Phase Two results with CRISPR-Cas9 gene editing support further development as treatment for hereditary angioedema (HAE)

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 from researchers from Amsterdam UMC, the University of Auckland and Cambridge University Hospitals NHS Foundation Trust. This phase two study is published today in the New England Journal of Medicine and presented at American College of Allergy, Asthma & Immunology's annual congress on the 26th of October.  

"The results of this double-blind, placebo-controlled portion of the study confirm our promising findings from the phase 1 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 one study, which included ten 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 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 two of the trail as another “fantastic team effort” by clinicians around the world, and their patients.  

“The results from phase two convincingly build on those from phase one, 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. Read more on the first phase of this research here: Gene-editing offers hope for people with hereditary disorder (amsterdamumc.org)