Clinical safety and tolerability of in vivo gene editing drug ART001 for ATTR amyloidosis.

BACKGROUND

ATTR amyloidosis is a disease caused by abnormal deposition of TTR (transthyretin) protein in tissues. ART001 is an in vivo gene therapy drug using lipid nanoparticle (LNP) to deliver mRNA encoding SpCas9 (Streptococcus pyogenes Cas9) and a single guide RNA (sgRNA) for knocking-out of the TTR gene in hepatocytes and reducing serum TTR levels.

METHODS

In an investigator-initiated trial (IIT) of ART001 for 10 ATTR Amyloidosis patients, each patient was given one dose of ART001 which ranged from 0.05 mg/kg to 1.0 mg/kg. The aim was to evaluate ART001's safety, side effects, PK, PD, and efficacy based on circulating TTR protein levels.

RESULTS

At 0.7 mg/kg in 3 subjects and 1 mg/kg in 3 subjects, TTR protein reductions averaged 84 and 92% at 72 weeks. No infusion-related reactions (IRRs), serious adverse events (SAEs) or serious adverse reactions (SARs) were observed.

CONCLUSION

A single injection of ART001 achieved > 80% TTR knock-down at doses > 0.5 mg/kg and lasted for at least 72 weeks without IRRs, SARs or SAEs. ART001 has the potential to be a safe, effective and permanent therapeutic option for ATTR Amyloidosis patients. (Funded by Accuredit Therapeutics).

CLINICAL TRIAL REGISTRATION: Trial registration: ChiCTR, ChiCTR2400081216. Registered 26th Feb, 2024 - retrospectively registered, https://www.chictr.org.cn/showprojEN.html?proj=210566.