The results of the CRISPR-Cas9 gene editing study support further development for the treatment of hereditary angioedema

A single treatment with CRISPR-Cas9-based gene editing therapy is enough to replace the daily medication regimen of patients with hereditary angioedema (HAE), a condition characterized by severe, painful and sudden onset swelling that sometimes lead to death.

This confirms findings published earlier this year by researchers at Amsterdam UMC, the University of Auckland and Cambridge University Hospitals NHS Foundation Trust. This phase II study was published in New England Journal of Medicine and will be presented on October 26 at the annual meeting of the American College of Allergy, Asthma & Immunology.

“The results of this double-blind, placebo-controlled portion of the study confirm our promising findings from the Phase I trial and demonstrate a dramatic reduction in angioedema swelling following a single-dose treatment with this gene editing-based therapy,” says Danny Cohn, internist at Amsterdam UMC and first author of the study.

As an extension of the Phase I study, which included ten patients, researchers from around the world led by the Amsterdam UMC tested the CRISPR-based therapy on 27 patients at two different doses compared to placebo. They found that both doses resulted in a reduction in angioedema attacks as well as a sustained and significant reduction in kallikrein levels in HAE patients.

“This reduction is perhaps the most important because it shows us that the therapy is working. Kallikrein acts as a messenger that triggers swelling, and in patients with HAE, this protein is essentially released. The fact that we can reduce its presence shows us that.” “We are on the right track,” says Dr. Hilary Longhurst, honorary lecturer at the University of Auckland.

HAE affects an estimated 50,000 patients worldwide and this rarity often leads to misdiagnosis. This is also one of the reasons why this study involved national centers of excellence from a variety of countries, including the aforementioned partners from the United Kingdom and New Zealand, as well as Australia, Germany and France, as well as an industry sponsor, Intellia the United States.

“For many decades, patients with HAE had only a very limited number of treatment options available to control angioedema attacks. The prospect of a possible, functional cure after a single treatment is overwhelming for both patients and physicians,” says Cohn.

Dr. Padmalal Gurugama, Cambridge University Hospitals NHS Foundation Trust consultant in clinical immunology and allergy, described phase II of the trial as another “fantastic team effort” from clinicians around the world and their patients.

“The results from Phase II build compellingly on those from Phase I and offer real hope to patients suffering from a disease for which there have been very few treatment options. It is absolutely important for patients and the doctors who care for them that this is the case. “The groundbreaking work continues,” he adds.

This expert work continues as the CRISPR-Cas9 therapy NTLA-2002 moves into the third phase of the clinical development program. This study will include more patients and will be conducted again by the same international research group.