
Orphan Drugs - thread_id
https://99percentinvisible.org/episode/orphan-drugs/
======
DoreenMichele
Excellent article. I had no idea that Quincy was involved in this legislation
being passed.

I would like to see more research into diet and lifestyle based approaches to
dealing with "orphan" diseases. To my mind, that's a possible path out of this
trap. You have to eat anyway. Food chemistry can have substantial impact on
the body, especially if you have some anomaly where the body processes certain
molecules differently.

I manage my condition with diet and lifestyle. I get attacked and dismissed as
a deluded nutter suffering Munchausen for trying to talk about that online.
But I don't know what the hell else to do.

The mods on HN have been really great about the situation. I've been thrown
off of other forums or told that people violating forum rules to attack me are
fine and I'm the problem and I just need to shut up. I try to not push it too
much because I don't want to end up locked up in an insane asylum and dead
because of it, like Semmelweis.* Though, in my case, dying would most likely
be due to being denied the control over my diet and physical environment that
makes it possible for me to be drug free and relatively healthy rather than
being beaten by the guards and ending up with sepsis.

You probably can't make the kind of money from researching and promoting
dietary and lifestyle approaches to such conditions that you can from orphan
drugs. I don't personally know how to monetize it at all. When I had affiliate
links on my health blog for a particular brand of salt I got attacked for that
and told I could not be trusted, I was merely trying to get rich off the
suffering of sick people. Having a form of the condition myself hasn't served
to give me any credibility.

In the minds of most people, the real definition of CF is what my CF
specialist once told me: "People like you don't get well." Since I'm getting
well, clearly, I'm a liar who doesn't really have CF.

I don't know how to find a path forward. Maybe the answer is someday I say
"Fuck this noise" and stop trying to share what I know and just focus on
something that pays my damn bills. But, for now, that idea still rankles.

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

~~~
jnovek
To me, it's not beyond reason that cycstic fibrosis would respond to diet and
lifestyle, and is an understudied phenomenon. I see potential rational
caveats, and my guess is that these caveats create some jerky knees among
other people who are also suffering (and I'm sure, as a sufferer, you know how
emotional the experience dismissal is). A few hypotheses:

    
    
      - CF responds to diet and lifestyle in some poeple but not others.
      - Time spent with the disease and disease progression is a factor on how well it can be managed without medication.
      - The above things you mentioned (e.g. you actually have another mimicking condition).  If it's something like that, I think you are still operating on good faith and you shouldn't be blown off by other CF sufferers for it... but people are irrational.  Don't confuse this with denial, by the way!  It's simply a rational possibility.
      - The exact *features* of diet and exercise that affect CF aren't well studied/understood and your regiment randomly hits on them.  This reminds me of people who feel better eating gluten free that don't have celiac -- eating gluten free is a diet that happens to incidentally eliminate a lot of other food allergens other than gluten.  That is, you have a false solution to the problem with real solution hiding in it.
    

In any case, I've been on the "haters" side re: diet and lifestyle preaching
so I can empathize there, too. In particular with chronic migraine, there is a
granola crowd who has barely suffered an ailment in their life who suggest
that "perhaps a better diet and yoga will help". I've reached a point where I
want to slap them sometimes; one of my migraine prodrome symtoms is irraional
anger and anxiety, perhaps I will someday :-P

Personally, I wish you the best of luck. I suspect it's statistically likely
that you'll depend on pharmacutical intervention _someday_ , hopefully, you
can delay that is long as possible. I am by no means anti-pharmacutical, but I
know from experience that maintaining a long-term drug regiment has it's own
problems.

Fuck chronic illness, raise your hand if you're tired of telling people that
your illness won't go away, it can only be "managed". Feel as well as you can.

~~~
DoreenMichele
Thank you.

 _CF responds to diet and lifestyle in some poeple but not others._

I believe there are around 1600 known alleles -- last I checked. That number
may have changed. I am no longer on any CF lists. It's too much drama.

