by Amsterdam University Medical Centers

Credit: Pixabay/CC0 Public Domain

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

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

"The results of this double-blind, placebo-controlled portion of the study confirm our promising findings from the Phase I study, showing dramatic reductions of angioedema swellings following a single-dose treatment with this gene editing-based therapy," says Danny Cohn, internist at Amsterdam UMC and first author of the study.

Expanding on the Phase I study, which included 10 patients, researchers from across the world led by Amsterdam UMC, tested the CRISPR-based therapy on 27 patients with two different dosages compared to placebo. They found that both dosages led to a reduction in angioedema attacks as well as a sustained and meaningful reduction in kallikrein levels in HAE patients.

"This reduction is perhaps the most crucial as it shows us that the therapy is working. Kallikrein acts as a messenger that triggers swelling and in patients with HAE, this protein is basically let loose. The fact that we can reduce its presence tells us that we're on the right track," says Dr. Hilary Longhurst, an honorary senior lecturer at the University of Auckland.

HAE affects an estimated 50,000 patients worldwide and this rarity often results in misdiagnosis. It's also part of the reason why this trial included national excellence centers from a wide range of nations including, as well as the aforementioned partners from the United Kingdom and New Zealand as well as Australia, Germany and France and an industry sponsor, Intellia, from the United States.

"For many decades, patients with HAE were faced with a very limited number of treatment options to control angioedema attacks. The prospect of a potential, functional cure following a single-time treatment is overwhelming both for patients and physicians," says Cohn.

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

"The results from Phase II convincingly build on those from Phase I, and offer real hope to patients suffering from a condition that until now had very few treatment options. It is absolutely vital for patients, and those clinicians who care for them, that this game-changing work continues," he adds.

This expert work will continue as the CRISPR-Cas9 therapy NTLA-2002 moves into the third phase of the clinical development program. This trial will include more patients and once again be executed by the same international group of researchers.

More information: Danny M. Cohn et al, CRISPR-Based Therapy for Hereditary Angioedema, New England Journal of Medicine (2024). DOI: 10.1056/NEJMoa2405734

Journal information: New England Journal of Medicine 

Provided by Amsterdam University Medical Centers