldn't be required to
pay for it. Like a right.It can't be a right. That would mean
someone has an obligation to provide it. I would say it's
worth so much that a monopoly on it should not be allowed.
orbitur - 6 hours ago
If you show up in a random hospital with an injury or
disease, they are already obligated to provide care, it's
just you're directly responsible for the bill.The
individual shouldn't be paying.
thescriptkiddie - 4 hours ago
In the US it actually doesn't work this way. Hospitals
are only obligated to provide care for people whose lives
are in immediate danger. Once the patient is stabilized,
the hospital is free to kick them out. There are a
handful of exceptions and many hospitals will provide
care out of charity, but don't expect to get a half-
million dollar cancer treatment unless you have health
insurance or really good credit.
ceejayoz - 6 hours ago
> It can't be a right. That would mean someone has an
obligation to provide it.By that logic, voting can't be a
right, because someone has to register voters, run the
polling booths, count the votes, etc.
bykovich2 - 25 minutes ago
This is bonkers logic. It's wrong to coerce someone into
providing the cure, but it's right to coerce someone out of
forming a monopoly?
accountyaccount - 5 hours ago
Society has an obligation to provide it, just as it does
drinking water.
camiller - 4 hours ago
I get a water bill every month...Also, I know folks on
well water that live outside of the city, society does
not provide their drinking water.Also, There is Flint MI.
woofyman - 8 hours ago
"should Apple be the most profitable company - or someone that
literally cures cancer?"Nobody needs an Apple product. Life is
a basic need.
shallot_router - 7 hours ago
They deserve to be profitable but in a way that doesn't require
bleeding dry the cancer patients themselves.
ceejayoz - 8 hours ago
> how much is getting cured of cancer at a very young age
worth? dying vs. living another 80-90 years?A tough question,
made tougher by the side effects of doing so. $500k per
infusion pays for quite a few mostly-healthy low-income
uninsured kids to get basic pediatric care. The US healthcare
system is already priced too high for a lot of people - I pay
$2,002.25/month for my family.> should Apple be the most
profitable company - or someone that literally cures
cancer?Should healthcare really be a for-profit endeavour?
[deleted]
JoeAltmaier - 9 hours ago
From the article: "Scientists use a virus to make the genetic
changes in the T cells, raising fears about possible long-term side
effects" Is this a real risk? Is 'using a virus' in this way,
still risky at all? or is it just the word 'virus' that makes
writers put this line in every article about gene therapy?{edit:
real risk}
gumby - 9 hours ago
It's a standard tool. In fact a virus is not necessary a living
device: there's a DNA delivery wrapper (looks like. Little lunar
lander with a big spike coming out) and a payload (DNA).A virus
can't reproduce but it can inject its payload into a cell and
have the cell's DNA copy/execution capabilities copy the DNA for
the virus, making new delivery machines until the cell explodes
and emits a cloud of new dlivery agents into the organism.But if
you remove the payload and replace it with your own, that payload
presumably won't make more viruses
eatbitseveryday - 7 hours ago
> It's a standard tool. In fact a virus is not necessary a
living device: there's a DNA delivery wrapper (looks like.
Little lunar lander with a big spike coming out) and a payload
(DNA).Just a slight correction. Not all viruses look like what
you describe. [0] Others, like the HIV, are circular. [1][0]
https://en.wikipedia.org/wiki/Virus#Structure[1]
https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV
agumonkey - 7 hours ago
Virus retroviral internal machinery has been used for ages.
nerdponx - 8 hours ago
Not to be flippant, but isn't a "virus that cures cancer" exactly
how the Will Smith movie I Am Legend starts?
HillaryBriss - 6 hours ago
ok, sure, the pessimistic among us can accentuate the negative
aspects of this medical therapy, but it did solve the NYC
subway crisis. and don't forget the wildlife habitat
expansion.these things aren't all bad.
philjohn - 4 hours ago
Yes.
freeflight - 6 hours ago
> "Scientists use a virus to make the genetic changes in the T
cells, raising fears about possible long-term side effects"Isn't
that the plot of Resident Evil/Biohazard? ;)
aabaker99 - 8 hours ago
The virus is inactivated HIV. The risks about long-term side
effects pertain more to gene editing than the use of a virus as a
delivery mechanism.
jfarlow - 6 hours ago
Which are risks similar in nature to the risk of getting cancer
after one has been infected with any other virus that
integrates into one's genome.
vibrio - 3 hours ago
There is am ecosystem of many types viruses in all of us,
healthy or not. Part of that ecosystem is HERVs or Human
Endogenous Retroviruses (PERVs are the same in pigs--im not
kidding). Understanding how they do or don't cause disease is
an active area or research.
