Intellia shares fall after hospitalised CRISPR patient dies

Shares in gene-editing specialist Intellia Therapeutics came under renewed pressure today after a patient in one of its clinical trials who was hospitalised for liver toxicity died.

The company's stock was down almost 29% at the time of writing after the news emerged, having already slumped on last month's announcement that the phase 3 MAGNITUDE and MAGNITUDE-2 trials of nexiguran ziclumeran (nex-z) in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN) were being suspended. Shortly after, the FDA said it had placed the trials on clinical hold.

"We were deeply saddened to learn that the patient who experienced grade 4 liver transaminase elevations and increased total bilirubin following a dose of nex-z in the MAGNITUDE Phase 3 clinical trial […] passed away," said Intellia's president and chief executive, John Leonard, in the company's third-quarter business update.

He added that the company has been "advised by the treating physician that this is a case with complicating comorbidities, and it is being further evaluated."

In the meantime, Intellia – a specialist in CRISPR gene-editing co-founded by Nobel Prize winner Jennifer Doudna – is still waiting for an FDA clinical hold letter on the two nex-z trials, and Leonard said the firm is "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."

When the two trials were suspended, Intellia had enrolled more than 650 patients into MAGNITUDE and another 47 in MAGNITUDE-2, with grade 4 liver transaminase elevations seen in less than 1% of patients in the ATTR-CM trial and none of the subjects in the ATTR-PN study.

Nex-z is one of two late-stage projects on the go at Intellia, along with hereditary angioedema (HAE) candidate lonvoguran ziclumeran (lonvo-z), which completed enrolment in the phase 3 HAELO trial in September.

In its update, the company said it expects to report topline results from HAELO in the middle of 2026 and file for approval in the second half of the year, with a view to a commercial launch in the first-half of 2027.

The company ended the third quarter with a cash position of around $670 million, which it reckons will keep it operating through the launch of lonvo-z, assuming it gets regulatory approval.