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Hilary Longhurst
Senior Medical Officer, Immunology, Te Toki Tumai/Health NZ Dr. Hilary Longhurst is currently Senior Medical Officer in Immunology for Te Toka Tumai/ Health New Zealand and Honorary Associate Professor at the University of Auckland. She qualified in medicine from Cambridge University and Imperial College, London and developed her interest in Immunology while studying for her PhD at the National Institute for Medical Research (now the Crick Institute). She has been instrumental in developing patient-centred services for those with hereditary angioedema due to C1 inhibitor deficiency. Being involved in most major HAE trials in the past 20 years, she has been a pioneer in developing and enabling access to the new therapies, which have transformed the lives of many people with this disabling disorder.
Hilary also has clinical and academic interests in primary and secondary antibody deficiency and serves as medical advisor to DC Action, a charity supporting those with telomere biology disorders. |
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In Vitro CRISPR-Cas9 Gene Editing for Hereditary Angioedema
Introduction: Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent, debilitating and potentially fatal swelling attacks. Prophylactic treatments targeting kallikrein, a protease encoded by the KLKB1 gene, reduce the frequency of attacks. NTLA-2002 is an investigational CRISPR/Cas9-based therapy targeting KLKB1 in hepatocytes, with the goal of life-long control of HAE attacks after a single administration.
Methods: NCT05120830 is a first-in-human phase 1/2 study of NTLA-2002 in patients with HAE. The phase 1 is a single-ascending dose design with the primary objective of evaluating safety and identifying two doses to advance to the randomized phase 2 for further evaluation of efficacy and safety.
Results: 10 subjects (25 mg; n = 3, 75 mg; n = 3, 50 mg; n = 4) completed the 16-week primary observation period. No dose-limiting toxicities (DLTs) or clinically significant laboratory abnormalities were observed. Treatment-emergent adverse events were non-serious and spontaneously resolving; the most common being infusion-related reactions. All subjects demonstrated clinically significant, durable reduction in plasma kallikrein levels and HAE attack frequency, from baseline. Enrolment has started for the double-blind, placebo-controlled phase 2 study.
Methods: NCT05120830 is a first-in-human phase 1/2 study of NTLA-2002 in patients with HAE. The phase 1 is a single-ascending dose design with the primary objective of evaluating safety and identifying two doses to advance to the randomized phase 2 for further evaluation of efficacy and safety.
Results: 10 subjects (25 mg; n = 3, 75 mg; n = 3, 50 mg; n = 4) completed the 16-week primary observation period. No dose-limiting toxicities (DLTs) or clinically significant laboratory abnormalities were observed. Treatment-emergent adverse events were non-serious and spontaneously resolving; the most common being infusion-related reactions. All subjects demonstrated clinically significant, durable reduction in plasma kallikrein levels and HAE attack frequency, from baseline. Enrolment has started for the double-blind, placebo-controlled phase 2 study.
