Prompted by the recent barrage of advertisements related to new prescription drug offerings from a myriad of pharmaceutical companies promising a cure for plaque psoriasis.
Not to obsess about plaque psoriasis, for one could substitute any number of other ailments ranging from toe fungus to cancer,
but plaque psoriasis is currently the rage in offerings from “big pharma”. Knowing that the pharmaceutical business is a highly secretive endeavor:
How in the heck do multiple companies simultaneously develop independent cures for a specific disease, and somehow manage to release and market them… all at the same time? Not to diminish the import of plaque psoriasis to those who suffer it, but it is difficult for me to believe that a relatively obscure (1%-2% in the US) non-life threatening disease could somehow, magically, be focused upon by all of big pharma.
Over and over again, just insert your favorite ailment. It is impossible for the Moon & stars to align this often, so what’s going on?
Because it was generally known which interleukin to target to ameliorate psoriasis symptoms. So all pharma companies were starting with the same info. They are all variations on a theme.
Also since psoriasis is an auto-immune disease, research into it pays multiple dividends as some of the research steers them into treatments for other auto-immune problems. So they get more bang for the buck.
Note these are treatments, not cures. Stop the treatment and the conditions return.
Big Pharma companies are secretive, but academic research isn’t and that’s usually what starts the ball rolling. Academic research lives on its publication record (funding often depends on publications, and cites of those publications, hence cite boosting and … but that’s another story).
So typically a “target” is discovered in academic research and published (it would the role of a specific interleukin in the disease process in this case, if I understand BwanaBob). The good targets set off a feeding frenzy, with pharma companies falling over themselves to investigate potential and then develop products based on said target. Then its a footrace to market, which is why multiple “similar” products arrive over a relatively short period.
It sounds like a great deal of the research necessary in developing new drugs for any given ailment is performed independent of, and prior to, the pharma industry’s involvement. They fail to mention this in their commercials.
Why would they? If they have 30 seconds to advertise a medication, why would they spend several seconds mentioning that?
And it’s not relevant in any event; it’s more like if a researcher in a university published a paper detailing how a specific catalyst might be used to get 100 mpg in a certain type of engine.
You’d see ALL the car makers coming out with their variants on that in short order- they’d all be patented, and all would be sufficiently different to avoid encroaching on each others’ patents. Drug manufacturing is no different.
As I understand it, a lot of the time, the real difficulty isn’t necessarily always in identifying compounds with therapeutic uses, but rather it’s in developing the production process to produce said compounds with a sufficient level of purity and in an economical manner.
It’s rarely the second thing in pharma - it’s the first. The process and production chemistry (or biology) of the compound is demanding, expert work, but still not in the same league of difficulty, expense, and risk as developing a medicine that is safe and efficacious for human use.
You also have a lot of flexibility with the cost of goods - you could be working with a molecule that is dosed in the microgram regime and will be sold for a lot of money, which gives you a lot more latitude in route design and process.
Some complex medicines available now, mind, which do place a huge challenge on production - stuff like antibody drug conjugates are very demanding to produce on scale. But they are exceptional.
It’s a different story in less lucrative markets - agrochemistry, say, where you might need to make something used on the ton scale, sold for not much money. Far more constrained in your process chemistry and need some really creative approaches to get a financially viable process route together.
I’m a chemist myself and have spoken to a few polymer / coatings groups over the years about doing stuff - they’ve tended to be short conversations. *We’d like a new alkene functionalisation for this class of primer used to paint ships - substrate, solvent and catalyst need to be completely environmentally innocuous and cost 20 pence per kilo all in.
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Full disclosure comes to mind. In this day and age, with people in the U.S. calling the industry out concerning price gouging, the pharma interests must be feeling the heat and have produced quite a few commercials that don’t push any particular drug, just themselves as an entity. Surely you’ve seen them. They always dwell on how hard their jobs are, how dedicated their employees are (working 24-7 just for us!), and how much money it costs for research. The takeaway I get from these ads is in the form of a veiled threat, whereas: “If politicians mess with us (regulate), we will stop producing drugs that save lives.”
Perhaps if they wish to put forth the notion of themselves investing every spare nickel into research and therefore are operating on a shoestring budget, they should be required to divulge that the base concept/research for any given drug was provided free by others as mentioned upthread. Such requirements are why pharma must now spend approximately 50% of their advertising time delineating adverse side effects etc. They don’t do this because they want to…they do it because Federal regulation says they have to. It appears they can afford it.
This is way off the original topic, but: it’s not that simple, of course. Here are a couple of articles (one UK and one US) explaining the increasing trend for early research in universities to be funded by … Pharma companies. Makes sense all round, pretty much, I guess, but I assume this must limit the independence of universities to publish. Hey, it’s a new funding model, and academic ideals cost money.
The drugs you mentioned in the OP, assuming they are new chemical entities (I don’t know the disease area at all) are a decade or so on from the earliest developmental work - it was a rather different world back then.
Yes, it’s not simple, but not off topic. The drug I referred to in the OP was a RECENT development, but not exclusive, and not intended to preclude others that were developed recently.
Nonetheless, how was it a “rather different world back then”?
Different in that the method of funding university research into the fundamentals of disease processes is changing. And over the period of time it takes to develop a drug to market - let’s say ten years - we may see it change to a remarkable extent, with these university departments shifting from essentially independent and funded by grants* to being more-or-less satellite units of pharma companies. Twenty years ago, working for a pharma company, I used to fairly routinely mingle with academics on a kind of peer-to-peer basis. You could chat to them about what was going on. I imagine that would be a very different relationship these days.
