Intellia Therapeutics and partner Regeneron’s in vivo CRISPR/Cas9 genome editing candidate, NTLA-2001, showed positive interim results in patients with transthyretin (ATTR) amyloidosis.
ATTR amyloidosis is a rare and fatal disease that occurs in people born with TTR gene mutations, which cause the liver to produce abnormal, misfolded TTR proteins. The damaged proteins, which in a healthy form help carry thyroid hormone and vitamin A in the blood, build up in the body, causing a host of problems to the nervous system, heart and other organs.
The study found that NTLA-2001 reduced serum levels of transthyretin, a key biomarker for the disease, by 87% in patients who received a higher dose. This result ousted the standard of care therapy which decreases transthyretin by 80%.
“It’s actually beyond what we expected, which is a wonderful thing,” said David Lebwohl, M.D Intellia’s chief medical officer. Lebwohl said that this is the first time gene editing has been proven to work in humans, which “opens up a whole new area of therapies for patients that wasn’t there.”
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.
CRISPR/Cas9 therapies work a lot like a vaccine but these treatments differ from gene therapies, some of which are already FDA-approved because they do not use a virus to deliver the gene-altering properties.
In this study, the gene editing therapy was delivered to the liver—which is the source of malformed transthyretin that builds up in the blood. Intellia is initially going after the polyneuropathy subtype of the disease, which shows up as nerve damage.
ATTR amyloidosis patients have few options, including Alnylam’s Onpattro, which brought in $306 million during 2020. Pfizer’s Vyndaqel is FDA-approved for the cardiomyopathy type of the disease and cleared to treat ATTR polyneuropathy in many countries. Intellia wants to target all forms of the disease, including wild type and in patients who are older. The polyneuropathy type affects “tens of thousands” of people around the world, while the more severe cardiomyopathy manifestation is in the hundreds of thousands, Lebwohl said.