Intellia Successfully Redoses CRISPR Gene Editing Therapy


Three participants with ATTR amyloidosis have received follow-on doses of NTLA-2001 with no serious complications for up to 3 years of follow-up.

Intellia Therapeutics’ CRISPR editing therapy NTLA-2001 has demonstrated the ability to safely be redosed, according to new data from a phase 1 trial (NCT04601051) evaluating the therapy in patients with transthyretin (ATTR) amyloidosis.1

Follow-on data from patients that received a supplemental dose of NTLA-2001 were presented at the 2024 Peripheral Nerve Society (PNS) Annual Meeting, held June 22-25, in Montreal, Canada, by Jorg Taubel, MD, FFPM, FESC, chief executive officer and founder, Richmond Pharmacology.1

“Today’s data showcase an exciting new platform advancement for Intellia and the field of gene editing. For the first time ever, we demonstrated that redosing with CRISPR, utilizing our proprietary, non-viral LNP-based delivery platform, enabled an additive pharmacodynamic effect on the target protein,” John Leonard, MD, President and Chief Executive Officer, Intellia, said in a statement.2

The follow-on data were from the 3 initial patients enrolled in the dose-escalation portion of the phase 1 trial. The patients received 0.1 mg/kg of NTLA-2001, which led to an expected, lower-than-targeted 52% median reduction in serum TTR by day 28. These patients then opted to receive a 55 mg dose after 2 years of observation as according to study protocol. This dose led to the target pharmacodynamic effect and a 90% median reduction in serum TTR by day 28, representing a 95% median reduction from original baseline levels.1

WATCH NOW: Ahmad Masri, MD, MS, on the Potential of Gene Therapy in ATTR Amyloidosis

One patient experienced a mild infusion-related reaction after the follow-on dose, but the second infusion was generally well tolerated across these 3 participants with a safety profile similar to those who received a single, 55 mg dose, for up to 3 years of follow-up for the earliest dosed patient.1

“While redosing is not planned for the NTLA-2001 program for the treatment of transthyretin amyloidosis, part of our commitment to patients enrolled in the dose-escalation portion of the Phase 1 study was to provide them with the opportunity to receive the therapeutic dose selected if they did not reach the target protein reduction level. These data provide platform proof-of-concept that we can re-dose, if necessary, enabling us to pursue treatment of other diseases where patients might need more than one dose to reach the desired therapeutic effect,” Leonard added.2

NTLA-2001 is a CRISPR/Cas9 gene editing therapy delivered via a lipid nanoparticle nonviral system designed to inactivate the TTR gene that encodes for the TTR protein. In patients with ATTR amyloidosis, the liver produces structurally abnormal, misfolding TTR that builds up as amyloid in the body, causing serious complications in the heart, nerves, digestive system, and other tissue.

It is currently being evaluated in patients with either ATTR amyloidosis with cardiomyopathy or hereditary ATTR amyloidosis with polyneuropathy in the phase 1 trial and is being developed jointly between Intellia and Regeneron. Following promising phase 1 data demonstrating long-lasting TTR reductions, the phase 3 MAGNITUDE trial (NCT06128629) is currently enrolling participants to receive the selected 55 mg dose.

1. Taubel J, Gane E, Fontana M, et al. Activity Of Follow-on Dosing ForAn Investigational In Vivo CRISPR-Based LNP Therapy In Transthyretin Amyloidosis. Presented at: 2024 PNS Annual Meeting, June 22-25; Montreal, Canada. Poster #O435
2. Intellia Announces Positive Clinical Proof-of-Concept Data for Redosing a CRISPR-Based Therapy with its Proprietary LNP-Based Delivery Platform. News release. Intellia Therapeutics. June 25, 2024.
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