Anyway, the mechanism for CF is a defective cell channel. There are various
ways the cell channel can be defective. In some variations, it's outright
missing.

To my mind, this is sort of like the difference between albinism and being
Caucasian. If you don't have the channel at all, I think that's a completely
different and more serious problem than if you have the cell channel, but it's
wonky in one of a variety of ways.

 _Time spent with the disease and disease progression is a factor on how well
it can be managed without medication._

This makes it very complicated to talk about. CF causes a compromised immune
system and malabsorption. I think most of what most people think of as CF is
really severe and chronic malnourishment combined with chronic infection.
Those pieces need to be redressed to get healthier. Once redressed, it's
vastly easier to manage.

If you are Caucasian, you are at greater risk of sun burn and skin cancer.
Imagine a society that called being Caucasian _Pale Skin Disorder_ and
dismissed the idea that protecting yourself from the sun mattered. This
society lives in, say, Hawaii where the Tropical sun is particularly intense
and everyone lives in bathing suits. People with Pale Skin Disorder are
chronically severely sunburned. Being chronically severely sunburned has a
long list of secondary and tertiary problems associated with it, including
high rates of death from skin cancer at an early age.

Someone comes along and says that putting on more clothes or moving someplace
where the sun is less harsh can clear up most of those symptoms and give you a
nearly normal life with the proviso that even elsewhere you should take
reasonable precautions.

Everyone laughs and says "Dumb bitch! Putting on more clothes won't cure
cancer!"

 _The above things you mentioned (e.g. you actually have another mimicking
condition). If it 's something like that, I think you are still operating on
good faith and you shouldn't be blown off by other CF sufferers for it... but
people are irrational. Don't confuse this with denial, by the way! It's simply
a rational possibility._

My official diagnosis is _atypical cystic fibrosis._ I've had two or three
blood tests for the 100 most common alleles. I don't have any of those.

My doctor requested a more comprehensive and expensive test from Stanford. My
insurance company denied the request. They had probably already spent at least
$25k on me that year according to conversations I had with my sister who had
serious health problems of a different sort, civilian insurance and she works
at the CDC. I was a military wife. I saw damn few bills. I mostly flashed my
ID card and got it for free.

My doctor diagnosed me on the basis of symptoms and medical history. Based on
my lifelong history of respiratory infections etc, he expressed surprise that
it took so long to get a diagnosis. He felt the diagnosis was correct because
I was responding to treatment.

I was previously misdiagnosed as asthmatic. Articles I've read indicate this
is a common misdiagnosis for people with atypical CF, who tend to be treated
like a hypochondriac and not get identified until late in life. In a nutshell,
that's my story.

My best understanding is that I have all the same issues as someone with
classical CF, they are just less severe. So most likely the channel defect I
have is relatively moderate.

The fact that I can't name my alleles because my insurance company denied the
request for the more comprehensive test is one of the reasons I have no
credibility on CF lists. Everyone with CF can name their alleles. Except me.
So I must be a fake.

 _The exact features of diet and exercise that affect CF aren 't well
studied/understood and your regiment randomly hits on them. This reminds me of
people who feel better eating gluten free that don't have celiac -- eating
gluten free is a diet that happens to incidentally eliminate a lot of other
food allergens other than gluten. That is, you have a false solution to the
problem with real solution hiding in it._

Well, I kind of randomly stumbled across stuff that helped, then tried to
figure out why it helped. Having a diagnosis of CF was enormously helpful in
figuring out why it helped and building on my successes. At this point, I
think it's very unlikely that it's "coincidence" that it helps, but really due
to some other dynamic.

One example: I used to take $300/mo in supplements. Given my diagnosis and the
thousands of dollars a month most people seem to spend on maintenance drugs, I
figured that would continue for life. Instead of maintenance drugs, I would
have maintenance supplements.

