Hereditary angioedema, a C1 inhibitor deficiency that is caused by an excess of plasma kallikrein. The genetic absence of prekallikrein (Fletcher syndrome) appears to be associated with normal health and life expectancy. Researchers therefore sought to assess safety and efficacy by evaluating NTLA-2002 (Intellia Therapeutics), an experimental CRISPR/Cas9-based therapy that targets KLKB1 – the gene that encodes the kallikrein protease – in hepatocytes. The goal of the therapy is to achieve lifelong control of HAE attacks with a single administration. This first-in-man Phase 1/2 study uses a single ascending dose design, testing doses of 25 mg, 50 mg and 75 mg, to assess the safety of the treatment and identify up to two doses to move into Phase 2 testing. The analysis included three patients treated with 25 mg of NTLA-2002. All three treated patients showed a clinically significant reduction in plasma kallikrein levels at week 32 (mean, 64%). The investigators noted that all three doses were generally well tolerated, with most adverse events being mild infusion-related reactions. In addition, there were no dose-limiting toxicities or clinically significant laboratory abnormalities.
