How pharmaceutical industry financial modelers think about rare diseases • Hacker News Board

Re: How pharmaceutical industry financial modelers think about rare diseases

#91

Post by jessriedel » Tue, Apr 30, 2019, 6:22 PM UTC

SirLuxuryYacht wrote: post #78

gumby wrote: post #38

Having been through the early phases of this (both as bench scientist and management, up through Phase II) I can say that this author's analysis is right on. There is a macro wrinkle he doesn't mention and that makes things worse: as we increasingly succeed on stopping the big killers (e.g. lung cancer, CIs, various accidents that constituted most of the causes of death into the 1990s) the histogram of death starts t…

> histogram of death Not something you read everyday! How does your "wrinkle" make things necessarily worse? All [men] must die (sorry) at some point so succeeding at removing the biggest killers would give more people a second chance to die of something else later. Just because we cure cancer won't mean that there are suddenly more causes of death, just that the people who would have died from cancer will die of a v…

> How does your "wrinkle" make things necessarily worse?

If a small number of causes continued to be responsible for a large fraction of all deaths even as causes were defeated/delayed by medical interventions, then a continuous application of research resources could plausibly lead to consistent increases in life expectancy. For instance, if as heart disease deaths are being reduced by endovascular procedures those people are dying mostly of colon cancer, then we could divert resources to colon cancer research and hope for continued progress. But if, once the major diseases are suppressed, the number of causes of death explodes into a diverse spectrum of unique illnesses, there is little hope that constant (or reasonably increasing) resources can do much.

Re: How pharmaceutical industry financial modelers think about rare diseases

#92

Post by Balgair » Tue, Apr 30, 2019, 6:25 PM UTC

dralley wrote: post #81

dcx wrote: post #42

This is an impressive article and an impressive couple. From the site's about page: My name is Eric Vallabh Minikel and I’m on a lifelong quest to develop a treatment or cure for human prion diseases. I originally trained as a city planner at M.I.T. and was working as a software engineer and data analyst in the transportation sector when, in December 2011, I got some bad news. My wife and the love of my life, Sonia V…

>For example they switched him to a ketogenic diet back when this was just starting to show results for cancer I'm curious as to how this would have an impact. Is there any research demonstrating that keto slows the development of cancer? Or hypotheses on why that would be the case?

Though it's incredibly dependent on the type of cancer, it's history, it's environment, and it's genome, it is related to the metabolic pathway that you shut off.

This is known as the Warberg Effect [0]. Essentially, for some reason, some cancers will start eating only via glycolysis and not via oxidative phosphorylation. Glycolysis requires glucose (sugars, like carbohydrates), so if you just stop eating foods that turn into glucose, those types of cancers will starve. Low sugar diets are ketogenic diets.

I'll be clear here, this is super speculative. Cancer isn't something like measles, each one is super specific to the organism and evolves over time. Keto diets may work for a while to harm cancers, but may also select for more 'hearty' cancers over time. It's not very well understood, even still.

[0] https://en.wikipedia.org/wiki/Warburg_effect_(oncology)

Re: How pharmaceutical industry financial modelers think about rare diseases

#93

Post by jonlucc » Tue, Apr 30, 2019, 6:32 PM UTC

iandanforth wrote: post #67

This is a well researched, informative and infuriating article. Within the system I cannot think of a better or more determined approach to this problem, but as this is HN I need to lay out a few points. As we mint more billionaires they are going to do an end-run around the FDA. If I were a billionaire there is no way in hell I'd wait for a standard drug trial to progress on an FDA timeline. Eventually one or more o…

> If I were a billionaire there is no way in hell I'd wait for a standard drug trial to progress on an FDA timeline.

You don't have to be a billionaire for this. There aren't many drugs which sit between proving efficacy in clinical trials and FDA approval, and ones that are like that only sit there for a few months. Of course, those could be important months for a particular patient, but there are ways to handle this. One such program is called "compassionate use". The idea is that if you have no other hope, you can be prescribed a non-approved treatment.

There aren't as many potholes in this as you seem to believe. Drugs which are proven efficacious and safe usually are submitted for approval, because it's expensive to run trials. It wouldn't be the first time a billionaire decided to do something medically unwarranted or ambiguous, but that doesn't mean it will become a norm.

Re: How pharmaceutical industry financial modelers think about rare diseases

#94

Post by jonlucc » Tue, Apr 30, 2019, 6:34 PM UTC

physics137 wrote: post #47

ekianjo wrote: post #19

Earlier quoted context omitted.

That's more than what most PHD produce in their careers (in terms of go to market).

Sure, in large part because "going to market" is not the primary objective of many PhDs.

It's still very fruitful compared to PhDs in terms of the pharma industry.

Re: How pharmaceutical industry financial modelers think about rare diseases

#95

Post by jonlucc » Tue, Apr 30, 2019, 6:37 PM UTC

vibrio wrote: post #79

refurb wrote: post #34

Earlier quoted context omitted.

