Intellia Therapeutics, building exterior and company sign, Cambridge, Massachusetts, USA.
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Intellia Therapeutic said its Crispr-based treatment for a rare swelling disease met its goals in a late-stage trial, marking a milestone in the field of gene editing and putting the company on track to seek approval from the U.S. Food and Drug Administration.
The company’s treatment uses Nobel Prize-winning Crispr technology to edit DNA and turn off the gene that controls the production of an overactive peptide in people with hereditary angioedema, causing life-threatening bouts of edema. Intellia treatment is given once as a one-hour infusion, making the changes directly in the liver.
Intellia said the single treatment reduced seizures by 87% compared to a placebo, meeting the study’s primary goal. Six months after treatment, 62% of patients were seizure-free and not using other therapies, Intellia said.
The company rated the treatment’s safety and tolerability as “favorable,” reporting that the most common side effects were infusion-related reactions, headache and fatigue. Analysts were closely monitoring the safety of the trial since a patient in a separate trial of a different Intellia treatment died. This patient developed liver injury and ultimately died of septic shock from an ulcer, according to the company.
“When you think about where we started with Crispr, just 12 years ago, with some of the foundational information, 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 an indication with Crispr in vivo where you’re actually changing a gene that causes disease,” said John Leonard, CEO of Intellia.
The only Crispr medication approved by the FDA is from Vertex Pharmaceuticals. Called Casgevy, gene editing is done outside the body, or ex vivo. The process requires collecting a person’s blood cells, making the changes outside the body, and then injecting them back into the patient. Intellia’s treatment, on the other hand, makes the changes inside the body or in vivo.
Intellia said it has launched a rolling application to the FDA and expects to finalize the filing in the second half of this year. The company plans to launch the treatment in the United States in the first half of next year, if approved.
If approved, Intellia’s treatment, lonvoguran ziclumeran, will compete with about a dozen other chronic HAE drugs. Despite the appeal of a one-time treatment, genetic drugs have not always been commercially successful. 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 the fact that BioMarin’s therapy faced questions about how long the effects last. In contrast, he said Intellia hasn’t seen a single case in nearly six years 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 a change. [and] it’s permanent,” Leonard said. “And, to our knowledge, we don’t have a single patient in this program or any other program where the effect of what we did on the gene or the effect of what we saw with the clinical aspects of the disease itself has diminished. So it’s pretty exciting.”
Clarification: This story has been updated to clarify that a patient in a separate trial of a different Intellia treatment developed acute liver injury and ultimately died of septic shock following an ulcer.