- One dose of nex-z led to rapid, deep and durable TTR reductions, with mean reductions of at least 90% from baseline sustained through three years
- Stabilization or improvement in disease-related clinical measures observed at 24 months
- Continue to observe generally favorable safety data with no new drug-related events within the follow-up period
- Data presented today at the 5th International ATTR Amyloidosis Annual Meeting for Patients and Doctors with simultaneous publication in the New England Journal of Medicine
- Expect to complete enrollment in multi-national Phase 3 MAGNITUDE-2 trial in first half 2026 to support a potential BLA filing by 2028
CAMBRIDGE, Mass., Sept. 25, 2025 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, today announced longer-term follow-up data from the ongoing Phase 1 study of investigational nexiguran ziclumeran (nex-z) for the treatment of hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). Results were presented in an oral session on Thursday, September 25 at the 5th International ATTR Amyloidosis Annual Meeting for Patients and Doctors in Baveno, Italy. The results were simultaneously published in the New England Journal of Medicine, and the presentation will be available on the Scientific Publications & Presentations section of intelliatx.com.
"After receiving a one-time treatment of nex-z, patients continue to experience durable TTR reductions, including those who have reached three years of follow-up,” said Intellia President and Chief Executive Officer John Leonard, M.D. “The results from our ongoing Phase 1 study of nex-z support our belief that deeper and more consistent reductions in TTR translate to better outcomes for patients. Our Phase 3 MAGNITUDE-2 study is progressing swiftly, and we are eagerly anticipating the results, which we believe will demonstrate nex-z’s potential to halt or reverse disease progression in people living with ATTRv-PN.”
Continuation of Deep and Durable Serum TTR Reduction
Deep, durable and consistent TTR reductions continue to be observed. Across patients who received a one-time dose of 0.3 mg/kg or higher (n=33), the mean serum TTR reduction at 24 months was 92% (corresponding mean absolute serum TTR level of 17.3 g/mL [Mean 95% CI, 12.5 – 22.2]). Among the 12 patients who had reached 36 months of follow-up, the mean serum TTR reduction was 90% (corresponding mean absolute serum TTR level of 20 g/mL [Mean 95% CI, 11.2 – 28.8]).
Evidence of Stability or Improvement on Clinical and Biomarker Measures
Favorable trends indicating stability or improvement were observed in most patients with ATTRv-PN after a single dose of nex-z. Stability or improvement was based on evaluation of multiple clinical and biomarker measures, including Neuropathy Impairment Score (NIS), modified Neuropathy Impairment Score +7 (mNIS+7), modified body mass index (mBMI), Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) questionnaire, neurofilament light chain (NfL), and polyneuropathy disability (PND) score.
Among the 18 patients in whom a 24-month mNIS+7 assessment was completed by the data cutoff date (April 11, 2025), 13 (72%) showed improvements of a clinically meaningful threshold of ≥4 points, including most of the patients in the cohort who had progressed on patisiran. Among all 36 patients enrolled in the Phase 1 trial, mean values of the secondary endpoints mBMI, QoL-DN and NfL all trended toward disease improvement and 89% of patients showed improvement or stability in PND scores through 24 months compared to baseline.
Safety Summary
Nex-z has been generally well tolerated as of the data cutoff date across all patients and at all dose levels tested. The most commonly reported treatment-related adverse events were infusion-related reactions, which were mild or moderate and did not result in any discontinuations. As previously reported, three participants had Grade >3 liver enzyme elevations that were not considered serious, were asymptomatic and resolved spontaneously without medical intervention or sequelae.
Phase 3 MAGNITUDE-2 Trial Advancing Rapidly
Intellia began dosing patients in the Phase 3 MAGNITUDE-2 trial in April 2025. Patient screening is advancing rapidly, and enrollment completion is expected in the first half of 2026. Intellia anticipates submitting a biologics license application (BLA) for ATTRv-PN by 2028. MAGNITUDE-2 is a randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of nexiguran ziclumeran (nex-z) in approximately 50 patients with hereditary transthyretin ATTR amyloidosis with polyneuropathy (ATTRv-PN). The primary endpoints of the study are a change in modified neuropathy impairment score and a change in serum TTR levels. Adult patients with ATTRv-PN are randomized 1:1 to receive a single 55 mg infusion of nex-z or placebo. For more information on MAGNITUDE-2 (NCT06672237), please visit clinicaltrials.gov.
About the Nexiguran Ziclumeran (nex-z) Phase 1 Clinical Trial
The global Phase 1 trial is an ongoing open-label, multi-center, two-part study of nex-z in adults with hereditary transthyretin ATTR amyloidosis with polyneuropathy (ATTRv-PN) or transthyretin ATTR amyloidosis with cardiomyopathy (ATTR-CM). Part 1 of the ATTRv-PN arm of the study is an open-label, single-ascending dose escalation cohort and Part 2 is an open-label, single-dose expansion cohort. Visit clinicaltrials.gov (NCT04601051) for more details.