Intellia Reports Positive Two-Year Follow-Up Data in Phase 1 ATTR Study

Rare Daily Staff

CRISPR-based therapy developer Intellia Therapeutics reported positive two-year follow-up data from the ongoing phase 1 trial of its experimental therapy for the treatment of hereditary ATTR amyloidosis with polyneuropathy, a rare disease that causes a buildup of amyloid in the body.

Results were presented May 18 at the 2025 Peripheral Nerve Society Annual Meeting in Edinburgh, United Kingdom.

Transthyretin amyloidosis, or ATTR amyloidosis, is a rare, progressive, and fatal disease. Hereditary ATTR (ATTRv) amyloidosis occurs when a person is born with mutations in the TTR gene, which causes the liver to produce structurally abnormal transthyretin (TTR) protein with a propensity to misfold. These damaged proteins build up as amyloid in the body, causing serious complications in multiple tissues, including the heart, nerves and digestive system.

ATTRv amyloidosis predominantly manifests as polyneuropathy (ATTRv-PN), which can lead to nerve damage, or cardiomyopathy (ATTRv-CM), which can lead to heart failure. Some individuals without the genetic mutation produce non-mutated, or wild-type, TTR proteins that become unstable over time, misfolding and aggregating in disease-causing amyloid deposits. This condition, called wild-type ATTR (ATTRwt) amyloidosis, primarily affects the heart. There is no known cure for ATTR amyloidosis, and currently available medications are limited to slowing the accumulation of misfolded TTR protein.

Nex-z, a CRISPR-Cas9 gene editing therapy, has the potential to become the first one-time treatment for transthyretin (ATTR) amyloidosis. It is designed to inactivate the TTR gene that encodes for the transthyretin (TTR) protein. Interim phase 1 clinical data showed the administration of nex-z led to consistent, deep and long-lasting TTR reduction. Intellia leads development and commercialization of nex-z as part of a multi-target discovery, development, and commercialization collaboration with Regeneron Pharmaceuticals.

Intellia CEO John Leonard said the data add to a growing body of evidence that a single dose of nex-z leads to “deep, durable, and consistent reductions in serum TTRs, with evidence of disease stability or clinically meaningful improvements in neuropathic impairment measures through two years.”

The global phase 1 trial is an ongoing open-label, multi-center, two-part study of NTLA-2001 in adults with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) or transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Part 1 of the ATTRv-PN arm of the study is an open-label, single-ascending dose escalation cohort and part 2 is an open-label, single-dose expansion cohort.

Across patients who received a one-time dose of 0.3 mg/kg or higher, the mean serum TTR reduction by Day 28 was 90 percent, with levels remaining virtually unchanged for at least 24 months.

The data showed favorable trends indicating stability or improvement in patients with ATTRv-PN, including six patients previously on patisiran, an RNAi therapy approved for hATTR. Stability or improvement was based on evaluation of multiple clinical and biomarker measures.

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. Observed liver enzyme abnormalities were not considered serious, were asymptomatic and resolved spontaneously without medical intervention or sequela.

“These data are also the first to show improvement in patients who had previously progressed on patisiran, further validating the hypothesis that increasingly deep reductions in TTR levels may lead to improved outcomes in ATTR amyloidosis,” said Intellia’s Leonard.

Photo: Intellia CEO John Leonard