CRISPR therapy cuts swelling attacks by 81%, Intellia study shows

The potential of a one-time CRISPR infusion is becoming increasingly promising. On Thursday, Intellia Therapeutics revealed that their investigational gene editing therapy has significantly reduced the frequency of dangerous and unpredictable swelling attacks associated with hereditary angioedema. This condition can result in severe or even life-threatening symptoms.

In a Phase 2 study involving 27 individuals, those who received the gene editing treatment experienced an approximate 80% decrease in the average rate of monthly attacks. Remarkably, eight out of eleven patients who were administered a mid-level dose have not experienced any swelling episodes during a median follow-up period of nine months since the infusion.

Dr. Danny Cohn from Amsterdam University Medical Center, who spearheaded the Phase 2 study, expressed his astonishment at the clinical outcomes. Speaking to Endpoints News, Cohn noted that all ten patients treated at his facility reported significant improvements. He highlighted the severe nature of the condition, noting that swelling can be disfiguring, extremely painful, or even fatal if it affects the upper airways. The therapy has been a transformative development for these patients.

The findings, published in the New England Journal of Medicine, offer the first comprehensive insights into a mid-stage study of a CRISPR therapy targeting the liver through an infusion of lipid nanoparticles. Intellia is currently recruiting for a larger Phase 3 study with 60 participants and plans to seek FDA approval by 2026. According to Intellia CEO John Leonard, this could become the first approved in vivo CRISPR drug if everything proceeds as expected.

Safety data from the CRISPR treatment appear encouraging, with headache, fatigue, and common colds reported as the most frequent side effects. However, the Phase 2 study’s approximately 80% reduction in attacks does not match the near-perfect results seen in a previous Phase 1 study, which showed a remarkable 98% reduction with a median follow-up of 20 months.

Cohn and Leonard suggested that the slightly lower response in the Phase 2 study might be due to patients being unaware if they received the CRISPR treatment or a placebo. Patients in the study are trained to recognize early signs of a potential swelling episode, which might include a cramp, itch, or tingling sensation, and to take medication immediately to prevent a full-blown attack. In the earlier study, where patients knew they were receiving the treatment, they might have been more inclined to wait before treating a potential attack.

Leonard emphasized the effectiveness of the drug, stating there is no doubt it works. The full relief from attacks reported by the group of eight patients was previously considered an unlikely outcome.

Hereditary angioedema is often caused by mutations in a gene for the enzyme C1 esterase inhibitor. Proper functioning of this enzyme is crucial for regulating kallikrein, a blood protein that triggers inflammation, swelling, and airway constriction. Intellia's therapy targets the gene responsible for kallikrein to prevent excessive swelling. At 16 weeks, the low dose reduced kallikrein levels in the blood by 55%, and the medium dose reduced the protein by 86%.

Dr. Cohn explained that rather than targeting the gene causing the disease, the therapy rebalances the system by decreasing plasma kallikrein. If the drug succeeds in its next clinical trial, it will face competition from other treatments, such as Takeda’s antibody Takhzyro, which also targets kallikrein, and Ionis’s gene-silencing antisense oligonucleotide, which similarly reduced swelling attacks by 81% when taken every four weeks in a Phase 3 study. Ionis announced in August that it was preparing to submit its drug for regulatory approval.

Leonard is confident that Intellia’s one-time treatment will be a compelling option for patients, believing that people will quickly recognize its potential and be highly enthusiastic.