Intellia Therapeutics announced positive two-year follow-up data from its Phase 1 trial of nexiguran ziclumeran (nex-z) for hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). The data, presented at the 2025 Peripheral Nerve Society Annual Meeting, demonstrated sustained reductions in transthyretin (TTR) protein levels and clinically meaningful improvements in disease-related outcomes. The company is also progressing with its Phase 3 MAGNITUDE-2 trial.
This news is important because it suggests that a single dose of nex-z could offer a durable and effective treatment for ATTRv-PN, a debilitating and fatal disease. The observed improvements in patients previously progressing on patisiran, a currently approved ATTRv-PN therapy, are particularly noteworthy and suggest nex-z may offer advantages over existing treatment options. This potential for a one-time curative treatment represents a significant advancement in the management of ATTRv-PN.
Two years after a single dose of nex-z, patients experienced a mean serum TTR reduction of 90%, which remained consistent throughout the follow-up period. Clinically meaningful improvements were observed in several measures, including the modified Neuropathy Impairment Score +7 (mNIS+7), with 14 out of 18 patients demonstrating improvement at 24 months. Importantly, this included 5 out of 6 patients who had previously experienced disease progression while on patisiran. The therapy also showed a generally favorable safety and tolerability profile with no new drug-related adverse events reported during the two-year period. The ongoing Phase 3 MAGNITUDE-2 trial aims to further evaluate the efficacy and safety of nex-z in a larger patient population, with potential for a Biologics License Application (BLA) submission by 2028.
These results reinforce the potential of nex-z as a one-time treatment for ATTRv-PN. The sustained TTR reduction and clinical improvements observed over two years, including in patients who had failed previous therapy, suggest a potential paradigm shift in the treatment landscape for this disease. Positive results from the MAGNITUDE-2 trial could lead to regulatory approval and ultimately provide patients with a more effective and convenient treatment option. This development may also spur further research into gene editing therapies for other rare and debilitating diseases.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
