Intellia Can Re-dose Gene-Edited NTLA-2001, New Data Shows

Three patients who initially received a small dose of NTLA-2001 in a phase 1 dose escalation trial were offered a larger therapeutic dose after two years. Intellia Therapeutics does not typically need to re-administer its CRISPR gene-edited treatment for transthyretin (ATTR) amyloidosis. However, recent data indicates that re-dosing can be feasible.

Historically, gene therapies and gene editing treatments have been perceived as one-time interventions. The expectation is that a significant initial dose would be curative, negating the need for subsequent treatments. Intellia is now challenging this notion by demonstrating that re-dosing is indeed possible. This was evidenced when a group of patients from a phase 1 dose-escalation trial received a second, larger dose of NTLA-2001. Initially, these patients had been administered a dose that did not reach therapeutic levels. Intellia had committed to revisit these patients with a more substantial dose of NTLA-2001, and recent data presented at the Peripheral Nerve Society Annual Meeting in Montreal confirms this follow-up treatment.

NTLA-2001, developed in collaboration with Regeneron, is a gene-edited therapy designed for patients with ATTR amyloidosis, specifically those with cardiomyopathy (ATTR-CM) or hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). The therapy is already undergoing phase 3 trials, adhering to a single-dose treatment strategy.

John Leonard, M.D., CEO of Intellia, commented on the development: “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.” Leonard emphasized that the new data demonstrates the potential of re-dosing, a significant step that could pave the way for treating other diseases where multiple doses might be necessary to achieve the desired therapeutic effect.

The phase 1 trial had previously established that a one-time 55 mg dose of NTLA-2001 was effective in reducing serum TTR protein levels. This dose has progressed to advanced testing for ATTR-CM under the study named MAGNITUDE, which is currently enrolling participants. A separate trial for ATTRv-PN is also on the horizon.

Initially, three patients received a smaller 0.1 mg/kg dose of NTLA-2001, resulting in a 52% median reduction in serum TTR by day 28—this was anticipated to be below the therapeutic target. After two years of observation, these patients were offered a second dose, which they all accepted. Following the administration of the 55 mg dose, the patients exhibited a 90% median reduction in serum TTR by day 28. The re-dose was generally well tolerated; however, one patient experienced a mild infusion-related reaction. Other safety markers were consistent with those observed in patients who received the single 55 mg dose. The three patients will continue to be monitored for an additional three years.

These findings mark the first instance of clinical data showing that a gene editing therapy can be administered twice, providing a significant proof-of-concept for the potential flexibility and adaptability of such treatments.