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What's going on with gene therapies?

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Re: What's going on with gene therapies?

#11

Post by condiment »

To summarize, the problem with gene therapy is simply that it's extremely expensive and the list of qualified clients is extremely small. That's because these therapies have been necessarily targeted towards ultra-rare and assuredly fatal diseases.

That approach developed the technologies, but what if a mass market approach is what is required to create the economies of scale we need to actually benefit from this science long-term? Consider a cure for the common cold. All of the technology exists. We can take a tissue or fluid sample and extract viral genomes, comparing against a database of over 100k viruses. We can develop MRNA vaccines that target specific viral proteins. We can do both of these things using current technology in a timeframe of less than a day.

To me this is the next great leap. Gene therapy is less a technology problem than it is an infrastructure problem, and rare diseases cannot support the infrastructure. But there are plenty of wealthy people who would pay $10k, maybe even $50k, out of pocket to cancel a cold. Rare diseases bootstrapped the tech, common diseases can scale it, and once scaled, everyone benefits.

Re: What's going on with gene therapies?

#12

Post by pedro_caetano »

From what I understand the situation is quite the opposite, there is a huge pipeline of investment both in startups as well as very large corps on the development and application of gene therapy.

As anecdata, Luxturna costs north of a quarter of a million per vial, it treats a fairly rare disease (Leber congenital amaurosis). Roche still poured millions into development.

Bio-tech, specially in a Medical field, is a very difficult business. The strategy for must startups is to get bought by a very large pharma company. The issue is that these companies often run out of runway, specially when dealing with later pre-clinical, clinical, and regulatory costs.

Re: What's going on with gene therapies?

#13

Post by VirusNewbie »

condiment wrote: post #11

To summarize, the problem with gene therapy is simply that it's extremely expensive and the list of qualified clients is extremely small. That's because these therapies have been necessarily targeted towards ultra-rare and assuredly fatal diseases. That approach developed the technologies, but what if a mass market approach is what is required to create the economies of scale we need to actually benefit from this sci…

Well, rare disease certainly gets people to pilot the tech. I'm certainly not going to try some ultra-experimental gene therapy to be immune to the common cold or fix my allergies, I don't know what the side effects might be.

But if I was staring down some awful rare disease, then sure, let's roll the dice.

Re: What's going on with gene therapies?

#14

Post by itake »

southernplaces7 wrote: post #10
itake wrote: post #9

Earlier quoted context omitted.

I think they are angry because a solution is available but not accessible. People are gatekeeping resources that would enable access to treatment because for big companies, spending $1 to earn $1 isn’t a sustainable business model.

My understanding of the comment wasn't that. It was that a solution for his adult version hasn't yet been developed because it's not commercially viable to do so due to its rarity. This of course brings me right back to the points I made in my own comment above. Resources are scarce, and commercial viability, or at least resource viability for all the effort of development, is a factor under any system you choose to…

I think we are saying the same thing. Companies chase high risk high reward over low risk low reward.

Presumably, curing a genetic disorder for a very small number of people using existing technology is low risk and low reward.

> Why wouldn't it be sold if it were available?

Just because something works in a small lab doesn’t mean it’s ready to sell. To launch a product, companies need to do a lot more: testing, certifications, licenses, marketing, training, and more. Sometimes, even when a product is finished, companies decide not to launch it if their budget or priorities shift elsewhere.

A related example could be unreleased movies like Batgirl Or Coyote vs. Acme. The films were completed, but they felt their marketing dollars would be better spent on other projects.

Re: What's going on with gene therapies?

#15

Post by rubidium »

colechristensen wrote: post #5
JohnMakin wrote: post #2

I have an extremely rare autosomal dominant subtype of a certain genetic disorder that affects maybe less than a few thousand individuals at any one time in the USA. Much common versions of the disorder that affect children have been successfully treated/cured with gene therapy. However gene treatment unlikely to ever reach people like me because so few are affected by it, it's not viable commercially. It's extremely…

One of the sort of strange things about gene therapy is how cheap a custom solution really is. You can arbitrarily genetically modify a plant or bacteria for a few hundred dollars to the level of arbitrarily picking the letters of a gene sequence (or you know, doing some research and doing something real) and getting the gene modifying tools manufactured very very cheaply. If you have a slightly different form of a m…

You’ve taken a very small slice of the total workflow to develop cas9 crispr edits. Yes some components are “not crazy expensive”, but that’s not therapeutic production levels. And no sequencing. And no bioinformatics. And then zero tissue targeting/ delivery or safety studies.

So $5k is a massive stretch. I do think costs are coming down. But don’t want to oversell current state of “garage hacking” either.

Re: What's going on with gene therapies?

#16

Post by searine »

condiment wrote: post #11

To summarize, the problem with gene therapy is simply that it's extremely expensive and the list of qualified clients is extremely small. That's because these therapies have been necessarily targeted towards ultra-rare and assuredly fatal diseases. That approach developed the technologies, but what if a mass market approach is what is required to create the economies of scale we need to actually benefit from this sci…

The issue isn't a technical one with gene-therapy. The issue is ethical.

Editing your DNA can be dangerous or even deadly if it doesn't work. Modern methods have mostly solved this, but there is still a lot of hesitancy due to prior failures/tragic deaths.

