Intellia Therapeutics announced positive phase 2 data from an ongoing study of its investigational in vivo CRISPR-based gene editing therapy, NTLA-2002, in patients with hereditary angioedema (HAE) — with results indicating that the therapy has the potential to eliminate HAE attacks following a one-time infusion.
HAE is a rare, genetic disease that leads to severe, recurring and unpredictable inflammatory attacks in various organs and tissues of the body, which can be painful, debilitating and life-threatening. Currently approved HAE therapies require chronic, burdensome administration and while they reduce these angioedema attacks, they don’t eliminate them. NTLA-2002 is designed to prevent HAE attacks by inactivating the kallikrein B1 (KLKB1) gene, which encodes for prekallikrein, the kallikrein precursor protein.
In the phase 2 study, which included a total of 27 participants randomized to receive one of two single doses of NTLA-2002 (25 mg or 50 mg) or placebo, deep attack rate reductions were achieved in both dose levels tested. According to Intellia, the single 50 mg dose resulted in a mean monthly attack rate reduction of 77% and 81% compared to placebo during weeks 1-16 and 5-16, respectively.
Even more impressive, eight of 11 patients in the 50 mg arm were completely attack free following a one-time infusion through the latest follow-up — supporting NTLA-2002’s potential to be a functional cure for HAE.
The therapy appears to be well tolerated at both dose levels with the most frequent adverse events being headache, fatigue and common cold. The only serious AE came from the placebo arm, where a patient experienced tongue swelling with breathing impairment that was attributed to their underlying HAE.
Results were published in the New England Journal of Medicine and will be presented at the 2024 American College of Allergy, Asthma & Immunology (ACAAI) Scientific Meeting on Saturday, October 26.