Examine neurofilament light chain (NfL) levels in patients with hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy from the Phase 3 APOLLO and HELIOS-A studies to assess the potential utility of NfL as a biomarker of disease progression.

NfL levels were measured using the Quanterix® Simoa^TM platform in healthy controls and patients with hATTR amyloidosis with polyneuropathy who participated in the APOLLO or HELIOS-A studies, gave consent, and had sufficient samples. The samples analyzed were from baseline, 21 days, 4 months, and 18 months in APOLLO, and baseline, 43 days, 4 months, 9 months, and 18 months in HELIOS-A.

At baseline, NfL levels were slightly higher in APOLLO than in HELIOS-A (69.4 pg/mL and 58.2 pg/mL, respectively) and did not differ significantly between treatment groups within each study. In the APOLLO placebo arm, NfL levels significantly increased vs baseline at 4 months (+19.0 pg/mL, p<0.001) and at 18 months (+36.3 pg/mL, p<0.001). In the APOLLO patisiran arm, NfL levels decreased significantly at 4 months and 18 months vs baseline (-20.4 pg/mL and -23.2 pg/mL respectively; p<0.001 for both). In HELIOS-A, NfL levels in patisiran and vutrisiran groups significantly decreased vs baseline at 4 months (-9.7 pg/mL and -11.0 pg/mL, respectively; p<0.05 for both) and at 18 months (-16.4 pg/mL and -19.9 pg/mL, respectively; p<0.001 for both).

NfL levels significantly decreased from baseline with patisiran and vutrisiran as early as 4 months after treatment initiation and decreased levels were maintained through 18 months. In contrast, NfL levels in untreated patients increased significantly. These results suggest that NfL is potentially useful for monitoring treatment response and disease progression in patients with hATTR amyloidosis with polyneuropathy.