Lonvoguran Ziclumeran - In Vivo CRISPR Gene Editing in Hereditary Angioedema.
Danny M Cohn, Padmalal Gurugama, Hilary J Longhurst et al.
✦ AI-curated · Sources linked
In 30 seconds
This phase 3, multicenter, double-blind randomized trial evaluated a single intravenous infusion of lonvoguran ziclumeran, an investigational in vivo CRISPR gene-editing treatment, in patients aged 16 years or older with hereditary angioedema and C1 inhibitor deficiency. Among 80 randomized patients, the least-squares mean monthly attack rate from weeks 5 through 28 was 0.26 with lonvo-z and 2.10 with placebo, a relative difference of -87% (95% CI, -93 to -78; P<0.001). No serious or grade 3 or higher adverse events were reported in the lonvo-z group during the reported follow-up.
Key findings
- The monthly attack rate was 0.26 with lonvo-z versus 2.10 with placebo from weeks 5 through 28.
- The relative difference in monthly attack rate was -87% (95% CI, -93 to -78; P<0.001).
- Adverse events were reported in 92% of lonvo-z recipients and 86% of placebo recipients through week 28.
- No serious or grade 3 or higher adverse events were reported in the lonvo-z group.
Why it matters
Hereditary angioedema can cause recurrent, debilitating and potentially life-threatening attacks. The marked reduction in attacks after one infusion suggests that in vivo gene editing may offer a substantially different treatment approach for this population. The trial also provides controlled evidence on short-term safety, although longer follow-up will be important for assessing the durability and safety of a gene-editing intervention.
What to keep in mind
Follow-up was limited: median duration was 7.5 months (range, 4.9 to 12.8), and the primary attack-rate assessment covered weeks 5 through 28.