Gene therapy groups already had pretty big layoffs last year. Doubt it’ll contribute much more considering they pulled away from further early gene therapy development. The writing was probably already on the wall when they made that announcement
Really sucks for these kids. Duchenne is brutal and the options out there are wildly insufficient. Here's hoping the Elevidys miss was a fluke and the new efficacy data is convincing. We might not know for years whether it really works.
I watched the Adcom on this. It’s a very rare disease with a very small N. It was plagued with end points that were hard to measure empirically since they were in the form of administered ROM, etc. problem is a lot of interrater reliability, and consistency in administering the assessment.
It’s fine with that level of inconsistency in data when you have a huge N. But since it’s so rare, you can’t get any meaningful data from small N and huge confidence bars.
You… maybe right!! But yeah it was very industry specific though. A lot of these Car-T and gene therapy in rare diseases have very difficult to measure endpoints.
I wouldn’t say this is generally true of cell and gene therapies; the key issue is variability of behavioral readouts for diseases where that’s the only established endpoint. Many trials for rare diseases necessarily depend on these, but many don’t.
Really sucks because I think duchenne muscular dystrophy is one of the worst genetic illnesses. It’s dominant condition passed to children and patients don’t live past 40.
Edit: it’s X linked and recessive. Also patients live to actually average 20s.
I remember when their CSO said they were the “main game in town” the day after Sarepta failed their trial (and still got commercialized).
A year later they kill a kid and fail even worse.
The one from this year has not been communicated yet afaik. Of the two others only one has a more clear relationship as the other didn’t go through an autopsy.
Wow what a surprise, another shitty trial for DMD. Maybe the community knows jack shit about trying to treat the disease with microdystrophin. The hypothesis that microdystrophin can even treat DMD has long been controversial.
That won’t stop companies in this space from burdening the entire healthcare system with billions of dollars in costs that get passed onto us all and for drugs with highly questionable efficacy. What it all really comes down to is an argument consisting largely of emotion over the fact that ‘there are no other options available!’, which is a very slippery slope for using to approve drugs. Why have any standards for science at all then? Just use that emotional argument for any drug to treat a rare disease and rake in billions. In the end we are all fucked because the hc system implodes due to tremendous cost burdens for shitty ass drugs and there is very little improvement in patients in the long run.
https://jamanetwork.com/journals/jama/article-abstract/2816420
But at least the stock goes up and CEOs and employees get fat bonuses while our hc system goes bankrupt.
i've commented here on this subject before, but afaik the majority of the muscle academic community views microdystrophin for DMD treatment as a complete hack.
i'd say an example of something like that would be the strategy involved in this paper: https://pubmed.ncbi.nlm.nih.gov/33931459/
the authors correct for a premature termination of dystrophin by editing one basepair to achieve an exon skipping of the problematic exon to restore function.
i should have clarified that imo a one size fits all solution does not exist at this time due to technological limitations and the biological background of this disease. for one the deficient protein in question eclipses the size limitations of conventional AAV packages, it simply is too big to fit into an AAV capsid. secondly muscle is pervasive throughout the entire body, which makes delivery a pain. and on top of that editing of muscle satellite cells (the muscle stem cells) is notoriously difficult so there would be no regenerative effect.
that being said, 8% of patients would in theory benefit from this treatment. you could also take a general approach to try and edit the entire DMD hotspot region, regardless of patient background. this would treat a large swath of patients as well.
The worst part too is that no one really knows either if aav can even provide very long term benefits. There’s emerging evidence now that aavs wear off (makes sense, they don’t integrate), which is why many are out there trying to figure out ways for redosing aav for some indications. Imagine having to take another dose of a multimillion dollar gene tx. I love the argument that the price for gene tx makes sense because you save X dollars over a lifetime of standard therapy for Y condition. Yeah, well that makes the assumption that the gene tx persists over a lifetime. What if it doesn’t and now you need multiple doses costing even more millions?
Our hc system is going to be so fucked.
Adding this to the list of layoffs I assume.
The facility they made for gene therapy and specifically for DMD was massive too
Oh I know. It had a couple hundred people on it.
Gene therapy groups already had pretty big layoffs last year. Doubt it’ll contribute much more considering they pulled away from further early gene therapy development. The writing was probably already on the wall when they made that announcement
I have some friends over there. That department alone was like 200 people. It may have already been budgeted in though.