I take your point that Big Pharma neither deserves nor needs a free ride (at least, I think that was one of the points that you were making); but as it increasingly pays its way in universities, it must be changing the way they work, the work they are permitted to do, what they are able to publish…
A different world.
j
but make no mistake, that’s a dirty and cut-throat business in its own right.
Depending on how you account for the cost of capital it takes between $1.4 and $2.7 billion dollars to get a drug to market. Why would it matter whether that cost includes all the research or just part of it?
Well, I suppose it depends what one’s perspective is on how one “accounts” for costs. From the numbers you provide, there is a significant variance between 1.4 and 2.7 billion dollars per drug to market. Let’s call it a factor of two. Since pharma chooses to use research cost as the primary reason for their inflated retail prices to market in the U.S., it is not unreasonable to question how much of their research is subsidized by U.S. taxpayers, perhaps by a factor of two.
Boy, can I answer this question. I’m currently starting up my own company (in this field) around a novel therapeutic that nobody else is targeting here.
The answer to your question is that it’s hard. I spent ten years in the lab generating data around this target before I was able to convince people to invest in the idea. And “invest” means put it into clinical development. The bill for that investment is about 50 million and counting so far, and I’m not even to phase II. And, then the company changed hands and decided not to do this anymore, so I’m taking it with me and starting a company.
If I were starting a company around a nuance of something that everybody else was doing, I could go to investors and the story would be simple. But, I’m going to investors and have to tell them an entirely new story. These folks are generally pretty savvy scientifically, but they are not really in the trenches scientists (if they have a science background at all). And, ultimately this is a business decision; if I’m asking for 50 million and to develop a molecule around an established pathway there is less risk to them that it won’t work at all. But, I’m asking for 50 million around a pathway that I discovered and that’s a harder sell because they are, to some extent, investing in me.
That’s the high level view. If you have specific questions, I can answer them (but will still try to maintain some anonymity…)
First off, Chapeau! - and the very best of luck to you.
Secondly - and I do not mean this to be in any way a cause of awkwardness - but some people are going to look at this and say, Hang on, fifty million versus 2.7 billion - what gives? And it’s a reasonable question. Do you feel able/happy to expand?
Well, I need to raise 50 million in order to get into Phase II. But, I’ve already spent somewhere around 50-70 million because this has already been through preclinical and phase I, and will probably cost an additional 50-70 million to finish phase II depending on how it is designed. The 50 million number was the number I’m seeking in series A financing in order to get started. So, getting through phase II is easily going to run up a 200 million dollar tab ultimately.
And that’s just phase II. Phase III is where the real money is spent. It will easily get over 1B, and a lot more depending on the disease that we ultimately go after in phase III. But, to be honest, I don’t have the interest or stamina for that (phase III bores the hell out of me), so in all likelihood, upon phase II success I would either partner with someone else, or sell it outright.
But, remember, most drugs fail. So, I’m asking for people to invest tens of millions of dollars, and they know that the likelihood is that they will lose all of it.
Barring actual data from the OP, it’s hard to fight past confirmation bias. But for plaque psoriasis, it’s true that there have been 10 new approvals since 2014. Out of 240.
Seven of these (risankizumab-rzaa, tildrakizumab, certolizumab pegol, guselkumab, brodalumab, ixekizumab, secukinumab) are monoclonal antibodies*, I think mostly doing antibody things to interleukin 17A and 23, although I didn’t actually check them all. Secukinumab (“Cosentyx”) was the first, approved in 2015. The results of the phase I trial were published in 2010. The protein was discovered in rats in 1993. It takes a while to recognize something as a therapeutic target and, specifically, one you use antibodies on. If that early research is public, then individual companies are free to start pursuing it on their own. It takes a while. But if they start around the same time, we’ll expect to see similarly-timed approvals for those few that make it through
*Comment from the peanut gallery: “See the “-mab” suffix?” The more you know.
Likewise, we just saw three CGRP inhibitors approved for treating migraines. I think all in the same year. Monoclonal antibodies are hot. There have been four approved thus far this year, 10 last year, and 12 in 2017.
So that’s why we’re seeing the rash of plaque psoriasis approvals. But I encourage the OP to find some actual examples from the last few years to support this “again and again” claim.
Phase 0 - is really what I knew as early phase I
Phase I is basically safety testing, to see if this drug is safe in humans at a useful dose
Phase II is proof of concept - does the drug show evidence of having the effect we think it should have
Phase III is confirmatory clinical trials
(Phase IV is post marketing safety monitoring)
Phase III is stunningly expensive. It’s pretty common practice for drugs that have survived through Phase II to be sold or licenced to an organisation that can afford to fund Phase III. To return to your original line of questioning gogogophers, it would not be unusual for a drug currently in development to be based on original university research (for which the uni is maybe paid a licensing fee); developed through Phase I by the uni and a partner; picked up at the end of Phase I and taken through Phase II by another organisation, and then licensed on again for Phase III development. In the most extreme example I have seen, I worked on a drug where so many of the groups involved had a financial interest through licencing agreements that (I was told) it wasn’t financially feasible to develop the drug further.
Hepatitis-C and Psoriatic Arthritis come to mind.
The OP was put forth based upon my casual observation as a consumer exposed to pharma advertisements. I’m unable to provide any scientifically irrefutable “data” for you.
Hi Ruken. Are you unconvinced that new similar products come in waves, as gogogophers claims? It’s well known - they are generally referred to as Me-Too products, and here’s a paper discussing the phenomenon and giving examples. Note the first para of the introduction: