Intellia Therapeutics has revealed that a single infusion of its experimental CRISPR therapy, called NTLA-2002, almost entirely eliminated swelling attacks in 10 people with hereditary angioedema. People with the genetic condition experience sudden inflammation that can cause disfiguring, painful and sometimes deadly swelling throughout the body.
The new data from the Phase 1 trial follow a preliminary readout from last summer based on the first 16 weeks of observations in the study. In the new readout, which showed that the therapy continued to work after an average of 20 months, swelling attacks diminished by 98% in the 10-person group.
One individual has remained attack-free for more than 26 months, and two people suffering frequent swelling attacks, 14 and 17 times a month, also remained attack-free after the initial phase of the trial.
“Cure” is a word that many drug developers shy away from. But the implicit promise of one-time genetic therapies is that they can address the root cause of diseases and, hopefully, end them.
“These long-term data provide strong evidence that NTLA-2002 could be a one-time, potential functional cure for this debilitating and life-threatening disease,” CEO John Leonard said in a press release. The data were presented Sunday at the European Academy of Allergy and Clinical Immunology in Valencia, Spain.
Ionis Pharmaceuticals, a company developing a different type of genetic medicine called an antisense oligonucleotide, also announced data from two Phase 3 studies at the conference. Hereditary angioedema patients treated with its drug donidalorsen every four weeks had 81% fewer attacks, and patients treated every eight weeks had 55% fewer attacks. The company plans to file an application this year for approval of the drug.
An Intellia spokesperson told Endpoints News that topline data from its follow-up Phase 2 study are expected within months. The company is also in talks with regulators to begin a pivotal Phase 3 study in the second half of the year. With fewer than 75 patients in that trial, Intellia expects to move fast, and if all goes well, it plans to submit the therapy for FDA approval in 2026.
If that timeline holds, the hereditary angioedema treatment could leapfrog Intellia’s more advanced program for a liver, nerve and heart disease called transthyretin amyloidosis. It could also become the first in vivo CRISPR therapy, infused directly into the body, approved in the US.
The treatment works by making a small change to DNA that prevents the liver from making an enzyme called kallikrein, which can cause leaky blood vessels and swelling in people with the disease. Kallikrein blood levels remained reduced by 60%, 88% and 95% in the low, medium and high-dose groups, respectively, suggesting that the edits remained stable since the preliminary results last year.
Intellia said the most common side effects were infusion-related reactions and fatigue, and did not report any longer-term safety issues from the treatment.