The promise of a one-and-done CRISPR infusion is beginning to look more real than ever.
On Thursday, Intellia Therapeutics announced that an experimental gene editing therapy reduced dangerous and unpredictable swelling attacks caused by the disease hereditary angioedema.
Hereditary angioedema can cause disfiguring or even fatal symptoms. But in the 27-person, Phase 2 study, patients who received the gene editing treatment saw the mean rate of monthly attacks fall by about 80%. And eight of 11 patients who got the mid-level dose of the drug have had zero attacks during a median follow-up of nine months since the infusion.
“I was overwhelmed by the clinical response,” Danny Cohn, a doctor at Amsterdam University Medical Center who led the Phase 2 study, told Endpoints News in an interview. Cohn said the 10 patients treated at his hospital have all reported dramatic improvements.
“These swellings can be disfiguring when the face is swollen, extremely painful when the intestines are swollen, or even fatal when the upper airways are involved,” he said. “So this has really been a game-changer.”
The results, published in the New England Journal of Medicine, provide the first detailed look at a mid-stage study of a CRISPR therapy delivered to the liver using an infusion of lipid nanoparticles. Intellia is already recruiting for a larger 60-person Phase 3 study and aims to file for FDA approval in 2026.
“Unless something changes, this will be the first in vivo CRISPR drug that’s approved,” Intellia CEO John Leonard told Endpoints News.
So far, the CRISPR treatment seems safe. Intellia said that headache, fatigue and a common cold were the most frequent side effects.
While the data are impressive, the roughly 80% reduction in attacks doesn’t look quite as high as the near-perfect results from a Phase 1 study which showed a remarkable 98% reduction through the latest data cutoff, with patients followed a median of 20 months.
Intellia’s stock was down about 17% on Thursday morning.
Cohn and Leonard both told Endpoints separately that they believe the lower response in the new Phase 2 study is likely due to patients not knowing if they got the CRISPR treatment or the placebo.
Patients are taught to report signs of a potential swelling episode — which might manifest as a cramp, an itch, or a tingling sensation — and immediately take a drug to prevent a full-blown attack. In the earlier study, where everyone knew they got the treatment, patients may have been more likely to hold off on treating a potential attack.
“What’s clear is the drug actively works. I mean, there’s no doubt about that,” Leonard said.
Full relief from attacks, as the group of eight patients experienced, is not a result for patients that has been thought possible before, he said.
Most people with hereditary angioedema have mutations in a gene for an enzyme called C1 esterase inhibitor. Proper functioning of that enzyme is needed to control another blood protein called kallikrein that kick-starts a process that causes inflammation, swelling and constriction of airways.
Intellia’s therapy breaks the gene for kallikrein to prevent runaway swelling. The low dose reduced kallikrein levels in the blood by 55% and the medium dose reduced the protein by 86% at 16 weeks.
“We are not targeting the gene that is causing the disease,” Cohn said. “But we are rebalancing the system by decreasing plasma kallikrein.”
If the drug passes its next clinical trial, it will face competition from other therapies. Takeda’s commercial antibody Takhzyro also targets kallikrein. And Ionis is developing its own genetic medicine for the disease, a gene-silencing antisense oligonucleotide that reduced swelling attacks by 81% when taken every four weeks in a Phase 3 study. Ionis said in August that it was preparing to submit the drug to regulators.
Leonard believes that Intellia’s one-and-done treatment will be an attractive alternative. “We think very quickly people will understand what’s possible and be very enthusiastic,” he said.
Editor’s note: This story was updated with information on Intellia’s stock.