At the American Heart Association (AHA) Scientific Sessions held on November 5–7 in Chicago, Illinois, US, Intellia presented updated interim data from the cardiomyopathy arm of its ongoing Phase I trial of NTLA-2001, a clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing therapy, for the treatment of transthyretin (ATTR) amyloidosis. Among 12 patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM), a single intravenous infusion of NTLA-2001 led to deep and durable responses, fueling excitement for the prospect of a first systemically administered in vivo CRISPR therapy.

ATTR amyloidosis is a rare, progressive, and ultimately fatal disease in which the transport protein transthyretin (TTR) becomes misfolded as a consequence of genetic mutations or ageing. This leads to the extracellular deposition of TTR fibrils in the body’s tissues, such as the heart (ATTR-CM), which can lead to heart failure, or the nerves (ATTR-polyneuropathy [PN]), which can lead to nerve damage.

NTLA-2001, which Intellia is developing in collaboration with Regeneron, exerts its effects by editing the TTR gene in hepatocytes. It consists of a proprietary lipid nanoparticle delivery system with liver tropism. The system carries a single guide RNA (sgRNA), which targets TTR, and a human-codon-optimised messenger RNA (mRNA) sequence of Streptococcus pyogenes Cas9 protein, which carries out the precision editing. This decreases the production of disease-causing TTR.

The therapy previously made waves in the gene editing field in June 2021 with the release of positive interim data for the neuropathy arm of the trial. Although this data only provided analyses over a 28-day period, the publication of the first clinical data supporting the safety and efficacy of an in vivo CRISPR therapy was hailed as a watershed moment in genomics, culminating in soaring stock shares for Intellia. However, the latest data, which was obtained from the cardiomyopathy arm of the study, shows that NTLA-2001 induces sustained reductions in serum TTR, with patient follow-up ranging from four to six months. Critically, the durability of this response provides credence to Intellia’s objective of permanently inactivating the TTR gene, potentially curing the disease.

The new data is also certain to generate excitement beyond the ATTR amyloidosis field as the technology could be applied to treat a wide range of genetic diseases. For example, Intellia is already investigating CRISPR-based therapies in treating diseases such as hereditary angioedema, alpha-1 antitrypsin deficiency, haemophilia A, and haemophilia B.

Additionally, with CRISPR therapies gaining momentum over recent years, investment in the technology is at an all-time high. GlobalData notes that while 74 venture capital deals for companies developing CRISPR-based therapies took place during 2012–2021, 42% of these occurred in the last two years. Although investments in CRISPR-based therapies can certainly be regarded as high-risk due to the lack of long-term safety and efficacy data, the potential of these therapies to cure diseases that have previously been very difficult to treat will ensure they continue to attract strong investment in the years to come.