AnimalMuppet - 6 hours ago
A real risk compared to, say, dying from cancer that you already
have? What, are they worried it might give you cancer in 10
years? If the cancer you have now is going to kill you, that
still sounds like a good deal.(This is not hypothetical. My
wife's grandfather had radiation treatment for cancer. 20 years
later, he got cancer again, plausibly from the radiation. That's
still a net win of 20 years.)
Sir_Substance - 9 hours ago
A virus is a machine for replacing DNA in a cell with other DNA.
Seems like the right tool for the job.
wdbbdw - 8 hours ago
Not only are viruses a cool (if somewhat nefarious) DNA-delivery
system (though, HIV being a retrovirus probably means that it
delivered RNA instead of DNA), but it can be targeted. HIV viral
particles attack human immune cells, which just happen to be the
general cell type that needs to be treated in this case! Using
something like hepatitis or HPV probably would do the trick here
since those viruses wouldn't have the keys to unlock the doors to
get inside of the T cells.
judah - 1 hours ago
Is this the same CAR-T treatment that Juno Therapeutics tried and
scrapped[0] after 5 trial patients died after receiving the
treatment?[0]: http://www.xconomy.com/seattle/2017/03/01/after-
trial-deaths...
ksenzee - 48 minutes ago
No. From the article:> In the past, a handful of patients who
were getting similar treatments developed by other companies died
from serious brain swelling. Although those sorts of
complications did occur in some patients receiving CTL019, the
patients recovered and there were no fatalities, the company
says.
eatbitseveryday - 9 hours ago
NYTimes also covers the story
(https://www.nytimes.com/2017/07/12/health/fda-novartis-leuke...)
with more discussion about individual patients.From the NYT
article:> The panel recommended approving the treatment for B-cell
acute lymphoblastic leukemia that has resisted treatment, or
relapsed, in children and young adults aged 3 to 25.Why so young?
ceejayoz - 8 hours ago
> Why so young?It's a cancer commonly found in children.https://e
n.wikipedia.org/wiki/Acute_lymphoblastic_leukemia> Acute
lymphoblastic leukemia is seen in both children and adults; the
highest incidence is seen between ages 2 and 5 years. ALL is the
most common childhood cancer, constituting about to 30% of
cancers before age 15.
eatbitseveryday - 8 hours ago
If someone over 25 gets it, then this method is not approved
for them? That's how I read this.
ceejayoz - 8 hours ago
That's my understanding. Generally, that means they don't
have enough data on the non-approved ages from clinical
studies yet. Would make sense, given it's considered a
childhood cancer - they'd do trials on children first.
refurb - 7 hours ago
I'm guessing there were no patients over 25 in the trial?Yes,
patients older than 25 can still get it as physicians are
allowed to prescribe off-label. Whether insurance will pay
for it is another question.
HillaryBriss - 6 hours ago
i'm surprised it actually is a question. i would have
thought there was no question at all and that the answer
was just no.does anyone truly have health insurance with
benefits this high?
refurb - 5 hours ago
Insurance pays for off-label therapies all the time and
oncology it's very common.
epmaybe - 8 hours ago
you can get approval on a case by case basis, from what I
understand. The doctor or institution will have to send a
letter to the FDA beforehand though.
refurb - 5 hours ago
There is no need for physicians to inform the FDA about
off-label use. It happens thousands of times per day.
epmaybe - 4 hours ago
I think when I wrote this comment I forgot what we were
talking about. I was thinking about drugs currently being
used in clinical trials. My mistake
skadamou - 9 hours ago
A couple of things really surprised me about this article.First,
I'm sure that there is other evidence the FDA is using to
determine whether or not to grant this drug FDA approval but a 63
person drug trial seems like an exceedingly small sample size to
work with. Perhaps because this disease is so rare they could not
put together a larger trial?Also, it seemed a little bizarre for
an FDA panel to receive comments about a decision it is trying to
reach from the families of those involved in the drug trial. I
suppose there is nothing wrong with that, per se, but shouldn't
these types of decisions be reach on the basis of scientific
evidence and strive to be devoid of any kind of
sentimentality?Either way, it's always excellent to see new
cancer treatments on the market, particularly when they are as
groundbreaking as this one.
