This activity was funded by Alnylam Pharmaceuticals. The medical content was developed independently by M3 and Professor Violaine Planté-Bordeneuve.

Highlights from

Amyloidosis Conferences



Outcomes with patisiran in patients with hATTR amyloidosis with polyneuropathy post-orthotopic liver transplantation

Take-home messages
  • Patisiran reduced serum TTR levels from baseline through 6 months of treatment in patients with hATTR amyloidosis and disease progression post-OLT
  • Efficacy and safety of patisiran for hATTR post-OLT were consistent with the results observed in the phase III APOLLO study

Hereditary transthyretin-mediated (hATTR) amyloidosis is a debilitating, potentially fatal disease caused by the aggregation of misfolded transthyretin (TTR) variants that lead to the formation of amyloid fibrils.1-3 Orthotopic liver transplantation (OLT) is a treatment option for hATTR amyloidosis that removes almost all of the circulating variant TTR, and slows disease progression in the early stages of disease. However, the continued deposition of wild-type TTR on existing amyloid fibrils in the nerves and heart can lead to progressive neurologic and cardiologic impairment post-OLT, and treatment options for these patients are limited.3-5

Patisiran is an RNA interference (RNAi) therapeutic that reduces serum TTR levels by inhibiting the hepatic production of variant and wild-type TTR.3,6 It was approved for the treatment of hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy following the results of the phase III placebo-controlled APOLLO study, which showed that patisiran could halt or reverse polyneuropathy and improve quality of life for most patients.7

The patisiran post-OLT open-label study, conducted across seven European countries, is investigating the efficacy and safety of 0.3 mg/kg intravenous patisiran, once every 3 weeks for 12 months, in the treatment of patients with hATTR amyloidosis with polyneuropathy and disease progression post-OLT (N=23). On average, patients received an OLT 3.8 years after diagnosis and received their first dose of patisiran 9.4 years post-OLT. The primary endpoint is the average of the Month 6 and Month 12 TTR percent reduction (from baseline) and the safety endpoint is the frequency of adverse events.

The 6-month interim analysis of the study, presented in a poster at this year's American Academy of Neurology (AAN) Virtual Annual Meeting, found that patisiran treatment caused a rapid and durable reduction in serum TTR levels versus baseline. At Month 6, serum TTR levels had reduced by an average of 89.2% versus baseline (202.1 mg/L at baseline vs 21.2 mg/L at Month 6).

All patients had experienced at least one adverse event (AE) by Month 6. The majority of these were mild or moderate, and the common AEs were consistent with those reported in APOLLO.7 Five patients reported a total of six serious AEs (hip break and heart failure (HF), cholangitis, transplant rejection, HF and infusion-related reaction; transplant rejection was likely due to insufficient immunosuppression and the patient remains on study drug). Only one serious AE (infusion-related reaction) was considered treatment-related. No deaths occurred.

These interim results suggest that patisiran RNAi therapy may be effective in reducing disease progression in patients with hATTR with polyneuropathy post-OLT, consistent with patients who had not undergone OLT in the APOLLO study.

Based on Coelho T, Gillmore J D et al. Open-label study of patisiran in patients with hATTR amyloidosis post-orthotopic liver transplant. Poster presented at the American Academy of Neurology (AAN) Virtual Annual Meeting, 17-22 April, 2021

  1. Benson M D, Dasgupta N R, Rao R. Diagnosis and screening of patients with hereditary transthyretin amyloidosis (hATTR): current strategies and guidelines. Ther Clin Risk Manag 2020;16:749-758
  2. Hawkins P N, Ando Y et al. Evolving landscape in the management of transthyretin amyloidosis. Ann Med 2015;47(8):625-638
  3. Suhr O B, Coelho T et al. Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study. Orphanet J Rare Dis 2015;10:109
  4. Ando Y, Coelho T et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis 2013;8:31
  5. Liepnieks J J, Benson M D. Progression of cardiac amyloid deposition in hereditary transthyretin amyloidosis patients after liver transplantation. Amyloid 2007;14(4):277-282
  6. Coelho T, Adams D et al. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med 2013;369(9):819-829
  7. Adams D, Gonzalez-Duarte A et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med 2018;379(1):11-21

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