There is much wrong with the pharmaceutical industry including pay-to-delay generic I disagree on this one. Pay-to-delay is just the branded drug manufacturer and the generic company splitting the difference through negotiation. What you end up with something in-between the two potential outcomes. Situation: branded drug has 2 more years of patent life, but generic company wants to challenge it; neither party is sure…

If the patent is invalidated, then what provides the generic company with exclusivity for two years-- I thought the regulatory exclusivity provided to first-in generics was only 6 months?

I'm not at all an expert on generics, but the company suing to remove exclusivity has almost certainly done some groundwork needed to produce the generic drug. They likely need to figure out how to produce the drug as well as some business stuff like market determination, so a second generic manufacturer is probably a bit behind.

Re: How pharmaceutical industry financial modelers think about rare diseases

#96

Post by vibrio » Tue, Apr 30, 2019, 6:51 PM UTC

jonlucc wrote: post #95

vibrio wrote: post #79

Earlier quoted context omitted.

If the patent is invalidated, then what provides the generic company with exclusivity for two years-- I thought the regulatory exclusivity provided to first-in generics was only 6 months?

I'm not at all an expert on generics, but the company suing to remove exclusivity has almost certainly done some groundwork needed to produce the generic drug. They likely need to figure out how to produce the drug as well as some business stuff like market determination, so a second generic manufacturer is probably a bit behind.

for significant small molecule drugs, there is commonly a cohort of generic firms ready at expiry. There is usually little barrier to entry beyond the patent or regulatory exclusivities. Prices are typically crushed after the 6 months. Biologics (antibodies/ vaccines) are a different story because of the complexity of their manufacturing and characterization.

Re: How pharmaceutical industry financial modelers think about rare diseases

#97

Post by vibrio » Tue, Apr 30, 2019, 6:54 PM UTC

refurb wrote: post #88

pmyteh wrote: post #73

Earlier quoted context omitted.

> Everybody gets something from the deal Everyone except the patient, who continues to pay the exclusivity premium but would (assuming option 2) have paid less.

But you don't know option 2 would have been the outcome. Rather than both companies duking it out in court for a few years, the patient benefits when the generic entry happens quicker than if the patent held.

I guess the concern is that paying a company not to challenge the patent(and start the 6 month clock if the patent is lost) is anti-competitive and collusive.

Re: How pharmaceutical industry financial modelers think about rare diseases

#98

Post by robocat » Tue, Apr 30, 2019, 7:05 PM UTC

refurb wrote: post #49

csunbird wrote: post #11

Earlier quoted context omitted.

I agree completely, most people overlook the "opportunity cost" of investments. If an investment makes %3 per year but you could invest in something else that makes %4 per year, while you did make profit, you actually lost money, because you missed an opportunity to make an extra revenue equals to %1 of your money (or %33 more profit).

You see people do this a lot with housing. They make $100k after 5 years and pat themselves on the back. They ignore that if they had put their down payment in the market, they would have made $110k.

Your summary is missing a critical factor: you probably need somewhere to live. Let's simplify that to the binary choice of rent or buy, so now your decision is: what is the risks and rewards for my "portfolio" after X years renting versus after X years buying.

For your incomplete example, if the summed cost of rentals was $10k higher than cost of owning the home, then they made a profit.

Re: How pharmaceutical industry financial modelers think about rare diseases

#99

Post by btown » Tue, Apr 30, 2019, 7:13 PM UTC

golergka wrote: post #24

btown wrote: post #4

This article does a good job showing how big an impact the concept of "time value of money" can have on a multi-year investment of any kind - pharmaceutical or not. (Particularly since many of us in software are effectively investing nontrivial amounts of our salary in illiquid investments.) I'd imagine that many tend to think of a $X investment as a $X investment... but if that investor could get effectively compoun…

The more I learn about finance, and the better I grok money, the more I start to think of money as a substance that represents time-travel, in a sense. Current amount of money you have on your account is always tied up to your past decisions or to a space of your possible decisions about it, and so well-quantified, that the worth of basically anything is always tied up to a dynamic process which is always, in the end…

In certain ways the entire concept of retirement saving is an investment in the ability to time travel later in life!

Re: How pharmaceutical industry financial modelers think about rare diseases

#100

Post by bluGill » Tue, Apr 30, 2019, 7:13 PM UTC

selimthegrim wrote: post #80

chadash wrote: post #10

I was surprised that this article didn't mention the Orphan Drug Act of 1983, which was passed by congress to facilitate the development of drugs for rare diseases (many other countries have similar legislation). This act gives tax incentives, subsidies, lowers clinical trial requirements and increases exclusivity for the development of "orphan drugs", which otherwise might not be economically viable to develop. That…

Avik Roy has an absolutely blood-boiling section of this report devoted to ways companies are gaming the Orphan Drug Act https://docs.house.gov/meetings/GO/GO00/20190129/108817/HHRG...

Not really. While he makes it sound bad, what is happening is that in exchange for actually proving that drugs we "know work" actually work companies get a monopoly for a short time. I'm glad some of the treatments doctors have been using for years now have science behind them so we know more about how well they work.