Intellia doesn't need to re-dose gene edited NTLA-2001. But new data shows it can be done

Intellia Therapeutics doesn’t need to re-dose patients with a CRISPR gene edited therapy for transthyretin (ATTR) amyloidosis. But new data suggests it could be done.

Gene therapies and gene editing medicines have long been thought to be a one-and-done situation, where patients receive a large upfront dose and then cannot be re-dosed again. The hope is that they are curative with the single dose.

But now Intellia has shown that re-dosing is possible after a group of patients who participated in a phase 1 dose-escalation trial were given another, larger, dose. The patients previously received a dose that did not reach a therapeutic level and Intellia had promised to circle back to them later with more of NTLA-2001. The CRISPR company presented the new re-dosing evidence at the Peripheral Nerve Society Annual Meeting in Montreal on Tuesday.

The Regeneron-partnered gene-edited therapy is being developed for patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM) or hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). Already in phase 3 testing, the drug is advancing with the single-dose strategy.

“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,” said Intellia CEO John Leonard, M.D.

“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.”

The phase 1 trial previously showed that a one-time 55 mg dose of NTLA-2001 reduced serum TTR protein levels. This dose moved on to the late-stage test for ATTR-CM called MAGNITUDE, which is actively enrolling. Another trial for ATTRv-PN is planned.

Three initial patients who received the smaller 0.1 mg/kg dose of NTLA-2001 had a 52% median reduction in serum TTR by day 28, which was lower than target—as expected. After completing two years of observation, the patients were offered a follow-up dose, which was accepted by all three.

Once they received the 55 mg dose, the patients experienced 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 patients who received the single 55 mg dose. Observation of the trio of patients will continue for three years.

Intellia said these results are the first clinical data showing that a gene editing therapy can be administered twice.