Alnylam Presents New Clinical Research Findings at the Second European Meeting of ATTR Amyloidosis for Doctors and Patients

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today shared new findings at the Second European Meeting of ATTR Amyloidosis (EU-ATTR) for Doctors and Patients, being held September 2-3, in Berlin, Germany. The Company and collaborators presented results from a proteome-wide biomarker analysis of samples from the APOLLO Phase 3 study of ONPATTRO (patisiran), an RNAi therapeutic for the treatment of the polyneuropathy of hereditary ATTR (hATTR) amyloidosis in adults. In addition, results were presented from an analysis of the UK Biobank – a prospective cohort study with genetic, physical, and health data on approximately 500,000 individuals across the United Kingdom – on clinical outcomes and medical history of individuals with the non-pathogenic transthyretin (TTR) “stabilizing” T119M variant.

“These new clinical research findings provide important insights on a potential biomarker for monitoring polyneuropathy and response to treatment, and highlight human genetic data showing no evidence for protection against vascular disease or life-extending advantages of a ‘stabilizing’ T119M gene variant associated with elevated TTR plasma levels,” said Eric Green, Senior Vice President and General Manager, TTR Program at Alnylam. “Notably, our biomarker study represents the most comprehensive plasma proteomics analysis in patients with hATTR amyloidosis performed to date and the first system-wide proteomics interrogation of response to an RNAi therapeutic in humans. We believe a biomarker such as NfL could have the potential to allow for an earlier diagnosis of polyneuropathy in patients with hATTR amyloidosis.”

Biomarker Analysis of APOLLO Patient Samples

A comprehensive proteomics analysis on plasma samples from patients in the APOLLO Phase 3 study was conducted to interrogate system-wide changes in the proteome in response to treatment and to identify potential biomarkers for early detection of disease. Across greater than 1000 proteins screened, a significant change was observed in the levels of 66 proteins following patisiran treatment (p less than 4.18×10^–5). Neurofilament light chain (NfL) – a well-described biomarker of neuroaxonal damage – was identified as having the greatest statistical significance (p equals 3.95×10^–21) for change relative to placebo over the 18-month study period. A correlation between changes in NfL levels and polyneuropathy, as determined by the mNIS+7 score, indicated that decreasing levels of NfL are associated with improvements in measures of polyneuropathy. Thus, these data support further evaluation of NfL as a potential biomarker for hATTR amyloidosis that may facilitate earlier diagnosis of polyneuropathy and enable monitoring of disease progression and/or regression over time, with or without treatment. Moreover, upon further evaluation, NfL may also offer an easy and convenient blood test to detect polyneuropathy in patients with mutations that predominantly cause cardiomyopathy, e.g., V122I, but where underlying nerve damage often occurs and can be overlooked.