Experience of Patisiran With Transthyretin Stabilizers in Patients With Hereditary transthyretin-mediated Amyloidosis

Abstract

Aim: Examine safety and pharmacodynamics of patisiran alone or with concomitant transthyretin stabilizers from the Phase II open-label extension study and safety and efficacy of patisiran in patients with prior transthyretin stabilizer use from the Phase III APOLLO study. Patients & methods: Post hoc analyses in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Results: Patisiran safety was consistent regardless of concomitant or prior transthyretin stabilizers. In the Phase II open-label extension (n = 27), transthyretin reduction was similar over 24 months, regardless of concomitant transthyretin stabilizers. In APOLLO (n = 225), patisiran-treated groups showed stabilization or improvements in neurological function (modified Neuropathy Impairment Score +7) and quality of life (Norfolk Quality of Life-Diabetic Neuropathy questionnaire) at 18 months, regardless of prior transthyretin stabilizers. Conclusion: Patients benefit from patisiran regardless of transthyretin stabilizer use.

The current landscape of nucleic acid therapeutics

“…This suggested patisiran can halt and reverse disease progression 82 . More recently, post hoc analyses of data from the phase 2 open-label extension and the phase 3 trial suggested that patients benefit from patisiran even when simultaneously receiving oral small-molecule TTR stabilizers (tafamidis or diflunisal) 83 .…”

Diagnosis and treatment of hereditary transthyretin amyloidosis with polyneuropathy in the United States: Recommendations from a panel of experts

“…Although the different treatment modalities may be complementary, there is limited evidence for the role of combination therapy. A post hoc analysis showed that patisiran efficacy and safety were similar with or without concomitant TTR stabilizer use, although this combination has not been explored further in clinical studies 88,89 . Similarly, other combinations of approved therapies (with, e.g., doxycycline, tauroursodeoxycholic acid, green tea, and other therapies) have yet to undergo rigorous clinical testing.…”

Practical Guidance for the Use of Patisiran in the Management of Polyneuropathy in Hereditary Transthyretin-Mediated Amyloidosis

“…A post-hoc analysis of the phase II OLE and phase III trials compared patisiran alone and with concomitant use of a TTR stabilizer, either tafamidis or diflunisal. 37 During the phase II OLE, 26% of patients received patisiran alone, 48% of patients received tafamidis with patisiran, and 26% of patients received diflunisal with patisiran. Patients in the phase III APOLLO trial were on patisiran alone, but 33% had previously used tafamidis and 20% had previously used diflunisal.…”