Intellia Announces Positive Two-Year Follow-Up Data from Ongoing Phase 1 Study of Nexiguran Ziclumeran (nex-z), in Patients with Hereditary Transthyretin (ATTR) Amyloidosis with Polyneuropathy at Peripheral Nerve Society Annual Meeting

Core Insights - Intellia Therapeutics announced positive two-year follow-up data from the Phase 1 trial of investigational nexiguran ziclumeran (nex-z) for hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN) [1][2] - The data presented at the 2025 Peripheral Nerve Society Annual Meeting indicates that a single dose of nex-z leads to significant reductions in serum TTR levels and improvements in neuropathic impairment measures [2][5] ATTRv-PN Results - In the dose-escalation portion (N=15), the mean Neuropathy Impairment Score (NIS) improved by -2.0 at Month 12 and -4.5 at Month 24 [4] - In the dose expansion portion (N=21), the mean NIS improved by -2.1 at Month 12 and -5.2 at Month 24 [4] - The overall mean change in modified NIS +7 (mNIS+7) was -0.6 at Month 12 and -8.5 at Month 24 [4] - Among patients previously on patisiran, the mean mNIS+7 change was -6.3 at Month 12 and -6.5 at Month 24 [4] - The Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) score improved by -3.5 at Month 12 and -8.5 at Month 24 [4] - Neurofilament light chain (NfL) showed a reduction of -8.6% at Month 12 [4] Safety and Tolerability - Nex-z demonstrated generally favorable safety and tolerability with no new drug-related adverse events reported during the follow-up period [5][7] - The most common treatment-related adverse events were mild to moderate infusion-related reactions, which did not lead to discontinuations [7] Clinical Program and Future Prospects - The ongoing Phase 1 trial is a multi-center study evaluating nex-z in adults with hereditary ATTR amyloidosis [8] - The Phase 3 MAGNITUDE-2 trial is designed to measure clinical outcomes and evaluate the efficacy of a single dose of nex-z, with a potential biologics license application submission by 2028 [5][9] - Nex-z is based on CRISPR technology and aims to be the first one-time treatment for ATTR amyloidosis by inactivating the TTR gene [10]