It is also ethically foggy. Somatic edits, edits that will die with you and do not change your sperm or eggs, are one thing, but when you start making germline changes, that impacts everyone who may inherit your genes. You may consent to a germline change, but will your children? Or your children's children's children? You may have the money now to make they change, but will they have the money to change it back?

Small genetic changes also have a complex spectrum of phenotype outcomes. If you start making germline changes that are not found in nature or are under-studied, that can have compounding unintended consequences. For example, if you spec into a dozen intelligence SNPs, that may also increase your risk for a pandora's box of mental illnesses.

So no, economies of scale will not solve this. It would be a disaster.

Re: What's going on with gene therapies?

#17

Post by [deleted] »

searine wrote: post #16
condiment wrote: post #11

To summarize, the problem with gene therapy is simply that it's extremely expensive and the list of qualified clients is extremely small. That's because these therapies have been necessarily targeted towards ultra-rare and assuredly fatal diseases. That approach developed the technologies, but what if a mass market approach is what is required to create the economies of scale we need to actually benefit from this sci…

The issue isn't a technical one with gene-therapy. The issue is ethical. Editing your DNA can be dangerous or even deadly if it doesn't work. Modern methods have mostly solved this, but there is still a lot of hesitancy due to prior failures/tragic deaths. It is also ethically foggy. Somatic edits, edits that will die with you and do not change your sperm or eggs, are one thing, but when you start making germline cha…

[deleted]

Re: What's going on with gene therapies?

#18

Post by condiment »

searine wrote: post #16
condiment wrote: post #11

To summarize, the problem with gene therapy is simply that it's extremely expensive and the list of qualified clients is extremely small. That's because these therapies have been necessarily targeted towards ultra-rare and assuredly fatal diseases. That approach developed the technologies, but what if a mass market approach is what is required to create the economies of scale we need to actually benefit from this sci…

The issue isn't a technical one with gene-therapy. The issue is ethical. Editing your DNA can be dangerous or even deadly if it doesn't work. Modern methods have mostly solved this, but there is still a lot of hesitancy due to prior failures/tragic deaths. It is also ethically foggy. Somatic edits, edits that will die with you and do not change your sperm or eggs, are one thing, but when you start making germline cha…

You're conflating gene therapies vs. the human genome with gene therapies vs. viral genomes. In some cases, the illnesses are genetic, but this article is specifically about how gene therapy companies keep going out of business trying to cure rare genetic illnesses! Even if the technology is the same, the uses are very different and regulatory approval is still required for the application of the technology.

That's not to say there aren't additional ethical challenges that would arise if gene therapies were cheap, but the ethics concerns you're raising seem like future concerns, relevant to a world that does not yet exist.

Re: What's going on with gene therapies?

#19

Post by mandevil »

condiment wrote: post #11

To summarize, the problem with gene therapy is simply that it's extremely expensive and the list of qualified clients is extremely small. That's because these therapies have been necessarily targeted towards ultra-rare and assuredly fatal diseases. That approach developed the technologies, but what if a mass market approach is what is required to create the economies of scale we need to actually benefit from this sci…

This is actually a lot harder than you think because we still don't understand gene therapy well enough to be able to be sure that any given treatment works without the really expensive part, the Randomized Control Trial. In 2017 a gene therapy was approved in the US for RPE65-associated Retinitis Pigmentosa, Luxterna, the first in-vivo gene therapy approved by the FDA (yay! List price was a mere 425,000/eye). Just a few months ago J&J announced that their gene therapy targeting a different gene, RPGR, missed its primary end-point, only 22 out of 55 treated patients showed improvements on at least two of the measures in the LUMEOS trial and there was no statistically significant improvement on their primary measure. That result happened even though this was mostly just "take the thing that already worked for Luxterna, and do a different gene." The problem is that the human body is far more complicated than computers, and does not scale the same way.

This is why regulators are very wary of "Right to Try" type stuff, they want to be sure that medical treatments are actually effective before they are available to the broad public. These sorts of RCTs are still quite necessary, and they are the really expensive thing in drug discovery. (Well, it's both that they are expensive to run and also they kill all sorts of drugs that don't actually work.)

Re: What's going on with gene therapies?

#20

Post by toast0 »

itake wrote: post #14
southernplaces7 wrote: post #10

Earlier quoted context omitted.

My understanding of the comment wasn't that. It was that a solution for his adult version hasn't yet been developed because it's not commercially viable to do so due to its rarity. This of course brings me right back to the points I made in my own comment above. Resources are scarce, and commercial viability, or at least resource viability for all the effort of development, is a factor under any system you choose to…

I think we are saying the same thing. Companies chase high risk high reward over low risk low reward. Presumably, curing a genetic disorder for a very small number of people using existing technology is low risk and low reward. > Why wouldn't it be sold if it were available? Just because something works in a small lab doesn’t mean it’s ready to sell. To launch a product, companies need to do a lot more: testing, cert…

> Presumably, curing a genetic disorder for a very small number of people using existing technology is low risk and low reward.

I don't know if that presumption is reasonable. Yes, low reward; but I suspect the risk/cost for a gene therapy is about the same, regardless of the number of people affected. You still need to do all the pre-human trials, which are still expensive; then you've got to do human trials, which are still expensive ... and if there aren't enough potential patients, you might not even be able to run a reasonable trial. (although the article describes a situation of a single patient treatment, you obviously can't run a human trial of that). IMHO, that makes it higher risk than targeting something that affects many more people.

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