Intellia reports proof-of-concept data for redosing CRISPR-based therapy

Intellia Therapeutics (NTLA) presented new data demonstrating for the first time the potential for redosing with an investigational, in vivo CRISPR/Cas9 genome editing therapy. These data from the ongoing Phase 1 study of NTLA-2001, a single-dose treatment in development for transthyretin, or ATTR, amyloidosis, were presented at the Peripheral Nerve Society Annual Meeting, taking place June 22-25. NTLA-2001 is currently being evaluated in patients with either ATTR amyloidosis with cardiomyopathy, or ATTR-CM, or hereditary ATTR amyloidosis with polyneuropathy, or ATTRv-PN. Development and commercialization of NTLA-2001 is led by Intellia as part of a multi-target collaboration with Regeneron (REGN). Data from the Phase 1 trial has demonstrated that a one-time 55 mg dose of NTLA-2001 led to consistent, deep and durable reduction of serum TTR protein levels. This 55 mg dose was selected for further evaluation in the actively enrolling Phase 3 MAGNITUDE trial for ATTR-CM and the planned Phase 3 trial for ATTRv-PN. In the Phase 1 trial, the three initial patients enrolled in the dose-escalation portion received a 0.1 mg/kg dose of NTLA-2001, which led to a 52% median reduction in serum TTR by day 28. As expected, the 0.1 mg/kg dose resulted in lower-than-targeted serum TTR reduction. These patients were offered the opportunity to receive a follow-on dose of NTLA-2001 at the completion of the protocol-specified two years of observation. All three patients subsequently received a 55 mg dose, which led to the target pharmacodynamic effect and a 90% median reduction in serum TTR by day 28. The corresponding reduction from original baseline levels was a 95% median reduction in serum TTR. NTLA-2001 was generally well tolerated across all patients after receiving the follow-on dose. One of the three patients experienced a mild infusion-related reaction with the 55 mg dose. Safety and pharmacodynamics of the NTLA-2001 redosing were consistent with those observed after a single 55 mg dose. Further, favorable safety and tolerability continues to be observed, with patient follow-up beyond three years for the earliest dosed patient. “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,” said Intellia President and Chief Executive Officer John Leonard, M.D. “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.”