Dr. Derek Lowe, from In the Pipeline, writes:
So since drug pricing and FDA regulations are so much in the news, it would seem like the perfect time for a small company to game the system for big profits, right? That's apparently what Marathon Pharmaceuticals believes. They just got approval for deflazacort, a steroid, as a treatment for Duchenne Muscular Dystrophy.
[...] So what's not to like? Well, this drug has been around since the early 1990s. Marathon most certainly did not invent it. Nor did they think of applying it to DMD patients – the biggest clinical trial of the drug for that indication was done over twenty years ago, by someone else. DMD patients in the US were already taking the (unapproved) drug by importing it from Canada. Marathon just dug through the data again and ran a trial in 29 patients themselves, from what I can see. I should note that this is not any sort of cure, nor does it address the underlying pathology of the disease. The steroid treatment makes muscle strength in DMD patients stronger – barely. But even for that benefit, US patients will now have to get it from Marathon at something like 50 to 100 times the former price.
[...] So while I defend the FDA's function of making it tough on new drugs (making them prove safety and efficacy), I cannot stand how loose they are with old generic compounds. The agency hands out extremely valuable rewards like lollipops in these cases – a priority review voucher can be sold for hundreds of millions of dollars
[...] And they're also allowing the likes of Marathon to make the rest of the drug industry look like greedy sociopaths. Marathon, Catalyst, T*ring and all the rest of the people who are pulling these tricks have the word "Pharmaceuticals" in their name, but they are not drug companies. They discover nothing. They do no research. They take virtually no risks. They exist only to play legal games and watch the money roll in.
[...] As for the FDA, the agency probably can't change this on its own, though, even if it wants to – Congress has to act to give them the authority to deny market exclusivity or priority review vouchers under some conditions. Either that, or we should rethink these incentives entirely, because they are (clearly) too easy to exploit for fast bucks.
Also at ArsTechnica.
Dr. Lowe, from In the Pipeline, writes an update on a story we covered earlier this year:
You may recall Marathon Pharmaceuticals, the small company that announced plans to sell a long-used steroid treatment (Emflaza, deflazacort) in the US to Duchenne muscular dystrophy patients. The price was set to go up steeply, since the company was awarded years of market exclusivity by the FDA (under their program to reward orphan-drug indications like this one).
This business model is the same one followed by a number of other small outfits (see that link above for more), and it's infuriating. Generic drugs are off patent, by definition, and they're supposed to be cheap. Taking advantage of regulatory loopholes and perverse incentives to jack their prices up is shameful, unproductive, and expensive.
[...] Marathon itself appears to be about to disappear. And why not? They've turned a quick buck. Endpts, who have been doing a great job on this story, couldn't find anyone who thought that the company had spent more than $70 million on the drug's approval, and it was probably a lot less. So $140 million, plus milestones and royalties, is a nice return. But there's more money coming than just that – the company got a priority review voucher from the FDA for bringing a rare pediatric disease drug to the market, and they can sell that on the open market. I'd guess that it could bring in another $100 million or so
The priority review voucher is an incentive program that provides companies, that get a drug approval for a neglected or rare disease, a voucher that entitles them to a more speedy review (under six months instead of ~10 months) for a future drug. This is a great program; however, Marathon Pharmaceuticals deliberately exploited this program by conducting a very small trial using a generic drug (another loophole).
Previous Story: https://soylentnews.org/article.pl?sid=17/02/11/2116252
A new and non-viral approach to CRISPR has been used to treat Duchenne muscular dystrophy in mice:
A new version of the CRISPR-Cas9 gene-editing technology called CRISPR-Gold has successfully restored the correct sequence of the dystrophin gene in a mouse model of Duchenne muscular dystrophy (DMD), a new study revealed.
Researchers found that an injection of CRISPR-Gold into DMD mice led to an 18-times-higher correction rate and a two-fold increase in a strength and agility test compared to control groups, according to a press release.
The study, "Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair," [DOI: 10.1038/s41551-017-0137-2] [DX] was published in the journal Nature Biomedical Engineering.