kurthr - 7 hours ago
Apparently, it's not uncommon for pharma to coach the families
that comment to the committee either... And in another orphan
drug case with small sample size, that of Sarepta/eteplirsen,
in which several evaluating scientists seem confused and the
majority were overridden (for approval) by the FDA director in
charge. Comments included, ?serious irresponsibility? (by
selectively publishing data during the whole process) and
saying that the drug was a ?scientifically elegant placebo?.htt
p://blogs.sciencemag.org/pipeline/archives/2016/09/20/sar...Thi
s new leukemia treatment is a really interesting, and perhaps
the effect size is large enough for the small trial size, but
we seem to have some problems in the review process (ignoring
data) and incentive structure (coaching parents) for these
"orphan drugs".http://blogs.sciencemag.org/pipeline/archives/20
17/05/19/im-...
ekianjo - 8 hours ago
> a 63 person drug trial seems like an exceedingly small sample
sizeSampling is basically decided on 1) recruitability and 2)
effect size. If your effect is extremely large, even with a
relatively small base size you can demonstrate the benefits of
your drug.Basically very, very large trials are mostly useful
to demonstrate benefits that are not that large to begin with.
epmaybe - 8 hours ago
It's not that small, if the statistics look good. And they
really do look better than most everything else on the
market.Also, the approval isn't for patients newly diagnosed
yet, it's only for patients that have relapsed or resistant to
current therapies. You'll see a larger phase IV trial later,
most likely.Now, off topic from your comment, I'm worried about
cost. I know that the R&D for this kind of therapy is
exceedingly high, but these therapies need to get cheaper for
us to be able to justify using them in a larger population.
sjg007 - 7 hours ago
If it works then it's certainly worth the cost. Also it is
likely that you can do donor car-T which will also reduce
costs in the future.
jlg23 - 7 hours ago
> I know that the R&D for this kind of therapy is exceedingly
highDo you have a source for that? I happen to be involved
(genetically only - my family) into medical research and
everyone I know agrees that costs are vastly inflated:*
Marketing for a new drug is not "research".* Reformulation of
trial-targets is not "research", it's re-shaping of the test
settings so you can get $drug to market ASAP.* When the
government/"the people" pay for research (through co-
operations with universities), it's not your "R&D cost".*
When you do basic research, it's incredibly easy to claim
"10k hours". Ok, but can we please claim those 10k hours only
once? Not for every variation of the substance you research
again and again?
doctoring - 4 hours ago
(I'm a physician who used to work with large pharma
companies on trial design and trial innovation.)I think the
cost of R&D in pharma that we hear about is sometimes
vastly inflated and sometimes pretty accurate, but
definitely oftentimes misapplied (especially by pharma).On
the whole, trials are expensive. Sure, there's the pre-
clinical stuff -- basic research that you're alluding to.
There's the stuff that is R&D but fails in the pipeline at
some point. There's animal studies.But in most cases, most
of the cost comes from human trials (Phase I-III, and
mostly Phase III), which can sometimes span dozens of
countries and tens of thousands of participants. For some
drugs, the Phase III trial(s) account for over 80% of the
total R&D cost. Even when they are relatively small trials
(as in this CAR-T therapy trial), the administrative and
logistical effort to implement something like this is
immense. The whole point of these trials is to collect
data, and so that data is subject to the highest amount of
scrutiny of any data in any medical enterprise. If you come
into my clinic for a pre-op before surgery and I measure
your blood pressure to be 140/85, give or take a few (oh
wait maybe I used the wrong cuff size, lemme try again, oh
it's pretty close), that's fine. But if you come into my
clinic because you're a participant on a trial for drug X,
and I measure it to be 140/85... I better be damn sure
that's right (and the study coordinator at my clinic, and
the pharma company, and the FDA), even if drug X isn't a
blood pressure drug. We've seen cases where certain
innocuous data discrepancies trigger central study monitors
(study employees) being flown out to remote clinics to
manually verify paper records or equipment logs to
confirm/reconcile errors. Inaccuracies can cause you to
miss things, or patients to be harmed, or can cause a study
or a clinic or a hospital to be shut out from performing
research again. And of course it can make the difference
between a drug approval and failure. It's a lot of
resources around the idea of data integrity.So even small
versions of these types of trials can be very
expensive.Now, is it TOO expensive? We often hear about the
cost of bringing a drug to market to be around $1B. (Some
studies have put it over $2B when you account for failed
drugs, etc.) This may or may not be right, but let's not
forget, the pharma industry makes more profit than just
about any other industry. And the way CMS and insurers
agree to pay for medicines... well, pharma has a lot of
freedom in pricing (upwards).You've hit on a lot of things
that make the release of some new drugs/devices/therapies
less expensive than we are commonly led to believe: reusing
previous data, getting new approval for a specific
enantiomer of a previously approved racemic drug, making
cosmetic updates to existing devices, the tricks go on and
on and on. And pharma keeps saying "R&D is so expensive!
