Interim analysis shows sustained benefit of RNAi targeting TTR in ATTR cardiac amyloidosis

Patisiran treatment for ATTR cardiac amyloidosis: 18- month results of the phase 3 APOLLO-B study

News - May 22, 2023

Presented at ESC Heart Failure 2023 by Marianna Fontana, MD, PhD (London, UK)

Introduction and methods

Transthyretin (ATTR) amyloidosis is a progressive, fatal disease caused by transthyretin (TTR) amyloid accumulation in multiple organs, including the heart. In the heart, the deposition of TTR amyloid can lead to cardiomyopathy, which leads to worsening HF and arrhythmias, and decrease in functional status and QoL.

The RNAi therapeutic patisiran has been approved for treatment of ATTRv (variant) amyloidosis with polyneuropathy. Recently, results of the APOLLO-B phase 3 study showed that at 12 months, use of patisiran resulted in preserved functional capacity, health status and QoL in patients with ATTR cardiac amyloidosis, whereas patients on placebo had steady worsening of outcomes.

In the APOLLO-B study, 360 patients with wild-type or any TTR variant ATTR cardiac amyloidosis were enrolled. They had confirmed cardiomyopathy and a medical history of symptomatic HF. They were randomized 1:1 to patisiran 0.3 mg/kg IV Q3W or placebo. Patients who completed the 12-month period were invited to the open-label extension (OLE) study, in which all patients (n=334) received patisiran (0.3 mg/kg IV Q3W). Here, 18-month results of the OLE study were presented.

Endpoints were change from baseline of the APOLLO-B double-blind period till 18 months for functional capacity (assessed as 6-MWT), health status and quality of life by KCCQ-OS, cardiac biomarkers (NT-proBNP, troponin I), a composite endpoint of all-cause mortality, all-cause hospitalization and urgent HF visits, and all-cause death as a single outcome.

Main results

  • In patients receiving patisiran in both the double-blind and OLE periods, preservation of functional capacity (mean change in 6-MWT distance in m: -9.2 [SEM 6.0]) and health status and QoL was observed (mean change in KCCQ-OS: 0.2 [1.5], while in patients receiving placebo in the double-blind period and initiation of patisiran in the OLE period, slower rate of worsening of functional capacity (mean change in 6-MWT distance in m: -31.1 [5.5] and relative stability of healthy status and QoL (mean change in KCCQ-OS: -4.0 [1.5] was seen.
  • Similar trends were observed for cardiac biomarkers: NT-proBNP and troponin I levels were relatively maintained in patients originally randomized to patisiran, whereas patients originally randomized to placebo showed slower rise or stabilization of NT-proBNP and troponin I at 18 months.
  • No statistically significant findings were observed for the clinical composite outcome nor for all-cause death (as the study was not long enough and not powered for differences in death and hospitalization), but favorable trends with patisiran were seen from 9 months after patisiran use.
  • The safety profile of patisiran was consistent with that observed previously. The most common AE was infusion-relation reactions (14.1% of patients).


This interim analysis of the OLE study of the APOLLO-B trial showed that continued use of patisiran over 18 months resulted in preserved benefit for 6-MWT, KCCQ-OS, NT-proBNP and troponin I in patients with ATTR cardiac amyloidosis. Patients who were originally randomized to placebo and who started patisiran in the OLE period showed slowing or stabilization of disease progression.

‘However, these crossover patients did not recover the functional capacity or health status and QoL that were lost during the double-blind period relative to those in the patisiran group, highlighting the importance of early treatment initiation’, said the presenter Marianna Fontana.

There were no new safety concerns with the use of patisiran through 18 months, demonstrating a acceptable safety profile.

- Our coverage of ESC Heart Failure 2023 is based on the information provided during the congress –

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