$ions and $alny: addressing #amyloidosis piece:
"Drug specific TTR-Rx (partner GSK):
a. Watch issue: Once both IONS and ALNY TTR polyneuropathy results come out the IONS results are meaningfully worse from an efficacy standpoint
b. IONS thrombo data in TTR Poly is bad enough that it more than offsets the much more cumbersome and toxic ALNY infusion system. "
I think there is a reasonable chance that neither $alny or $ions drug works for TTR. Neither of the drugs are addressing the amyloid that is already in these patients, which is likely causing the toxicity. They are halting or slowing production of new amyloid. 1) it may be too late just to cut off new production, or a longer trial may be needed for that to be meaningful. For polyneuropathy, if amyloid is already coating the nerves, what will these drugs do?
The other issue: TTR is a normal protein in the body. In the case of amyloidosis, the tetramer breaks apart and the components misfold into amyloid. However, both of these drugs stop production of TTR, not just abnormal TTR. What is the off target effect of targeting TTR, which is a useful protein in the body.?
THe other issue. GSK has cancelled the $ions cardiomyopathy specific studies and $alny drug caused increased mortality. So we know something in not right in the cardio TTR space.
THese drugs may work and i hope they do, but there are plenty of reasons to doubt.
AI