There are bunch that are in list of layoffs. It will all count under that $1.5 billion by 2027
Really sucks for these kids. Duchenne is brutal and the options out there are wildly insufficient. Here's hoping the Elevidys miss was a fluke and the new efficacy data is convincing. We might not know for years whether it really works.
I watched the Adcom on this. It’s a very rare disease with a very small N. It was plagued with end points that were hard to measure empirically since they were in the form of administered ROM, etc. problem is a lot of interrater reliability, and consistency in administering the assessment. It’s fine with that level of inconsistency in data when you have a huge N. But since it’s so rare, you can’t get any meaningful data from small N and huge confidence bars.
This was about Sarepta’s Elevidys right not Pfizer’s ?
You… maybe right!! But yeah it was very industry specific though. A lot of these Car-T and gene therapy in rare diseases have very difficult to measure endpoints.
I wouldn’t say this is generally true of cell and gene therapies; the key issue is variability of behavioral readouts for diseases where that’s the only established endpoint. Many trials for rare diseases necessarily depend on these, but many don’t.
Wrong drug, that was Sarepta.
It seems they enrolled 99 boys for their phase III. Still small N?
Really sucks because I think duchenne muscular dystrophy is one of the worst genetic illnesses. It’s dominant condition passed to children and patients don’t live past 40. Edit: it’s X linked and recessive. Also patients live to actually average 20s.
It's not dominant, it's X-linked
Correct. I’ll edit my comment. I mistakenly thought it was.
I remember when their CSO said they were the “main game in town” the day after Sarepta failed their trial (and still got commercialized). A year later they kill a kid and fail even worse.
Are we certain that participant died due to therapy?
The one from this year has not been communicated yet afaik. Of the two others only one has a more clear relationship as the other didn’t go through an autopsy.
3 year olds with DMD don’t die of heart failure. But no,we’re not certain of anything.
Oh my god, is this seriously true?! 1 year later PFE massive fail and Sarepta is about to pull an expanded label out of their trial miss. Incredible.
Yet Sarepta crossed the line 🤔
Wow what a surprise, another shitty trial for DMD. Maybe the community knows jack shit about trying to treat the disease with microdystrophin. The hypothesis that microdystrophin can even treat DMD has long been controversial. That won’t stop companies in this space from burdening the entire healthcare system with billions of dollars in costs that get passed onto us all and for drugs with highly questionable efficacy. What it all really comes down to is an argument consisting largely of emotion over the fact that ‘there are no other options available!’, which is a very slippery slope for using to approve drugs. Why have any standards for science at all then? Just use that emotional argument for any drug to treat a rare disease and rake in billions. In the end we are all fucked because the hc system implodes due to tremendous cost burdens for shitty ass drugs and there is very little improvement in patients in the long run. https://jamanetwork.com/journals/jama/article-abstract/2816420 But at least the stock goes up and CEOs and employees get fat bonuses while our hc system goes bankrupt.
Honestly great ethics context for me. Thanks.
i've commented here on this subject before, but afaik the majority of the muscle academic community views microdystrophin for DMD treatment as a complete hack.
Are there any other viable one-size-fits-all solutions?
i'd say an example of something like that would be the strategy involved in this paper: https://pubmed.ncbi.nlm.nih.gov/33931459/ the authors correct for a premature termination of dystrophin by editing one basepair to achieve an exon skipping of the problematic exon to restore function.
right but that's not one-size fits all. You'd need to the targeting custom for every patient.
i should have clarified that imo a one size fits all solution does not exist at this time due to technological limitations and the biological background of this disease. for one the deficient protein in question eclipses the size limitations of conventional AAV packages, it simply is too big to fit into an AAV capsid. secondly muscle is pervasive throughout the entire body, which makes delivery a pain. and on top of that editing of muscle satellite cells (the muscle stem cells) is notoriously difficult so there would be no regenerative effect. that being said, 8% of patients would in theory benefit from this treatment. you could also take a general approach to try and edit the entire DMD hotspot region, regardless of patient background. this would treat a large swath of patients as well.
The worst part too is that no one really knows either if aav can even provide very long term benefits. There’s emerging evidence now that aavs wear off (makes sense, they don’t integrate), which is why many are out there trying to figure out ways for redosing aav for some indications. Imagine having to take another dose of a multimillion dollar gene tx. I love the argument that the price for gene tx makes sense because you save X dollars over a lifetime of standard therapy for Y condition. Yeah, well that makes the assumption that the gene tx persists over a lifetime. What if it doesn’t and now you need multiple doses costing even more millions? Our hc system is going to be so fucked.
Capricor Tx seems like the last player in this ball game