[...] Unfortunately, methods of delivering the components of this system, which include an RNA molecule called a guide RNA, a protein called the Cas9 nuclease, and the correct DNA sequence to replace the mutation (via donor DNA), have not been fully developed for human use. A primary technique used to deliver the components of this system relies on viruses, but this technique is plagued by complications and unwanted side effects.
In response, researchers at the University of California, Berkeley have developed a new approach called CRISPR-Gold, which used gold nanoparticles to deliver the components of this system in a mouse model of DMD. This method works by using gold nanoparticles to coat a modified DNA molecule that binds the donor DNA, which in turn is bound to Cas9 and the guide RNA.
This entire system is then coated by a polymer that will interact with a cell membrane and allow entry into a cell. Then, the components of the system are released into the cell as the coat breaks apart upon entry. The guide RNA, the Cas9 nuclease, and the donor DNA can then make their way into the nucleus and correct the mutation.
Also at TheScientist.
Previously: FDA Panel Recommends Rejection of Duchenne Muscular Dystrophy Treatment
Marathon Pharmaceuticals is Part of the Problem
Marathon Pharmaceuticals Cashes Out on Regulatory Loopholes
What is a Muscle Protein Doing in the Brain?
As the world knows, we face an emerging virus threat in the Wuhan coronavirus (2019-nCoV) outbreak. The problem is, right now there are several important things that we don't know about the situation. The mortality rate, the ease of human-human transmission, the rate of mutation of the virus (and how many strains we might be dealing with – all of these need more clarity. Unfortunately, we've already gone past the MERS outbreak in severity (which until now was the most recent new coronavirus to make the jump into humans). If we're fortunate, though, we'll still have something that will be worrisome, but not as bad as (say) the usual flu numbers (many people don't realize that influenza kills tens of thousands of people in the US each year). The worst case, though, is something like 1918, and we really, really don't need that.
[Ed note: The linked story is by Derek Lowe who writes a "commentary on drug discovery and the pharma industry". He is perhaps best known for his "Things I Won't Work With" blog entries which are as hilarious as they are... eye opening. I have found him to be a no-nonsense writer who "tells things as they are", holding no punches. The whole story is worth reading as he clearly explains what a coronavirus is, about the current one that reportedly originated in Wuhan, China, what could be done about it, how long that would likely take, and what can be done for those who have already been infected. --martyb]
Previous Stories Referencing Derek Lowe:
Machine Learning Comes to Biochemistry
Ignition! The Funniest, Most Accessible Book on Rocket Science is Being Reissued
Another Failed Alzheimer's Disease Therapy
Marathon Pharmaceuticals is Part of the Problem
Lobbying Results in FDA Approval for Controversial Drug
"Right to Try" New Experimental Medicine and the Value of Experts
Cancer Hazard vs. Risk - Glyphosate
A Terrific Paper on the Problems of Drug Discovery
Things I Won't Work With
(Score: 3, Informative) by migz on Sunday February 12 2017, @09:57AM
I cannot understand why companies are always painted as the culprits, when the problem is one that has been created by government. In this case the FDA should not be involved at all in regulating anything except fraud.
If company A invents a drug, then that is great. Some would argue that as a result of those costs, companies should be granted a monopoly to license that drug. I don't think that is a good idea. A large chunk of those costs are invented by the incumbent in conspiracy with the regulators to keep competition out. This is the modern equivalent of a guild system. Anybody should be allowed to produce anything in their basement, and the FDA should only be there to prevent fraud.
If someone sells chalk pills as aspirin, then they can get involved. They can even have a little FDA approved logo to show that they "have been tough". Heck if would probably be a good thing if there were private competitors to the FDA that had their own "safety marks". If I want to buy cut price acetylsalicylic acid from the cafe, nobody should stop me. If Beyer pharmaceutical's want's to put an Asprin(R) on theirs and charge more, then they should be allowed to. Nobody else should be allowed to as long as they control the trademark, since that would be fraud. The FDA should however leave everybody else alone.
