Crispr gene editing treatment from Intellia succeeds in Phase 3 trial

Intellia Therapeutics The Crispr-based treatment for a rare swelling condition met its goals in a late-stage trial, a breakthrough in the field of gene editing and putting the company on the path to approval from the U.S. Food and Drug Administration, the company said.

The company’s therapeutic uses Nobel Prize-winning technology By editing DNA, Crispr turns off the gene that controls the production of a peptide that is overactive in people with hereditary angioedema, causing them to experience potentially life-threatening episodes of swelling. Intellia’s treatment is administered through an hour-long infusion and adjustments are made directly in the liver.

Intellia said the one-time treatment reduced attacks by 87% compared to placebo, meeting the main goal of the study. Six months after treatment, 62 percent of patients were free of attacks and did not use other treatments, Intellia said.

The company described the safety and tolerability of the treatment as “positive” and reported that the most common side effects were infusion-related reactions, headaches, and fatigue. Analysts were closely monitoring the safety of the trial because a patient in a separate trial using a different treatment from Intellia had died. According to the company, this patient developed liver damage and eventually died from septic shock following an ulcer.

“When you think about where we started with Crispr just 12 years ago with some basic knowledge, I think there’s been a lot of talk about what might be possible, and we’ve had reports along the way in terms of milestones, but this is the first Phase 3 data in any indication that you’re actually altering a disease-causing gene with Crispr in vivo,” said Intellia CEO John Leonard.

The only FDA-approved Crispr-based drug comes from Vertex Pharmaceuticals. Gene editing, called Casgevy, is done outside the body or ex vivo. The process requires collecting a person’s blood cells, making adjustments outside the body, and then giving them back to the patient. Intellia’s treatment, meanwhile, makes the adjustments inside the body or in vivo.

Intellia said it has begun an ongoing application with the FDA and plans to complete the application in the second half of this year. If approved, the company plans to launch the treatment in the United States in the first half of next year.

If approved, Intellia’s treatment, lonvoguran ziclumeran, would compete with nearly a dozen other chronic drugs for HAE. Despite the appeal of a one-time treatment, genetic drugs have not always been a commercial success. BioMarin, for example, withdrew its gene therapy for Hemophilia A due to poor sales.

Leonard said there are important differences between the two, such as BioMarin’s therapy facing questions about how long the effects last. In contrast, he said, in almost six years of Intellia, there has not been a single case where the effects diminished over time.

Despite the results, he is reluctant to call Intellia’s treatment a functional cure.

“I think this is a turning point for the disease and a turning point for Crispr-based in vivo therapy where you can make changes. [and] “And as far as we can tell, we don’t have a single patient in this program or any other program where there’s any reduction in the impact of what we’re doing or what we’re seeing regarding the clinical aspects of the disease.” So it’s pretty exciting.”

Clarification: This story has been updated to clarify that a patient in a separate trial of a different treatment from Intellia developed acute liver injury and ultimately died of septic shock following an ulcer.