Intellia's CRISPR drug could offer one-shot HAE treatment

A single dose of a gene-editing drug being developed by Intellia Therapeutics almost eliminated attacks in patients with hereditary angioedema (HAE) in a clinical trial, pointing to the potential of CRISPR-based drugs delivered in vivo to treat diseases.

The results of the phase 1 study of NTLA-2002 – which inactivates the gene encoding kallikrein B1 (KLKB1) – have been published in the New England Journal of Medicine, revealing that it led to 95% average reduction in monthly HAE attack rate, with nine out of 10 patients completely attack-free after at least 16 weeks of follow-up, even if they stopped taking preventative therapies.

Currently, patients have to have lifelong treatment with C1 esterase, bradykinin B2 receptor, or plasma kallikrein inhibitor drugs as prophylaxis against attacks.

While still early, the results back up the potential of NTLA-2002 to provide “lifelong control of angioedema attacks after a single dose,” according to the trial investigators. The subjects in the study will be followed for up to 15 years in order to gauge the durability of the treatment.

HAE is a rare genetic disorder estimated to affect about one in 10,000 to one in 50,000 people worldwide. It can result in unpredictable and potentially life-threatening recurring attacks of debilitating and painful swelling in various parts of the body, which can last for several days and lead to asphyxiation if affecting the airways.

The trial result comes shortly after the first-ever CRISPR-based therapy was approved for market - Vertex Pharma and CRISPR Therapeutics’ Casgevy (exagamglogene autotemcel) for sickle cell disease beta thalassaemia – although, that is an ex vivo application of the gene-editing technology, as it involves editing of bone marrow cells outside the body, rather than systemic dosing of the CRISPR agent.

“Despite currently available treatments, people living with hereditary angioedema continue to face frequent anxiety about their next swelling attack,” commented Intellia’s president and chief executive, John Leonard. “We are highly encouraged by [this] data and look forward to presenting extended follow-up from the phase 1 and results from the phase 2 portion [of the trial] later this year.”

Intellia is also planning to move NTLA-2002 quickly into a pivotal clinical trial programme, targeting a start before the end of the year if it can get regulatory approvals for the study.

The company – co-founded by Nobel Prize winner Jennifer Doudna – was the first to generate clinical data with an in vivo CRISPR drug back in 2021 with NTLA-2001, a Regeneron-partnered drug now in late-stage clinical testing for rare disease ATTR amyloidosis.