(Score: 2, Informative) by Anonymous Coward on Sunday February 12 2017, @04:06PM
In this case the FDA should not be involved at all in regulating anything except fraud.
If someone sells chalk pills as aspirin, then they can get involved.
You are hopelessly naive. The FDA wasn't created out of nowhere. It exists because people were being killed. [wikipedia.org]
No amount of after the fact action can undo death or serious injury.
The FDA is imperfect because it is a creation of imperfect humans, but your 'solution' is a recipe for far worse results.
We've already been down that path.
(Score: 2) by migz on Sunday February 12 2017, @05:08PM
> You are hopelessly naive.
> The FDA wasn't created out of nowhere.
I never claimed that it was.
>It exists because people were being killed.
Yep, that's fraud.
> No amount of after the fact action can undo death or serious injury.
>The FDA is imperfect because it is a creation of imperfect humans,
>but your 'solution' is a recipe for far worse results.
Nope. You have not refuted a single word, nor have you presented anything in support of your contention.
> We've already been down that path.?
Really? There was a time that the FDA only acted as a vetting agency, and had competition? When was this?
(Score: 0) by Anonymous Coward on Sunday February 12 2017, @05:48PM
> Ad hominum
Nope. For your future reference:
Ad hominem: "You are wrong because you are stupid."
Not ad hominem: "You are stupid because you are wrong."
(Score: 1) by Roger Murdock on Monday February 13 2017, @12:43AM
>>It exists because people were being killed.
>Yep, that's fraud.
It's not fraud if the deaths were from compounds that were accurately listed.
> nor have you presented anything in support of your contention
Neither have you really, just a bunch of opinions and something about an FDA conspiracy. How is any research going to be funded if the final product will just be copied as soon as it hits the market? Or do you think R&D costs are actually so low (if it weren't for the FDA) that being (marginally) first to market would make up for it?
(Score: 2) by sjames on Sunday February 12 2017, @05:46PM
There is justification for regulating novel drugs and inactive ingredients in drugs, but fundamentally, the FDA is just as much after the fact as anyone else. They do not have anything in place that could actually prevent a bad actor from including a toxic substance into a remedy except the knowledge that the after-the-fact consequences would be ruinous.
It's fine that we have the FDA provide a means by which a novel substance can become approved for human consumption. But once it is, the FDA should butt out other than periodic checking that the drug contains what it says it does in the amount it claims (or perhaps the FTC should do that, they seem to manage it without quadrupling the price).
(Score: 0) by Anonymous Coward on Sunday February 12 2017, @04:12PM
Some would argue that as a result of those costs, companies should be granted a monopoly to license that drug. I don't think that is a good idea.
Do you have a better idea?
Doing research, developing drugs, and running clinical trials all cost money. That money has to come from somewhere and many people are not happy with tax money even paying for the first part.
(Score: 2) by migz on Sunday February 12 2017, @05:12PM
> Do you have a better idea?
Sure. Don't grant monopolies.
> Doing research, developing drugs, and running clinical trials all cost money.
Sure. None of those should be required to manufacture and distribute substances.
> That money has to come from somewhere
No it does not. You only need the money if the FDA forces you to do it. Otherwise people can find other ways to fund research, trials, and drugs.
> ... any people are not happy with tax money even paying for the first part.
I'm not happy with tax money paying for ANY part of this WHATSOEVER. The FDA should be self funding.
(Score: 0) by Anonymous Coward on Sunday February 12 2017, @10:43PM
Otherwise people can find other ways to fund research, trials, and drugs.
Without patent protection, how would pharmaceutical companies fund the research necessary to develop new drugs? Should they try to rely on trade secrets, enter into exclusive contracts with healthcare providers, or should they just stop making new drugs?
(Score: 2) by sjames on Sunday February 12 2017, @10:09PM
The FDA is a serious enabler but Marathon and their ilk play it for all it's worth. You may leave your backpack on the bench at the park, but I'm still a thief if I take it away, remove your ID, and treat it as my own.
