Gene therapies are coming, but I’m not sure who will be able to afford them any time soon:
New gene therapy, to be priced at $4.25 million, has already transformed children’s lives
A new gene therapy for an ultra-rare disease will have a wholesale cost of $4.25 million, making it the world’s most expensive drug.
The one-time treatment, Lenmeldy, won US regulatory approval on Monday to correct the underlying cause of a hereditary condition called early-onset metachromatic leukodystrophy, or MLD.
MLD is a fatal disease in which infants sometimes start to lose the ability to walk and talk. Orchard Therapeutics said the drug’s price “reflects its clinical, economic and societal value” in a statement Wednesday.
I will throw out a guestimate, but nobody really knows. I would say:
5 to 10 years for RCTs for consenting/willing adults (for age-related therapies) - you could argue that MiniCircle is alreadying doing this in Roatan.
10 to 20 years, but perhaps more likely 30 years for the reasonable cost aspect (but again, MiniCircle is doing their preliminary non-permanent “gene therapy” for $30,000 or so, so we’ll see.
The issue is that there are so many uncertainties.
About 20 years ago the gene therapy startup scene was hot in the SF Bay Area, companies like Avgenics and many others were getting tons of funding and everyone though the future was bright and happening quickly.
I had friends in the gene therapy business here in the SF Bay Area 20 years ago when a FDA-approved gene therapy trial that was taking place went horribly wrong. A young 19 year old man who was participating in the trial died when his body responded very negatively to the viral vector they were using. His death hit all the major newspapers in the USA at the time, front page. It killed the entire industry virtually immediately. All the funding went away, and all the startups died in pretty short order. And the venture money would not look at the field for a long time… like 15 years went by before they would start investing again.
We have some gene therapy biologists here in our forums so perhaps they can comment.
But I think that most of these gene therapy companies today are still using viral vectors (the shell of a virus that can integrate into our DNA) to get the gene segments integrated, but there are still many problems with this as these are random integrations. Since you don’t know where the newly inserted gene is going, it could disrupt an existing well-functioning gene. I don’t know how well the work is going for targeted gene therapies, so that you can specifically insert the new gene segment into a targeted spot of the genome. perhaps someone else here has current knowledge in this area.
You also have random political factors that can hugely impact the work of biotech startups; when George Bush was elected president he shut down all the embryonic stem cell research in the country virtually overnight. Could a similar situation happen with gene therapy if it seemed to be politically convenient? Its certainly possible.
While a lot of good progress is being made in gene therapy now, it seems to me there are still significant hurdles to overcome to make it more broadly available and less expensive. I believe some of the hurdles are things like doing targeted delivery of the genes (vs. random), optimal delivery techniques to maximize transfection rates/ integration in the right areas of the body to be effective, and navigating the intellectual property landscape to get access to the different technologies a given company may need to use to delivery the therapy.
Given the high prevalence of the diseases mentioned (targeted) the price does not reflect the cost to develop the drugs or the production thereof. It does reflect the enormous greed of the drug companies and/or scientists involved. IMMORAL.
IMHO they are prepared to let tens or hundreds of millions of people die.
Is there anyone here who knows about gene therapy? As mentioned above, the price of follistatin gene therapy from Minicircle is $25k. But I was thinking that it might be possible to order the production of the corresponding plasmid vector from companies that specialize in such services (Human follistatin (Gene ID: 10468) Vectors - Regular Plasmid, Lentivirus & AAV I VectorBuilder). In this case, it is possible to order a drug that is as similar as possible to what Minicircle does, at least judging from the open information - that is, to create a plasmid vector with such parameters:
Vector type: plasmid (non-viral)
Promoter: EF1A or CMV
Marker: No marker (No marker)
Format: DNA plasmid
Regulatory System: Tet-Off: Gene expression is inhibited in the presence of doxycycline
Gene of Interest: Follistatin
It seems that the price of the drug will be well under $1000.
I am far from all this and do not understand what pitfalls this approach may have. And how will it be possible to verify that the obtained substance is really a plasmid vector of Follistatin?
I certainly understand the risks of this approach and it is more of a thought experiment at this stage of development of such services. I have an assumption that the same Minicircle do not synthesize the drug themselves, but order its synthesis from similar laboratories.
I’ve worked for a year with biologists out of Stanford U. on a gene therapy company, on a different type of non-viral, plasmid based vector. If you’re not a trained biologist I really doubt that you’d be successful. I’ve not dug deeply into the Minicircle approach, but from the sounds of it, its not like people are getting amazing results that you couldn’t just get from working out. These vectors are not permanently integrating and expressing in the genome. They are a short-term boost, at best, while they are in the bloodstream. Its interesting but hardly revolutionary or of significant benefit for people.
This isn’t a drug in the traditional sense of the word, its a biologic. The amount needed for an animal trial (eg. mouse or rat) which I would guess is what these companies are supplying this for, is going to be vastly different than the amount needed for a human implementation; so factor that in also. And, how much do you trust this lab producing this product?
Given the risk, and low benefits, I wouldn’t waste my time.
If you’re serious about it, team up with a biologist who has experience in using these types of vectors and has done animal testing.
I think mRNA should become more plug and play in the next few years, for mid-sized peptides. As you say, a short term boost, but capable of doing more than small molecule drugs, and more quickly and cheaply. IMO the big barrier is lack of knowledge as to what to make, not the ability to make it.
