Nex-z trial for FAP to complete enrollment earlier than expected
Phase 3 results, if positive, will support applications seeking therapy's approval
A Phase 3 clinical trial testing Intellia Therapeutics’ gene-editing therapy nexiguran ziclumeran (nex-z) in adults with familial amyloid neuropathy (FAP) is ahead of its planned enrollment schedule, with recruitment now expected to be completed in the first half of 2026.
That’s according to a press release from Intellia announcing the latest financial results and company updates.
The MAGNITUDE-2 trial (NCT06672237) is currently recruiting up to 50 patients, ages 18 to 85, at sites in Argentina, Australia, Brazil, New Zealand, Singapore, and Taiwan. Participants will be randomly assigned to receive a one-time dose of either nex-z or a placebo and be followed for about 1.5 years.
Should results from this Phase 3 trial be positive, they will be used to support regulatory applications seeking the therapy’s approval for FAP.
The company will also present extended data from nex-z-treated FAP participants in the ongoing Phase 1 trial (NCT04601051) at the 5th International ATTR Amyloidosis Meeting for Patients and Doctors, to be held next month in Baveno, Italy.
Nex-z expected to prevent TTR production
ATTR amyloidosis is a group of diseases in which the transthyretin (TTR) protein forms toxic clumps called amyloid fibrils that accumulate in tissues, causing damage.
Also known as hereditary ATTR amyloidosis with polyneuropathy, FAP is a hereditary form of the disease, meaning that genetic mutations are the underlying cause of the formation and accumulation of amyloid fibrils. Most commonly, these mutations occur in the TTR gene, which contains instructions for cells to produce TTR.
In FAP, toxic TTR clumps mainly form in peripheral nerves, or those outside of the brain and spinal cord, leading to nerve damage and neurological symptoms. In ATTR amyloidosis with cardiomyopathy (ATTR-CM), a form of ATTR amyloidosis that can be either inherited or non-hereditary, these aggregates mainly build up in the heart, causing heart damage.
Developed by Intellia and Regeneron Pharmaceuticals, nex-z uses the gene-editing technology CRISPR/Cas9 to inactivate the TTR gene in liver cells, where most TTR production occurs. The therapy, formerly known as NTLA-2001, is therefore expected to prevent TTR production and subsequent accumulation of amyloid fibrils, potentially easing symptoms of FAP and ATTR-CM.
Improvements seen in nerve-damage-related impairment
The ongoing Phase 1 trial is evaluating the safety and preliminary efficacy of escalating doses of the experimental therapy in adults with FAP or ATTR-CM.
Previously reported results, covering 36 FAP participants who received an into-the-vein infusion of nex-z, showed that doses of at least 0.3 mg/kg resulted in a rapid and sustained drop in blood TTR levels. Specifically, these participants showed a TTR level reduction of about 90% a month after dosing, with levels largely unchanged through two years.
Thirteen out of 18 participants with two-year data on the Modified Neuropathy Impairment Score +7 (mNIS+7), a measure of nerve damage-related impairment, also saw clinically meaningful improvements.
Nex-z was generally safe and well tolerated, with mild or moderate reactions at the infusion site as the most common side effects.
Similarly, nex-z-treated ATTR-CM patients saw reductions in TTR levels and favorable changes in markers of heart function. Safety results were comparable to FAP participants.
MAGNITUDE-2 saw its first patient dosed in April and is testing nex-z against a placebo in a larger group of adults with FAP. The primary goal is to assess changes in blood TTR levels 29 days after the single dose and changes in mNIS+7 after 18 months, or 1.5 years.
Secondary goals include changes in blood TTR levels, life quality 18 months after the infusion, and the modified body mass index, which is a measure of clinical frailty and nutritional status.
Another global Phase 3 trial, called MAGNITUDE (NCT06128629), is testing the gene-editing therapy in up to 765 adults with ATTR-CM.
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