Patisiran: Use in Patients with Renal Impairment

Patisiran: Use in Patients with Renal Impairment

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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

Post‑Hoc Analysis in Patients with ATTR and CKD – Pooled Safety Population – Global Safety Database – Label Information – Abbreviations – References

 Post-Hoc Analysis in Patients with ATTR and CKD

A post-hoc analysis was conducted to evaluate the efficacy and safety of patisiran in patients with ATTR with and without comorbid mild to moderate CKD. Data were used from the following patisiran clinical trials2:

      The Phase 3 APOLLO study, a randomized, double-blind, placebo-controlled study in patients with hATTR-PN4

      The Phase 3 APOLLO‑B study, a randomized, double-blind, placebo-controlled study in patients with ATTR-CM, including both hATTR and wtATTR5

      The Phase 3b, open-label study in patients with hATTR-PN who had disease progression post-OLT6

      The Phase 2 OLE study in patients with hATTR-PN who completed the patisiran Phase 2 study7

      The Global OLE study in patients with hATTR-PN who completed the Phase 2 OLE or APOLLO studies.8

A total of 634 patients were included in the analysis. Overall, 158 (24.9%) patients had a baseline eGFR <60 mL/min/1.73m2. Select baseline characteristics of patients across all studies are presented in Table 1.2

Table 1. Baseline eGFR Across Patisiran Clinical Studies.2

Efficacy Results

During treatment with patisiran, mean eGFR remained relatively stable over time regardless of baseline kidney function (Figure 1).2

Figure 1. Change in Mean eGFR Over Time by Baseline eGFR Subgroups.2

Treatment with patisiran resulted in serum TTR knockdown that was consistent and maintained across the studies, regardless of baseline eGFR (Figure 2).2

Figure 2. Serum TTR Knockdown by Baseline eGFR.2

Safety Results

Safety with patisiran treatment was assessed in patients with baseline eGFR <60 mL/min/1.73m2, and no new safety signals were observed. Renal and urinary AEs reported across the studies are presented in Table 2 and Table 3.2

Table 2. Renal and Urinary AEs in Patients with hATTR‑PN and Baseline eGFR <60 mL/min/1.73m2.2

Table 3. Renal and Urinary AEs in Patients with hATTR-CM and Baseline eGFR <60 mL/min/1.73m2.2

 Pooled Safety Population

In a pooled safety population analysis (N=224) including data from the completed Phase 2 OLE, completed Phase 3 APOLLO, and Global OLE (as of January 27, 2021) studies, 48 (21.4%) patients had mild renal impairment, 22 (9.8%) patients had moderate renal impairment, and 1 (0.4%) patient had severe renal impairment at baseline. Patients with severe renal impairment were excluded from patisiran clinical trials. No renal safety concerns have been reported in the patisiran clinical trials. No increased risk of adverse events was associated with administration of patisiran to patients with mild or moderate renal impairment (eGFR ≥30 to <90 mL/min/1.73m2), and no dose adjustments were necessary.3

 Global Safety Database

A cumulative post-marketing review of Alnylam Pharmaceuticals’ global safety database did not identify any new safety concerns with the use of patisiran in patients with a history of severe renal impairment or ESRD. Use in patients with severe renal impairment or ESRD will continue to be closely monitored by Alnylam through routine pharmacovigilance activities.3

 ONPATTRO prescribing information – Relevant content

The USE IN SPECIFIC POPULATIONS section provides the following information1:

Renal Impairment

No dose adjustment is necessary in patients with mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] ≥30 to <90 mL/min/1.73m2). ONPATTRO has not been studied in patients with severe renal impairment or end-stage renal disease.

The CLINICAL PHARMACOLOGY section provides the following information1:

Pharmacokinetics

Specific Populations

Age, race (non-Caucasian vs. Caucasian), sex, and prior liver transplantation had no impact on the steady state pharmacokinetics of patisiran or TTR reduction. Population pharmacokinetic and pharmacodynamic analyses indicated no impact of mild or moderate renal impairment (eGFR ≥30 to <90 mL/min/1.73m2) or mild hepatic impairment (bilirubin ≤1 x ULN and AST >1 x ULN, or bilirubin >1.0 to 1.5 x ULN) on patisiran exposure or TTR reduction. ONPATTRO has not been studied in patients with severe renal impairment, end-stage renal disease, or moderate or severe hepatic impairment.

 Abbreviations

ΑE = adverse event; AKI = acute kidney injury; AST = aspartate transaminase; ATTR = transthyretin amyloidosis; ATTR‑CM = transthyretin amyloidosis with cardiomyopathy; CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; ESRD = end stage renal disease; hATTR = hereditary transthyretin amyloidosis; hATTR‑CM = hereditary transthyretin amyloidosis with cardiomyopathy; hATTR‑PN = hereditary transthyretin amyloidosis with polyneuropathy; OLE = open-label extension; OLT = orthotopic liver transplant; PY = patient-year; TTR = transthyretin; ULN = upper limit of normal; wtATTR = wild-type transthyretin amyloidosis.

Updated 1 August 2025

 References

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

2.  Dang J, Labeyrie C, Bender S, et al. Effect and safety of patisiran in patients with hereditary transthyretin amyloidosis with polyneuropathy and chronic kidney disease. Presented at: International Symposium on Amyloidosis (ISA); May 26-30, 2024; Rochester, MN, USA.

3.  Alnylam Pharmaceuticals. Data on file. MED-ALL-TTR02-2400049.

4.  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

5.  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

6.  Schmidt HH, Wixner J, Planté‐Bordeneuve V, et al. Patisiran treatment in patients with hereditary transthyretin‐mediated amyloidosis with polyneuropathy after liver transplantation. Am J Transplant. 2022;22(6):1646-1657. doi:10.1111/ajt.17009

7.  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

8.  Adams A, Polydefkis M, González-Duarte A, et al. Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study. Lancet Neurol. 2021;20(1):49-59. doi:10.1016/S1474-4422(20)30368-9