Safety of new drugs for hATTR

Inotersen and patisiran decrease total transthyretin (TTR) production (mutant and non-mutant), which leads to lower levels of all TTR. In hereditary transthyretin amyloidosis (hATTR) clinical trials, treatment with both drugs has decreased neuropathy impairment and improved quality of life measurements. 
​
Patients receiving patisiran are pretreated with dexamethasone, oral acetaminophen, ranitidine or famotidine and diphenhydramine to reduce infusion-related reactions. Patients receiving patisiran should be monitored for infusion reactions and peripheral edema.
 
Patients receiving inotersen must be monitored for thrombocytopenia and changes in renal function. This would require careful titration and monitoring in patients with renal or cardiac disease.
 
These drugs act on TTR and not on correcting the mutation that causes the abnormal TTR to be produced.  TTR is a protein found in serum and cerebrospinal fluid, where it transfers thyroxine and retinol. The long-term effect of TTR elimination is unknown.
 
Because the alternate is liver transplantation, patisiran and inotersen will likely be the preferred treatment until a genome edit is created to correct the abnormal protein mutation.