What's Happening?
Intellia Therapeutics has reported the death of an elderly patient involved in its Phase III trial for the CRISPR-based therapy nexiguran ziclumeran (nex-z), aimed at treating transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The patient, described
as a man in his early 80s with a high body mass index, experienced severe liver dysfunction, including Grade 4 liver transaminases and increased bilirubin levels, after receiving the treatment. Following this incident, Intellia has paused dosing and screening in the MAGNITUDE trial and a related study, MAGNITUDE-2. The FDA has imposed a clinical hold on the trials, and Intellia is awaiting a formal letter from the agency. The company is working with clinical investigators to understand the liver-related events and develop a risk mitigation plan.
Why It's Important?
The incident raises significant concerns about the safety of CRISPR-based therapies, particularly those targeting the TTR gene. The death has led to a sharp decline in Intellia's stock value, reflecting investor apprehension about the future of the company's gene-editing programs. The broader implications for the TTR program are substantial, as the safety concerns could impact the development and approval of similar therapies. The situation underscores the challenges in advancing gene-editing technologies and the importance of rigorous safety evaluations. The outcome of this case could influence regulatory approaches and investor confidence in the biotechnology sector.
What's Next?
Intellia plans to provide an update after receiving the FDA's clinical hold letter and finalizing a plan with regulators. The company is also increasing monitoring of patient laboratory values in ongoing trials. Meanwhile, Intellia is preparing to present long-term safety and efficacy data for nex-z at the American Heart Association Scientific Sessions. The resolution of this issue will be closely watched by stakeholders in the biotech industry, as it may set precedents for future gene-editing trials and regulatory standards.