(Score: 2) by Justin Case on Sunday February 12 2017, @11:39AM
This is not a case of too little regulation but too much.
The only thing the FDA should control is whether a product gets a sticker or logo saying "approved by FDA". Then, if you're the sort of person who wants to wait for the results of 10 years of tests, you don't try anything that might help you until 10 years have gone by and billions of dollars have been spent. However, if you don't have ten years, maybe you can risk an experiment. Or get something from Canada without making yourself a felon and risking spending those last six months of your deteriorating life in jail.
(Score: 3, Insightful) by Rosco P. Coltrane on Sunday February 12 2017, @11:52AM
And they're also allowing the likes of Marathon to make the rest of the drug industry look like greedy sociopaths
Because it isn't?
The whole pharma industry is an unending lithany of profiteering on the back of sick people, price fixing and corruption. When was the last time you saw any of these companies putting out a truly useful molecule at a reasonable price for the good of the people?
(Score: 2) by Justin Case on Sunday February 12 2017, @12:02PM
Since you don't need or want money, perhaps you could do the good deed you seem to expect others to do, and start a pharma company that is unprofitable. I mean, no one's stopping you.
No one but those pesky regulators, that is.
(Score: 3, Interesting) by Rosco P. Coltrane on Sunday February 12 2017, @12:09PM
Can't you understand the difference between a new, useful molecule at, say, 5x profit margin and an old, tired one at 100x?
I'm all for pharma companies making profit - especially considering how much R&D and red tape they have to deal - but I'm totally against obscene profits that benefit no-one. Most pharma companies don't do real R&D to solve real health problems anymore: they just do variants of old shit they can patent and profit on. Incidentally, part of the reason why they behave like that is the system the very regulators you seem to value so much set in place - the others being, they're greedy bastards.
(Score: 2) by Justin Case on Sunday February 12 2017, @12:47PM
Yes, I understand the difference, and since you do too, buy the rights to the old tired one and sell at 2x.
the very regulators you seem to value so much
Uh, no, that would be someone else. I'm strongly deregulate when it comes to the FDA. You should have a choice whether or not to buy and use FDA approved substances.
they're greedy bastards.
In other words, they're a group of people who want or need money. Since you don't want or need money (great to be you I guess) get off your high horse and do something good for the world instead of mumbling around your Cheetos about what others should do. Start an unprofitable pharma company. Round up investors who, like you, don't want or need money but just want to Do Good Things For The World. Promise your investors a negative rate of return as you spend all their money developing or buying your product line. Sell at a loss and go to sleep every night knowing you're not a bastard.
What are you waiting for?
(Score: 2) by sjames on Sunday February 12 2017, @05:17PM
You claim to know the difference, but you demonstrate that you don't.
If the FDA were stripped of the power to grant exclusivity in exchange for ass kissing and we then enforced existing laws against such practices as paying potential competitors to stay out of the market AND we force the FDA to treat generics as generic rather than treating them as a brand new product, we might actually see companies willing to produce generic drugs in exchange for a reasonable profit (that is, not at a loss but not for hundreds of times the cost).
(Score: 0) by Anonymous Coward on Sunday February 12 2017, @02:22PM
Step 1: allow imports from other reasonable countries.
Step 2: give the FDA the ability to call out sham differences where two drugs are different enough to get different rules but essentially the same
Step 3: perhaps include price versus benefit into the mix of things considered during patent and drug approval proceedings
Step 4: tell Marathon that under the new rules, their 'invention' does not add to the availability of treatments and so no longer qualifies for a monopoly
Step 5: (For extra credit) consider penalties for those gaming the system
If you believe in a fundamental right to medical care, the pharma is not just another industry.
It, and the medical profession in general, have a responsibility to help folks.
This doesn't mean they can't make a good living.
Just not a crazy one with contrived scarcity, non-productive efforts, and a general attitude of anything for a buck.
These special rules are there to support bringing new treatment options where it helps the patient.
They are not there to cause windfall profits.