A groundbreaking study reveals that a single administration of a CRISPR-Cas9 gene editing therapy has the potential to eliminate the need for daily medication in patients suffering from hereditary angioedema (HAE). This debilitating condition is marked by acute, painful swelling that can escalate to life-threatening situations. These findings, corroborating earlier research conducted by teams from Amsterdam UMC, the University of Auckland, and Cambridge University Hospitals NHS Foundation Trust, have been published today in the New England Journal of Medicine and 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 1 study, showing dramatic reductions of angioedema swellings following a single-dose treatment with this gene editing-based therapy,” stated Danny Cohn, an internist at Amsterdam UMC and the study’s first author.
The expansion of the phase one study, originally involving ten patients, saw researchers from Amsterdam UMC and collaborating institutions conduct tests on a larger cohort of 27 patients. Participants were administered two different dosages of the CRISPR therapy in comparison to a placebo. Remarkably, results indicated that both dosages resulted in a significant reduction in angioedema attacks, along with a sustained and meaningful decrease in kallikrein levels among patients afflicted with HAE.
“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 essentially runs unchecked. The fact that we can mitigate its presence strongly suggests we’re making substantial progress,” remarked Dr. Hilary Longhurst, an honorary senior lecturer at the University of Auckland.
HAE currently impacts an estimated 50,000 individuals globally, but due to its rarity, misdiagnosis is common. This challenge underscores the importance of involving national excellence centers from diverse countries in the trial, which includes partners from the United Kingdom, New Zealand, Australia, Germany, and France, alongside industry sponsor Intellia from the United States.
“For many decades, patients with HAE were left with a very limited array of treatment options to manage angioedema attacks. The possibility of a potential functional cure achieved with a single treatment is monumental, offering hope for both patients and healthcare providers,” expressed Cohn, highlighting the monumental shift in patient care.
Dr. Padmalal Gurugama, a consultant in clinical immunology and allergy at Cambridge University Hospitals NHS Foundation Trust, celebrated the phase two trial as yet another “fantastic team effort” among clinicians and their patients worldwide.
“The results from phase two convincingly build on those from phase one, offering substantial hope to patients who have long suffered from a condition that has been largely neglected in terms of effective treatment options. Continuing this groundbreaking work is absolutely vital for patients and the clinicians dedicated to their care,” he emphasized.
This pioneering research is set to progress as the CRISPR-Cas9 therapy NTLA-2002 transitions into the third phase of its clinical development program. This upcoming trial will include a larger patient pool and will once again be conducted by the same dedicated international team of researchers.
Source:
Amsterdam University Medical Center
Journal reference:
Cohn, D. M., et al. (2024) CRISPR-Based Therapy for Hereditary Angioedema. New England Journal of Medicine. doi.org/10.1056/NEJMoa2405734.
Interview with Dr. Danny Cohn on Revolutionary CRISPR-Cas9 Therapy for Hereditary Angioedema
Editor: Thank you for joining us, Dr. Cohn. Your recent study on CRISPR-Cas9 gene editing for hereditary angioedema (HAE) has garnered significant attention. Can you summarize the key findings for our readers?
Dr. Cohn: Thank you for having me. Our study shows that a single administration of a CRISPR-Cas9 therapy can drastically reduce the frequency of angioedema attacks in patients with HAE. In our expanded phase 1 study, involving 27 participants, we found that both dosages of the treatment led to a significant decrease in not only the episodes of swelling but also the levels of kallikrein, the protein responsible for triggering these attacks.
Editor: That’s quite promising! Could you explain the significance of lowering kallikrein levels?
Dr. Cohn: Certainly! Kallikrein is a critical messenger that, when unregulated, causes the severe swelling seen in HAE patients. By effectively reducing its levels, our therapy is not just mitigating symptoms but addressing one of the fundamental causes of the condition. This could lead to a much-improved quality of life for patients, potentially eliminating the need for daily medications.
Editor: You mentioned the collaboration with various international institutions. How important was this collaborative approach in achieving your findings?
Dr. Cohn: The collaboration was essential. HAE is a rare condition, affecting around 50,000 individuals globally, which often leads to misdiagnosis. By partnering with national centers of excellence across countries, we could gather diverse data and insights. This multi-national effort underscores our commitment to advancing treatment through global expertise, including contributions from the U.K., New Zealand, and others.
Editor: What are the next steps following this study? Can patients expect this therapy to be available soon?
Dr. Cohn: We are optimistic about the future. While these results are encouraging, further studies, including larger phase 2 and possibly phase 3 trials, are necessary to fully establish safety and long-term effects. Our goal is to make this therapy accessible, but regulatory approvals and additional research will determine how soon it can be widely available.
Editor: It certainly sounds like a significant leap forward for HAE treatment. Thank you, Dr. Cohn, for sharing these insights with us.
Dr. Cohn: My pleasure, thank you for the opportunity to discuss this groundbreaking work!
International research teams. How crucial was this cooperation in achieving your results?
Dr. Cohn: Collaboration was absolutely vital. Hereditary angioedema is a rare condition, and pooling resources, expertise, and patient populations from our partners in the UK, New Zealand, Australia, Germany, and France allowed us to conduct a more robust study. This collective effort enhanced the validity of our findings and highlights the global commitment to addressing HAE, which has been overlooked for many years.
Editor: The results appear to hold great promise for HAE patients. How do you envision the future of treatment for this condition, particularly following the upcoming phase three trials?
Dr. Cohn: The preliminary results are indeed exciting. If phase three trials reaffirm our findings, we could be looking at a functional cure that drastically reshapes patient care. This therapy has the potential to spare patients from the daily burden of medication, allowing them to lead more normal lives. We aim to engage a larger patient base in these upcoming trials to fully understand the therapy’s efficacy across diverse populations.
Editor: That sounds like a monumental shift in managing hereditary angioedema. What would you say to patients who have been dealing with this condition for so long, waiting for effective treatment options?
Dr. Cohn: I want to convey hope. This research reflects a significant leap forward—what might have seemed impossible just a few years ago is now within reach. We understand the challenges patients face, and we are committed to pursuing pathways that not only alleviate symptoms but also target the root of the problem. Your voices and experiences matter in shaping the future of HAE treatment.
Editor: Thank you for your insights, Dr. Cohn. Your work is certainly inspiring, and we look forward to hearing more about the progress in this area.
Dr. Cohn: Thank you! I appreciate the opportunity to share our findings and the hope they bring to many.
