The FDA cleared Intellia Therapeutics to run a Phase III study of its CRISPR-based therapy for transthyretin (ATTR) amyloidosis with cardiomyopathy, paving the way for the first pivotal study of an in vivo gene editing treatment in the US.
The gene editing company said Wednesday it expects to start the Phase III study by the end of the year. The biotech, co-founded by Nobel laureate Jennifer Doudna, has yet to run a study in the US. Intellia enrolled all 72 patients in its early-stage trial of the ATTR amyloidosis treatment in the UK, France, New Zealand and Sweden, according to the federal clinical trials database.
Intellia CEO John Leonard confirmed to Endpoints News to expect the Phase III trial to be similar to the one for Amvuttra, an RNA treatment developed by Alnylam for the same disease. That study, which enrolled 655 patients across the globe, is measuring events such as death and hospitalization from heart failure in patients who receive treatment versus placebo as its primary endpoint.
“The US will produce — based on our expectations and interactions with investigators and patient groups — the lion’s share of the patients,” Leonard said.
He added that the company has sites with patients waiting already to get into the trial and declined to comment further on the Phase III study, noting the company plans to share further details during a November investor call.
Intellia’s ATTR amyloidosis treatment, known as NTLA-2001, is meant to be a one-time treatment for the disease in which misfolded protein clumps build up in the body. When the proteins accumulate in the heart, they lead to symptoms similar to heart failure such as swelling, trouble breathing, and arrhythmias. Gene editors are delivered via an infusion to the patient and go to the liver, where they knock out the gene responsible for making transthyretin and lower levels of the protein.
Wednesday’s announcement is a major regulatory step for the gene editing space. The FDA has taken a more cautious approach than authorities in other regions in how it regulates studies of treatments that edit patients’ DNA directly in their bodies. In response, Intellia and another gene editing company, Verve Therapeutics, have run their early-stage studies outside the US.
In March, the FDA cleared Intellia to study its other gene editing treatment for hereditary angioedema — a genetic disease that causes severe swelling episodes — in people in the US, but asked for additional information about the treatment’s effect on the reproductive system before Intellia tested it in women of child-bearing age. Intellia then decided to finish enrolling the Phase II portion of the study at sites in Europe and New Zealand.
The CRISPR-based treatment lowered levels of transthyretin protein in the blood by over 90% one month after treatment, according to a 12-patient snapshot of the Phase I study Intellia presented last year. The company is also testing the treatment in another manifestation of the disease which affects a person’s nerves and plans to share more data from the early-stage study before the end of this year.
Intellia is partnered with Regeneron on the program, and the duo recently expanded their in vivo gene editing pact to neurological and muscular diseases.
For its gene editing programs that are still in preclinical testing, Leonard said that the company will decide where to run early-stage studies — whether in the US or elsewhere — on a “case-by-case basis.”
“When we began a few years ago, there was a lot less known,” Leonard said. “The feedback we had gotten in terms of information that was requested had a great deal of overlap from the different regulatory agencies. It was the case that certainly from a clinical program perspective, the FDA wanted a different cadence from what we saw, almost uniformly with other regulatory agencies outside the United States.”
Intellia’s stock $NTLA fell 3% Wednesday morning.
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