Rare Disease Report

Sneak Peak at the 24 Month Patisiran Amyloidosis Study

JULY 01, 2016
James Radke, PhD
Just got a sneak peak of the data Alnylam will be presenting next week at the XV International Symposium on Amyloidosis in Uppsala, Sweden. And the data is impressive for patisiran, their RNAi drug they have in development to treat hereditary TTR-mediated amyloidosis (hATTR amyloidosis).

What is hereditary TTR-mediated amyloidosis (hATTR amyloidosis)

Hereditary transthyretin (TTR)-mediated amyloidosis (hATTR amyloidosis) is an inherited, progressively debilitating, and often fatal disease caused by mutations in the TTR gene. TTR protein is produced primarily in the liver and is normally a carrier of vitamin A. Mutations in TTR cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy.

Two forms of the condition can be separated based on the damaged, either towards neural tissue [familial amyloidotic polyneuropathy (FAP)] or cardiac tissue – [familial amyloidotic cardiomyopathy (FAC)]. Patients with FAP have a life expectancy of 5-15 years following symptom onset whereas patients with FAC live 2.5 – 5 years following symptom onset (if left untreated).

Open Label Phase 2 Study

In the patisiran single-arm Phase 2 open label extension study, data from 24 patients who have been treated with patisiran (0.3 mg/kg by intravenous infusion every 3 weeks) for 24 months showed the drug to be safe.   

More specifically, the majority of the adverse events were mild or moderate with only 6 patients reporting a severe adverse event and all 6 were unrelated to the drug.

Regarding the drug efficacy, data shows that patisiran does reduce serum TTR knockdown and that coincides with a mean decrease of 6.7 points from baseline in mNIS+7.
mNIS+7 is an evaluation of muscle weakness, sensory and autonomic function, and nerve conductance, where neuropathy progression leads to an increased score over time.
The efficacy data compares favorably with historical data that would estimate a mean increase in mNIS+7 of 26 to 30 points after 24 months in untreated hATTR-PN patients.

In a news release, Eric Green, Vice President, General Manager, TTR Program at Alnylam said, “With patisiran, we believe the mean 6.7 point decrease in mNIS+7 seen over 24 months is a promising result in light of the rapid increase in neuropathy impairment scores that would have been anticipated based on analyses of other historical data sets. Moreover, we’re encouraged to see that individual patient mNIS+7 responses show evidence for halting of or improvement in neuropathy progression in over 70% of patients.”
Green added, “Accordingly, we look forward to reporting data from the APOLLO Phase 3 trial with patisiran in mid-2017, where, in addition to evaluating the effect on neuropathy progression, we also expect to evaluate patisiran’s impact on other aspects of the disease, including cardiac manifestations, given the significant number of patients enrolled in the trial with cardiac involvement.”
To see the slides being presented at the XV International Symposium on Amyloidosis , click here.

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