I don't take supplements anymore. I think redressing the severe malnourishment
reversed a lot of my symptoms. I also think that _the normal progression of
CF_ is rooted in a vicious cycle where chemical derangement of the cell
promotes more misfolds of the CFTR. So, the sicker you get, the fewer CFTR
channels you have at all. The bottleneck gets narrower and narrower and
narrower. The sicker you get, the sicker you get.

Reversing the cell chemistry derangement stops that vicious cycle. I can
optimize the number of semifunctional CFTR channels I have, widening the
bottleneck.

This is known to help. Some drugs help by increasing the number of CFTR
channels you have.

There's actually a fair amount of well known stuff that helps. It's just
piecemeal and not promoted by doctors as standard therapy. It gets downplayed.

One thing known to help is MCT oil. This is oil high in medium chain
triglycerides. It's typically from Palm oil or coconut oil.

MCT oil or coconut oil is well established as therapeutic for people with
serious gut issues, not just CF. I once found medical literature online where
it used to be prescribed by doctors for various issues, including stomach
cancer.

They frequently prescribe ADEKs, a vitamin containing A, D, E and K. These are
all fat soluble vitamins. People with CF are typically chronically short on
such vitamins.

(IIRC, ADEKs was actually discontinued. Presumably, there's not enough money
in it and it's just a vitamin supplement.)

So we already know people with CF significantly misprocess dietary fats and
this has significant health consequences. We just haven't pursued that in
earnest as a serious therapeutic approach, probably in part because we don't
take diet as seriously as we do prescription drugs and in part because there's
no money in giving people a list of beneficial foods and a list of foods to
avoid.

One of the most significant changes I made was eliminating peanut oil from my
diet. After five years of trying to avoid all peanut products, I was able to
reintroduce peanut products back into my diet in small quantities,
occasionally. I have to buy the "natural" peanut butter. I can't buy the
regular peanut butter. I still avoid peanut oil.

I grew up in Georgia, peanut capital of the known galaxy. A lot of American
snack foods are made with peanut oil. Chick-fil-A proudly advertises they use
only 100% peanut oil. That was one of my ex husband's favorite eateries. I
will not set foot in a Chik-fil-a anymore. Even drinking lemonade or eating
salad from there tears up my gut because everything from the place is coated
with residue from them cooking on high heat with peanut oil.

------
plmu
Another sign that health care and commerce do not mix.

In some countries, there are plans to "regulate", in this case to mandate
distributors to keep 4 months of supply. I doubt if that will work.

Instead, like the UK NHS, where the healthcare itself is non-commercial and
fair to everyone, the R&D + production of drugs could also be organized much
better:

Do the R&D via universities, that should receive grants to develop into
directions that are socially wanted, instead of developing more of the same
(like high-bloodpressure drugs) just because of commercial interests.

States can collaborate and organize e.g. very expensive high engergy physics
R&D (such as CERN) or fusion energy. Why would the same system not work for
drugs R&D?

The production itself, completely patent free, can be granted according to
demand to commercial companies. These just produce what health care systems
order. The states/systems pay a fair price allowing the companies to have a
decent profit margin to remain viable, but the current profit margins in the
pharma sector are much too high and immoral, since there are people dying
because they cannot affort the necessary drugs.

I think this sector has proven more than once, that it is not capable of
taking the very high responsbility, but is driven by greed that leads to
immoral actions.

~~~
AllegedAlec
You're severely underestimating how expensive drug research is. It costs
nearly 3 billion dollars to get a drug from zero to market-ready according to
the TCSDD.

~~~
gomox
This often quoted number includes the investments in failed drugs (an
outstanding majority) and 1.5B of an 11% cost of capital "opportunity cost"
(i.e. money not gained by investing in other stuff).

