Intellia Announces First Clinical Evidence from Ongoing Phase 1 Study that Nexiguran Ziclumeran (nex-z), an In Vivo CRISPR/Cas9-Based Gene Editing Therapy, May Favorably Impact Disease Progression in Transthyretin (ATTR) Amyloidosis

Core Insights - Intellia Therapeutics announced positive clinical data from the Phase 1 trial of nexiguran ziclumeran (nex-z) for treating transthyretin (ATTR) amyloidosis, indicating that significant reductions in serum TTR levels may correlate with clinical benefits in patients [1][3][15] ATTR-CM Arm Results - A single dose of nex-z resulted in a mean serum TTR reduction of 90% at month 12, with a mean residual serum TTR concentration of 17 µg/mL [4] - Patients showed evidence of disease stabilization or improvement across multiple cardiac disease progression markers at month 12, despite a high proportion of advanced heart failure cases [4][5] - 92% of patients demonstrated stability or improvement in their NYHA functional classification, with all patients classified as NYHA Class III at baseline showing improvement or no change at month 12 [5] ATTRv-PN Arm Results - In patients receiving a dose of 0.3 mg/kg or higher, the mean serum TTR reduction was 91% at month 12, with a mean residual serum TTR concentration of 20 µg/mL [8] - Favorable trends indicating stability or improvement were observed in clinical measures such as Neuropathy Impairment Score (NIS) and modified Neuropathy Impairment Score (mNIS+7) [8][9] Safety Profile - Nex-z was generally well tolerated, with infusion-related reactions being the most commonly reported treatment-related adverse events, which were predominantly mild to moderate [7][10] Future Studies - The ongoing Phase 3 MAGNITUDE study aims to evaluate the efficacy and safety of nex-z in approximately 765 patients with ATTR-CM, focusing on cardiovascular-related mortality and events [13] - The MAGNITUDE-2 study will assess the efficacy and safety of nex-z in 50 adults with ATTRv-PN, with primary endpoints including changes in modified Neuropathy Impairment Score +7 [14]