Intellia shares early data for CRISPR-based ATTR amyloidosis therapy

Intellia Therapeutics announced positive new clinical data from an ongoing phase 1 trial of its investigational in vivo CRISPR-based gene editing therapy in patients with transthyretin (ATTR) amyloidosis, a rare and fatal protein disorder.

According to Intellia, hereditary 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. 

The phase 1 trial is an open-label, two-part study evaluating the safety and activity of nexiguran ziclumeran (nex-z) in patients with either ATTR amyloidosis with cardiomyopathy (ATTR-CM) or hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). The new data, according to Intellia, offers compelling evidence that the deep and persistently low levels of TTR reduction achieved with nex-z may favorably impact disease progression for people living with ATTR amyloidosis.

Across all 36 trial patients, a single dose of nex-z led to consistently rapid, deep and sustained serum TTR reduction, regardless of baseline levels, through the latest follow-up. At month 12, the mean serum TTR reduction was 90%, and the mean absolute residual serum TTR concentration was 17 µg/mL. The 11 patients who have reached 24 months of follow-up have continued to show a sustained response with no evidence of a waning effect over time. 

Intellia says the results have increased its confidence in the success of the company’s active phase 3 studies, which are also based on the hypothesis that greater TTR reduction may lead to greater clinical benefit.

Development and commercialization of the one-time treatment is led by Intellia as part of a multi-target collaboration inked with Regeneron back in 2016. Per the deal, Regeneron paid Intellia $75 million upfront for the exclusive rights to discover and develop CRISPR-based products against up to 10 targets.