Intellia Therapeutics announces longer-term Phase 1 data for nex-z

Intellia Therapeutics (NTLA) announced longer-term follow-up data from the ongoing Phase 1 study of investigational nexiguran ziclumeran for the treatment of hereditary ATTR amyloidosis with polyneuropathy. 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. 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, the mean serum TTR reduction at 24 months was 92%. Among the 12 patients who had reached 36 months of follow-up, the mean serum TTR reduction was 90%. 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, modified Neuropathy Impairment Score +7, modified body mass index, Norfolk Quality of Life-Diabetic Neuropathy questionnaire, neurofilament light chain, and polyneuropathy disability score. Among the 18 patients in whom a 24-month mNIS+7 assessment was completed by the data cutoff date, 13 showed improvements of a clinically meaningful threshold of greater than or equal to4 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. 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 greater than3 liver enzyme elevations that were not considered serious, were asymptomatic and resolved spontaneously without medical intervention or sequelae.