Evidence supports redosing with an in vivo CRISPR-based therapy

CRISPR Cas9

Intellia Therapeutics has shared the first-ever clinical data demonstrating the potential for redosing with an investigational in vivo CRISPR-based therapy.

The data from the ongoing Phase I study of NTLA-2001, a single-dose treatment in development for transthyretin (ATTR) amyloidosis, were presented at the Peripheral Nerve Society Annual Meeting.

In the trial, follow-on dosing with a 55mg dose of NTLA-2001 led to a 90% median reduction in serum TTR at day 28 in the three patients who previously received the lowest dose in the Phase I dose-escalation study.

While redosing is not planned for the NTLA-2001 programme in transthyretin (ATTR) amyloidosis, a redosing option could be an important advantage of Intellia’s non-viral, lipid nanoparticle (LNP)-based delivery platform for future investigational therapies.

“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 enabled an additive pharmacodynamic effect on the target protein,” said Intellia President and Chief Executive Officer John Leonard. “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.”

Results of the Phase I trial

The three initial patients enrolled in the dose-escalation portion received a 0.1mg/kg dose of NTLA-2001, which led to a 52% median reduction in serum TTR by day 28. As expected, the 0.1mg/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 55mg 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 is currently being evaluated in patients with either ATTR amyloidosis with cardiomyopathy (ATTR-CM) or hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN).

Development and commercialisation of NTLA-2001 is led by Intellia as part of a multi-target collaboration with Regeneron.

Diana Spencer, Senior Digital Content Editor, DDW

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