It is therefore highly misleading when quoted out of context, as it is not the
real amount of money that is spent on a single drug.

~~~
refurb
Huh? Those two things certainly do represent real costs.

If a company spends $2B to develop 5 candidate drugs and four fail, the cost
was $2B for that drug. Learning what doesn’t work helps you find something
that does.

Second, opportunity costs are real costs, even though most consumers ignore
them. You see this when buying a home. People never count the money they could
have made by putting their down payment into the market, but that’s still
money lost. You can argue 11% is too high, but that’s a different argument.

~~~
gomox
I understand the numbers, but they are highly misleading, which is my point.

When you say it costs $X to do $Y, including in $X the cost of 20 other times
you fail to do some other thing that isn't $Y is unexpected.

Likewise re: opportunity costs. The actual investment doesn't include the
opportunity cost. I.e. only around half of that money had to be obtained.

The numbers are meaningful from the capital allocator perspective, which is
not the conventional perspective.

The number that people picture when you say "the cost of bringing a drug to
market" is ballpark 100-200M.

~~~
rebuilder
The conventional perspective seems misleading, then. Saying you can bring a
drug to market for a price that doesn't include the costs of failure in
finding out how to make the drug in the first place completely distorts the
matter, IMO.

Maybe I'm not getting what you think the benefits of not counting research
costs across the board are.

~~~
newtonic
Pharmaceutical development is really just throwing mud at a wall and seeing
what sticks.

Sometimes, something sticks and you get rich, sometimes it doesn't and you get
nothing.

If during one of those failed attempts you came across something useful but
not lucrative, I think the cost of bringing it to market should start at that
point, and should not include all the trials when you were looking for the
cash cow that you had to do anyway. _shrug_

------
riffraff
This is very interesting but it lacks a key piece of information: how is this
situation handled in other countries?

~~~
ekianjo
In Japan orphan drugs get priority reviews and patients don't pay anything
(i.e. government/social security pays 100% for the rare disease). Companies
who produce such drugs have almost carte blanche to make any price they want,
since "nobody" is directly paying in the end.

~~~
lovemenot
>> Companies who produce such drugs have almost carte blanche to make any
price they want

That's not really right since it's not open competition.

MHLW sets a price for orphan drugs, which all companies must follow. In
practice, the Ministry tends to use global prices as baseline in its
negotiations with orphan drug suppliers, through their trade group
representatives.

------
DennisAleynikov
this is an awesome look into the economics of curing diseases that cannot
benefit from economies of scale. Its unfortunate the rare diseases end up
having such expensive cures but on the other hand people can develop cures for
disease that otherwise would be uncurable.

interesting double edged sword

------
matt_the_bass
This discussion is Great! Clearly this is a difficult topic that lots of
people feel is important. I find it interesting that there is so little
consensus in the comments. To me that is a really interesting question and
discussion.

I wish I had a good answer.

------
ekianjo
> one rare disease drug came out with a price tag of $150,000 a year — a lot
> of money.

If there are just 100 patients out there that's not a lot of money for the
company in the end. Cancer drugs are way more common and yet remain expensive,
too.

~~~
hrktb
For orphaned drugs, companies have a monopoly status on it and clients
litteraly can’t forgo buying, and will do whatever research is needed to find
the product. There is no nudging or bribing the doctor or whatever is needed
to take an edge.

Considering it’s long argued that one of the main cost of a drug is marketing
[0], for any drug where it’s significantly more than 100 people we shoudn’t
get these crazy prices.

[0] [http://naturalsociety.com/research-development-new-drugs-
not...](http://naturalsociety.com/research-development-new-drugs-not-paying-
off-6321/)

~~~
ekianjo
You are missing a major point. Lots of people who have rare disease are not
even aware they have them, or not even diagnosed because their local doctor
has never seen it before and mistook it for something else.

So yes, you still need "marketing" to spread awareness for rare diseases,
because they are, well, rare.

~~~
techbio
Yet the CDC is effective at spreading awareness of common diseases. Why do
this via drug marketing?

------
based2
[https://www.eurordis.org/en](https://www.eurordis.org/en)