This drug should definitely be 2X more expensive than the
one we're replacing." Planned obsolescence is a pain with
your smartphone; it's a lot worse with your insulin pump or
even the insulin itself! And one outcome of the high cost
of large trials is that pharma does more of these types of
un-innovation in some cases, which (due to the patent and
regulatory and reimbursement systems) simply give pharma a
free pass at making easy money off of our backs.The high
cost of trials also leads to really high prices of "true"
innovation, such as in CAR-T trials. This type of therapy
(like a lot of new oncology therapy) is highly customized,
and no longer simply some chemical compound you make in a
factory and then ship all over the world. You have to take
a patient's own cells/fluid/materials/etc, process them,
and then make modifications (in some cases unique to the
patient), and then return the processed product (to the
same patient). This is indeed highly costly on top of the
cost of performing a lengthy trial, where for certain rare
and/or terminal diseases your study endpoints are pretty
tough to capture (um, did the patient die? uh, how long do
we wait?).
jlg23 - 3 minutes ago
> most of the cost comes from human trials (Phase I-III,
and mostly Phase III), which can sometimes span dozens of
countries and tens of thousands of participantsUhm. Yes.
Again, I'd rather have an actual break down of the costs
involved here. At least in Germany insanely overpaying
doctors for conducting phase III trials replaced the [at
least] $3-4k/day budgets pharma companies had to
accommodate relevant practitioners at congresses when it
was outlawed.When the head of a public hospital in a
western country can legally triple his/her income by
conducting a study for 4h every Saturday morning, I file
the costs under marketing, not R&D.
gumby - 9 hours ago
It's an orphan indication which has special rules to promote
development. Otherwise, the thinkingngoes, nobody would
develop treatments for uncommon diseases.
bluGill - 9 hours ago
The downside of this is a treatment that you can get approved
for something rare, but now it is on the market and they can
tell doctors it has promise for some common X. Getting
approval for treating X would be more expensive because you
have to do a larger trial. (you should do a large trial for
the rare thing, but since there are not enough people with
the rare thing you cannot)
gumby - 8 hours ago
That's almost true, and is a well known part of pharma
strategy. For example Botox was initially approved for
hyperhydrosis (excessively sweaty palms and armpits) and
was used off label for its most well-known application,
wrinkles. It was finally approved for wrinkles only
recently having been approved for other things along the
way.Any MD can prescribe any (non-opiate) drug for any
indication. But the drug companies are prohibited from
doing what you say: telling docs about usages they haven't
proven in trials. Sometimes the sales rep will drop off a
scientific paper (often funded by the drug company) about
some other use of the drug -- enforcement in this area is
uneven.If they do want to advertise new uses they need to
do new trials. And though existing trial data can also be
used, if the dosage regime is different or, say the patient
pool tox risks are different (perhaps the new indication is
less serious than the orphan one) whole new tox studies may
be needed. Which seems fair.
doormatt - 5 hours ago
I'm pretty sure Botox was originally used for Strabismus.
refurb - 7 hours ago
Since the US v. Caronia decision, off-label promotion is
more complicated. The judge said restricting off-label
promotion violates the 1st amendment, as long as the
speech is "truthful"
ekianjo - 8 hours ago
> they can tell doctors it has promise for some common
XThat's not authorized, that's called "off label promotion"
and it is severly punished when discovered. Also, doctors
who use a non-approved drug for another indication can be
tracked and investigated as well if needed (conflict of
interests). Reimbursment also works only in certain
conditions and may not apply if you use the drug outside of
its allowed/approved indications.
gumby - 1 hours ago
Slight correction: as noted by others above, off label
use while extremely illegal enforcement has been eroded
and is patchy. And US law allows any MD (but not other
prescribers such as podiatrists or NPs) to prescribe any
approved drug for any medical purpose (opioids have
recently been somewhat of an exception here).However, as
you point out, insurance companies in practice have a
say. Also if the usage is implausible and there's an
adverse event I think there could be a malpractice issues
so those insurance companies also have an impact.This is
US law I'm talking about BTw.
jozzz - 8 hours ago
Isn't 25 supposedly the magic age when more cells die than are
created, i.e. when you start 'aging'.
dghughes - 6 hours ago
Then again every seven years all the cells in your body are
new so is the new you now aging faster as a "cellularly
younger" person?