Intellia's gene editing therapies both post early successes as evidence grows for CRISPR potential

Intellia Therapeutics is closing out the week strong, reporting good news for a duo of gene editing trials. Both are early-stage, but the company is already prepping to move the transthyretin (ATTR) amyloidosis therapy, NTLA-2001, into what it hopes will be a pivotal study.

NTLA-2001, which has been licensed by Regeneron, already demonstrated earlier this year that it can significantly reduce a known biomarker of the disease for an extended period of time in ATTR amyloidosis patients with polyneuropathy. Now, data from the other arm of the study, of ATTR patients with cardiomyopathy, have shown a similar reduction.

Interim data showed reductions in the biomarker, called transthyretin, or TTR, of 93% and 92% at 0.7-mg/kg and 1.0-mg/kg doses, respectively, 28 days after the one-time intravenous treatment.

NTLA-2001 works by deploying lipid nanoparticles to the liver to drop off a two-part genome editing system. The first part is a guide RNA specific to the disease-causing gene, and the second part is a messenger RNA—the tech made famous by COVID-19 vaccines—to encode the Cas9 protein and carry out precision editing.

Intellia pointed to the latest data as further evidence that NTLA-2001 could become a one-time treatment to permanently inactivate the TTR gene and reduce the disease-causing protein in ATTR patients with cardiomyopathy. Based on the results, the companies have selected the 0.7-mg/kg dose to evaluate across both arms of the study, with enrollment set to complete by the end of the year.

"Together with the previously reported data from the polyneuropathy arm of this landmark study, these results strongly suggest that NTLA-2001 could serve as a single-dose treatment regardless of disease manifestation,” Intellia CEO John Leonard, M.D., said in the Sept. 16 release. “We look forward to completing the phase 1 study as we advance closer to a potential pivotal trial, which we expect will include patients in the U.S." 

ATTR amyloidosis is a rare and fatal disease that occurs in people born with TTR gene mutations, which cause the liver to produce abnormal, often misfolded TTR proteins. In the healthy form, TTR proteins help carry thyroid hormone and vitamin A in the blood. But the damaged proteins cause a host of problems in the nervous system, heart and other organs.

Intellia’s current studies are not geared to detect efficacy or patient benefit—that will come in more advanced testing later on—but TTR serum reduction is a known biomarker of the disease that signals a benefit. The actual benefits, such as relief from disease symptoms, will not be immediate after treatment with NTLA-2001, Leonard told Fierce Biotech back in February.

Regeneron secured the rights to commercialize NTLA-2001 as part of a $100 million licensing deal in 2020. Intellia has another CRISPR candidate, called NTLA-2002, which is in a phase 1/2 study for hereditary angioedema. Interim data from that trial also read out today, showing that a single dose led to a 65% and 92% mean plasma kallikrein reduction at 25-mg and 75-mg doses, respectively, at Week 8.