[ethbro]

> is of questionable effectiveness --- it improves quality-of-life metrics but not necessarily clinical ones like blood fat levels

"Although based on a small number of patients and episodes, overall pancreatitis incidence up to 2 years post-alipogene tivarvovec injection decreased by 5-fold"

"However, several signs of clinical efficacy independent of plasma TG were noticed up to 2 years after LPL gene transfection and raised the possibility that TG-rich lipoprotein characteristics, particularly the size, lipid content and kinetics of CMs, rather than plasma TG concentration per se, are the best surrogate markers of pancreatitis risk in LPLD."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956470/#!po=37...

From what I read, 2-year follow-ups seem to find continued (post-26 week) activity of the inserted gene.

So it's inaccurate to say there were no clinical improvements.

[tptacek]

I worried about the word "clinical" here, which might not be what I meant. It is not, however, inaccurate to say that concerns about efficacy were behind EU health system refusal to pay, and behind the therapy being taken off the market.

[ethbro]

True. The question seems to be correlating the long-term decrease in serious episodes and gene expression (observed, albeit in a low sample size) with a marker (plasma TG did not change, but centrifuged TG composition by weight did).

The injustice here, if it exists, seems to be that the system is poorly configured to treat rare diseases.

Afaik, the FDA (regulatory side, for non-US readers) began granting more permissive experimental waivers for this sort of thing.

But the insurance side seems well within their rights to not pay by saying "This treatment has not been demonstrated effective to our standards." Something which is likely impossible given the cost of running normal trials and target population (small).

Hopefully, in the future, this will be addressed as more gene therapies become available and individualized medicine becomes the norm (similar to the revolution oncology has gone through in the past 30 years).