Intellia Therapeutics and Regeneron Pharmaceuticals have reported positive interim results from the Phase I clinical trial of their CRISPR therapy candidate, NTLA-2001, to treat transthyretin (ATTR) amyloidosis.

Conducted by Intellia, the ongoing trial involves adults with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) in the UK and New Zealand.

NTLA-2001 is a CRISPR/Cas9-based therapy designed for intravenous administration.

The candidate is intended to inactivate the TTR gene in liver cells to stop the creation of misfolded transthyretin protein, which builds up in body tissues and leads to ATTR amyloidosis complications.

A single 0.1mg/kg or 0.3mg/kg dose of NTLA-2001 is being assessed in the open-label, multi-centre, two-part Phase I trial for safety, tolerability, pharmacokinetics and pharmacodynamics.

The trial will enrol up to 38 subjects.

The interim results were gathered from the first six ATTRv-PN patients across two single-ascending dose arms. Decrease in levels of serum TTR, which causes the disease, were measured from baseline to day 28.

Data revealed dose-dependent serum TTR reductions with NTLA-2001 treatment. A mean decrease of 52% was seen in the three patients in the 0.1mg/kg dose arm.

Among the three patients on 0.3mg/kg dose, the mean decrease was 87% by day 28, including a 96% reduction in one patient.

The company noted that the standard of care for ATTRv-PN usually leads to about 80% TTR reductions.

NTLA-2001 was generally well-tolerated at the tested dose levels, without any serious adverse events or liver findings by day 28.

Intellia Therapeutics president and CEO John Leonard said: “These are the first ever clinical data suggesting that we can precisely edit target cells within the body to treat genetic disease with a single intravenous infusion of CRISPR.

“The interim results support our belief that NTLA-2001 has the potential to halt and reverse the devastating complications of ATTR amyloidosis with a single dose.”

The single-dose expansion cohort of the Phase I trial will be commenced later this year after determining a recommended dose in the dose-escalation part.

Upon completion of the Phase I trial, Intellia intends to conduct pivotal studies for polyneuropathy and cardiomyopathy manifestations in ATTR amyloidosis patients.