Previously referred to as NTLA-2001, nex-z is an in vivo ‘CRISPR-based’ therapy. Credit: Volha_R/Shutterstock.

Intellia Therapeutics has commenced subject dosing in the randomised pivotal Phase III MAGNITUDE-2 trial of nexiguran ziclumeran (nex-z) for hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN).

This global trial builds on Phase I data indicating that nex-z, with a single dose, can significantly decrease serum transthyretin (TTR) levels.

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It is a double-blind, placebo-controlled trial tailored to assess the safety and efficacy of nex-z in approximately 50 ATTRv-PN subjects.

Adult participants with this condition will be randomised to receive either one 55mg infusion of the therapy or a placebo, with the primary endpoint being a modified neuropathy impairment score and serum TTR level changes.

Intellia Therapeutics CEO and president John Leonard said: “This milestone marks important progress toward our goal of completing the MAGNITUDE-2 clinical programme, and we are optimistic the study will enable us to demonstrate nex-z’s potential to be the first to halt or reverse disease progression with a single dose in hereditary ATTR with polyneuropathy.”

Previously referred to as NTLA-2001, nex-z is an in vivo ‘CRISPR-based’ therapy designed to inactivate the TTR gene encoding for the mutated TTR protein that leads to polyneuropathy.

It has received advanced therapy designation for polyneuropathy and cardiomyopathy from the US Food and Drug Administration (FDA), as well as orphan drug status from the European Commission and the FDA.

Intellia anticipates presenting the therapy’s Phase I trials’ longer-term data for both cardiomyopathy and polyneuropathy later in the year.

The company is also planning to submit a biologics licensing application (BLA) for the therapy in ATTRv-PN by 2028.

It is leading the development and commercialisation of nex-z in a ‘multi-target discovery, development, and commercialisation’ partnership with Regeneron.

Last October, Intellia announced positive outcomes from its Phase I/II trial of NTLA-2002, a CRISPR-based gene editing therapy targeting hereditary angioedema (HAE).