Patient in Intellia CRISPR therapy trial dies

The patient who experienced serious raised liver enzymes in a phase 3 trial for Intellia Therapeutics’ in vivo CRISPR-based gene editing therapy — triggering a clinical hold — has passed away, the company reported.

The patient — revealed in an investor call to be a male in his early 80s with complicating comorbidities — experienced Grade 4 liver transaminase elevations and increased total bilirubin following a dose of nex-z in the MAGNITUDE transthyretin amyloidosis clinical trial, reported on October 27. He passed away on November 5.

“We have been advised by the treating physician that this is a case with complicating comorbidities, and it is being further evaluated. As we await the FDA’s clinical hold letter, we are working with clinical investigators and external experts to better understand the liver-related events that have been observed within MAGNITUDE and to develop our risk mitigation plan,” said Intellia president and CEO John Leonard, M.D.

During the investor call, Leonard said the company is adding safety protocols, for example, mandating that clinical sites collect additional labs from patients in the weeks following dosing to collect liver elevation sooner.

“We continue to believe in nex-z’s potential to address important unmet needs for patients with ATTR amyloidosis,” said Leonard.

Last week, the FDA verbally informed Intellia that it has placed a clinical hold on the investigational new drug applications for the MAGNITUDE and MAGNITUDE-2 phase 3 clinical trials for nex-z, but Intellia had already temporarily paused patient dosing and screening in the two trials for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN).

Hereditary ATTRv amyloidosis occurs when a person is born with mutations in the transthyretin (TTR) gene, which causes the liver to produce structurally abnormal 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. 

Based on Nobel Prize-winning CRISPR/Cas9 gene editing technology, nex-z is designed to inactivate the TTR gene that encodes for the TTR protein. 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.