Patisiran: Serum Transthyretin Levels

Patisiran: Serum Transthyretin Levels

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The full Prescribing Information for ONPATTRO® (patisiran) is provided here. Alnylam Pharmaceuticals does not recommend the use of its products in any manner that is inconsistent with the approved Prescribing Information. This resource may contain information that is not in the approved Prescribing Information.

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 Summary

Index

Clinical Data – Label Information – Abbreviations – References

 Clinical Data

Phase 2 OLE

The Phase 2 OLE study (N=27) was a multicenter, international study in patients with hATTR-PN. Patients who previously received and tolerated patisiran in the Phase 2 study were eligible to enroll in the Phase 2 OLE study. Patients received IV patisiran 0.3 mg/kg every 3 weeks for approximately 2 years.1

In the Phase 2 OLE, serum TTR was used as a biomarker for PD assessment. Over 24 months, the mean percent reduction from baseline in serum TTR level was 82%, with a mean maximal reduction of 93%. Concomitant TTR stabilizer use (patisiran and TTR stabilizer or patisiran alone), TTR genotype (V30M or non-V30M), sex, and age (<65 or ≥65 years) did not affect the PD activity of patisiran.1

APOLLO Study

APOLLO was a multicenter, international, randomized (2:1), double-blind, placebo-controlled, phase 3 study designed to assess the efficacy and safety of IV patisiran 0.3 mg/kg every 3 weeks (n=148) versus placebo (n=77) in patients with hATTR-PN. The primary endpoint was the change from baseline in the mNIS+7 at 18 months.2

In the APOLLO study, serum TTR was used as a biomarker for PD assessment. In the patisiran group, a reduction in serum TTR was observed from baseline to Week 3 and sustained over a period of 18 months (Figure 1), and the median percent reduction from baseline in serum TTR level during the 18 months was 81% (range, -38% to 95%) and was similar across age, sex, or genotype.2

Figure 1. Mean (± SEM) Percent Change from Baseline in Serum TTR Over Time in APOLLO.2

Global OLE

The Global OLE study (N=211) was a multicenter, international study designed to evaluate the long-term safety and efficacy of IV patisiran in patients with hATTR-PN. Patients with hATTR-PN who completed the patisiran Phase 2 OLE study or phase 3 APOLLO study and met eligibility criteria were able to start or continue IV patisiran 0.3 mg/kg every 3 weeks for up to 5 years. The study enrolled 25 patients from the patisiran Phase 2 OLE study (Phase 2 OLE-patisiran group), 137 patients from the APOLLO-patisiran arm (APOLLO-patisiran group), and 49 patients from the APOLLO-placebo arm (APOLLO-placebo group).6

In the Global OLE study, serum TTR was used as a biomarker for PD assessment. A reduction in median serum TTR levels was observed by the first measurement timepoint, decreasing by 84.3% at Week 26 (range, 97.4% to 6.3%) and 88.2% by Week 52 (range, 97.0% to 25.9%) in the APOLLO-placebo group (Figure 2).3

Figure 2. Mean (± SEM) Percent Change from Parent Study Baseline in Serum TTR Over 5 Years in the Global OLE.3

APOLLO-B Study

APOLLO-B was a multicenter, randomized (1:1), double-blind, placebo-controlled, phase 3 study designed to evaluate the efficacy and safety of IV patisiran 0.3 mg/kg every 3 weeks (n=181) versus placebo (n=179) in patients with ATTR-CM, including both hATTR and wtATTR. The primary endpoint was the change from baseline in the 6-MWT at 12 months. After the 12-month double-blind treatment period, all patients received patisiran in an OLE period.4

In the APOLLO-B study, serum TTR was used as a biomarker for PD assessment. At baseline, the mean serum TTR level was 235.32 mg/L (SD, 68.05 mg/L) in the patisiran arm and 244.77 mg/L (SD, 73.17 mg/L) in the placebo arm. At 12 months, the mean serum TTR level was 30.93 mg/L (SD, 33.60 mg/L) in the patisiran arm and 229.40 mg/L (SD, 77.15 mg/L) in the placebo arm. In the patisiran arm, the mean percent reduction from baseline in serum TTR level was 86.8% (SD, 13.6%) at 12 months.4

HELIOS-A Study

HELIOS-A was a phase 3, global, randomized, open-label study designed to evaluate the efficacy and safety of vutrisiran in patients with hATTR-PN. Patients were randomized (3:1) to receive either vutrisiran 25 mg every 3 months by subcutaneous injection (n=122) or patisiran 0.3 mg/kg every 3 weeks by IV infusion (as a reference group, n=42) for 18 months. This study used the placebo arm of the APOLLO study as an external control arm (n=77) for the primary endpoint and most other efficacy endpoints. The primary endpoint was the change from baseline in mNIS+7 at 9 months.7

In the HELIOS-A study, serum TTR was used as a biomarker for PD assessment. Noninferiority of the percent reduction from baseline in serum TTR levels over 18 months in the vutrisiran arm compared with the within-study patisiran arm was evaluated as a secondary endpoint.7 In patients treated with patisiran, the steady-state peak and trough mean percent reduction from baseline in serum TTR levels over 18 months was 86.0% (SD, 10%) and 74.7% (SD, 14.7%), respectively.5

ONPATTRO Prescribing Information – Relevant Content

For relevant labeling information, please refer to the following sections of the ONPATTRO Prescribing Information8:

         CLINICAL PHARMACOLOGY Section 12.1 Mechanism of Action

         CLINICAL PHARMACOLOGY Section 12.2 Pharmacodynamics

 Abbreviations

6-MWT = 6-minute walk test; ATTR‑CM = transthyretin amyloidosis with cardiomyopathy; ELISA = enzyme-linked immunosorbent assay; hATTR = hereditary transthyretin amyloidosis; hATTR-PN = hereditary transthyretin amyloidosis with polyneuropathy; IV = intravenous; mNIS+7 = modified Neuropathy Impairment Score +7; OLE = open-label extension; PD = pharmacodynamic; SD = standard deviation; SEM = standard error of the mean; TTR = transthyretin; wtATTR = wild-type transthyretin amyloidosis.

Updated 25 September 2025

References

1.  Coelho T, Adams D, Conceição I, et al. A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. Orphanet J Rare Dis. 2020;15(1). doi:10.1186/s13023-020-01399-4

2.  Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med. 2018;379(1):11-21. doi:10.1056/NEJMoa1716153

3.  Supplement to: Adams D, Wixner J, Polydefkis M, et al. Five-year results with patisiran for hereditary transthyretin amyloidosis with polyneuropathy: A randomized clinical trial with open-label extension. JAMA Neurol. 2025;82(3):228-236. doi:10.1001/jamaneurol.2024.463

4.  Maurer MS, Kale P, Fontana M, et al. Patisiran treatment in patients with transthyretin cardiac amyloidosis. N Engl J Med. 2023;389(17):1553-1565. doi:10.1056/NEJMoa2300757

5.  Supplement to: Adams D, Tournev IL, Taylor MS, et al. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid. 2023;30(1):18-26. doi:10.1080/13506129.2022.2091985

6.  Adams D, Wixner J, Polydefkis M, et al. Five-year results with patisiran for hereditary transthyretin amyloidosis with polyneuropathy: A randomized clinical trial with open-label extension. JAMA Neurol. 2025. doi:10.1001/jamaneurol.2024.4631.

7.  Adams D, Tournev IL, Taylor MS, et al. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid. 2023;30(1):18-26. doi:10.1080/13506129.2022.2091985

8.  ONPATTRO (patisiran) Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.