[jorlow]

The article says "patients must undergo a preparatory treatment with a chemotherapy drug to remove any native stem cells that might remain in their bone marrow." It doesn't make much difference to the patient if it's the Lyfgenia itself or the chemo drug, if the chemo drug is a requirement. Right?

[skissane]

There is active research on doing gene therapy without requiring chemotherapy (or radiation) first. It has been shown to work in mice, and they may eventually get it working in humans too. It would likely require a significant modification to these gene therapies though, since one approach is to alter the method of growing the stem cells to produce a significantly higher number, and then transplant that, with the hope that the transplanted edited cells outnumber and outnumber the original unedited ones. So very likely the FDA would treat that as a new therapy requiring a new approval process.

https://med.stanford.edu/news/all-news/2019/05/radiation-fre...

There is also ongoing research into immunotherapy for killing stem cells, as an alternative to the existing methods of chemotherapy and radiation. Potentially, immunotherapy could have significantly reduced secondary cancer risk.

https://jhoonline.biomedcentral.com/articles/10.1186/s13045-...

[confused_boner]

I was thinking more that it could poison the reputation of gene therapy by causing folks to falsely associate cancer with gene therapy. And that false stigma could carry on even if one day chemo was no longer needed.

[eszed]

Fair enough, but there remains the possibility of finding an alternate, safer chemotherapy drug.

Does anyone know if changing the drug would require a new FDA approval for the entire regimen, or could the protocol be easily changed?

[firejake308]

It's reasonable to expect small improvements in the risk profile, but I think blood cancer is going to be a side effect for any drug following this basic idea. You will always need some chemo to destroy the defective blood-making stem cells before replacing them with the genetically-modified blood-making stem cells, and any chemo that is strong enough to kill all of the blood-making stem cells in your body is necessarily going to have a risk of damaging healthy cells and turning them into pre-cancer cells. So the risk can be reduced but probably not eliminated.

[skissane]

> Does anyone know if changing the drug would require a new FDA approval for the entire regimen, or could the protocol be easily changed?

The FDA-approved prescribing information will recommend a particular chemotherapy regimen, but clinicians will be free to substitute alternatives if they believe those are clinically superior. They won't need permission from the FDA or the manufacturer to do that; clinicians deviate from the FDA-approved manufacturer recommendations all the time ("off-label prescribing").

If the manufacturer wants to update the official recommendations in the prescribing information, then they'll need FDA approval for that. But it is possible for clinicians to publish their own treatment guidelines (e.g. in medical journal articles), independent of the manufacturer, and the FDA has no control over those.