An international team of researchers from eight countries has presented Phase III clinical trial results for lonvoguran ziclumeran (NTLA-2002) – the first in-vivo CRISPR therapy for hereditary angioedema, a rare and life-threatening condition characterised by recurrent swelling attacks. A single intravenous dose of the drug, developed by Intellia Therapeutics, durably reduced attack rates without serious side effects. The findings open the door to a fundamentally new approach to treating the disease.
Hereditary angioedema is caused by mutations in the SERPING1 or F12 genes, leading to uncontrolled release of kallikrein and kinins. This results in attacks of severe swelling of the limbs, face, larynx and abdominal organs. Such episodes can be fatal due to suffocation or acute abdomen and require intensive care, but existing drugs are not always sufficiently effective and are not available in all countries.
The double-blind, randomised, placebo-controlled HAELO trial enrolled 80 patients aged 16 and older with confirmed diagnosis. Participants received either a single infusion of the drug or placebo. Lonvoguran ziclumeran consists of lipid nanoparticles carrying CRISPR-Cas9 components that knock out the KLKB1 gene, which encodes the kallikrein precursor.
The drug reduced attack rates by 87% (0.26 vs. 2.10 per month in the placebo group). The effect was seen from week four and persisted throughout the follow‑up period (average 7.5 months). Complete freedom from attacks was achieved in 62% of patients versus 11% in the control group. Quality of life improved more markedly than with placebo (27.64 vs. 6.47 points).
Adverse events were reported in 92% of participants in the active group and 86% in the control group. Infusion‑related reactions were significantly more common in the lonvoguran ziclumeran group (62% vs. 18%). No severe or serious adverse events were recorded. The researchers stressed that a single administration provides a durable effect, but long‑term follow‑up of participants is ongoing.
Earlier it was reported that US researchers at Beth Israel Deaconess Medical Center in Boston had modified the CRISPR tool to target the extra chromosome 21 that causes Down syndrome. According to their data, the new technique increased the efficiency of integrating the XIST silencing gene into the target chromosome from 20% to 40%. This opens prospects for developing the first molecularly targeted therapy for the condition.
