The U.S. Food and Drug Administration (FDA) on Tuesday said it removed the clinical hold on Intellia Therapeutics Inc.‘s (NASDAQ:NTLA) Investigational New Drug application (IND) for the MAGNITUDE-2 Phase 3 trial of nexiguran ziclumeran (nex-z) for hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN).
ATTRv-PN is a rare, fatal, autosomal dominant progressive disease where misfolded transthyretin proteins form amyloid deposits in peripheral nerves, causing sensory and motor dysfunction.
The company has aligned with the FDA on certain study modifications and mitigation measures related to MAGNITUDE-2 that include enhanced safety monitoring of liver laboratory tests.
Why It Matters?
As part of the protocol amendment, Intellia has increased the trial’s target enrollment from approximately 50 patients to approximately 60 patients.
The primary endpoints of the study are a change in modified neuropathy impairment score and a change in serum TTR levels.
In September 2025, Intellia Therapeutics released longer-term follow-up data from the ongoing Phase 1 study of investigational nexiguran ziclumeran (nex-z) for ATTRv-PN.
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.
The clinical holds on the INDs for MAGNITUDE and MAGNITUDE-2 were imposed by the FDA in October 2025, following the observation of Grade 4 liver transaminases and increased total bilirubin in a patient who was dosed with nex-z in MAGNITUDE that met the trial’s protocol-defined pausing criteria.
Intellia’s engagement with the FDA is ongoing regarding the clinical hold on the IND for the MAGNITUDE Phase 3 trial of nex-z for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The company plans to provide an update once alignment has been achieved on the path forward for this program.
Analyst Take
William Blair wrote, “We continue to believe in the efficacy of Intellia's platform, and 2026 will be a major year for the promising HAE program, but safety events from nex-z have been and will continue to be a stock overhang until further regulatory clarity is gained on resumption of MAGNITUDE and as investors gain comfort with new risk-mitigation strategies, in our view.”
Analyst Myles Minter maintains the Market Perform rating on Intellia, but is incrementally more positive that there is a regulatory path forward here for Intellia's platform more broadly.
Price Action: NTLA stock is up 9.53% at $15.28 at the last check on Tuesday, according to Benzinga Pro data.
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