Lessons from the first-in-human in vivo CRISPR/Cas9 editing of the TTR gene by NTLA-2001 trial in patients with transthyretin amyloidosis with cardiomyopathy

Abstract

Study and results: The first-in-human in vivo CRISPR/Cas9 trial of TTR Gene editing by NTLA-2001 in patients with Transthyretin Amyloidosis and cardiomyopathy was designed to evaluate the safety, tolerability, efficacy, and pharmacokinetic and pharmacodynamic responses to IV NTLA-2001 administration and its effect on serum transthyretin (TTR) levels in patients with ATTR amyloidosis and cardiomyopathy.  Twelve subjects received NTLA-2001 (three NYHA I/II subjects at 0.7 mg/kg, three subjects at 1.0 mg/kg, and six NYHA III subjects at 0.7 mg/kg). Serum TTR levels were reduced from the baseline in all subjects (mean>90% after 28 days). Mean % reductions (+/-SEM) from baseline to day 28 were: NYHA I/II at 0.7 mg/kg = 92% (1%), at 1.0 mg/kg = 92% (2%), and for NYHA III at 0.7 mg/kg = 94% (1%) maintained through 4-6 months. Two of the 12 patients (16.7 %) reported a transient infusion reaction. One patient experienced a grade 3 infusion-related reaction that resolved without any clinical sequelae.