CRISPR Therapy Trials Halted Over Safety Concerns
Intellia Therapeutics has discontinued dosing and screening in 2 phase 3 trials due to a liver safety signal. The halt is in two cohorts of patients with transthyretin amyloidosis (ATTR) of a CRISPR therapy, nex-z, which inactivates the TTR gene. One study is conducting a trial on ATTR and cardiomyopathy (ATTR-CM). The other trial is ATTR polyneuropathy (ATTR-PN).
Details on the Patient’s Condition
The ATTR-CM trial- Intellia halted both trials following a report of grade 4 liver enzymes and an elevated total bilirubin in a patient of the trial. According to the biotech, the patient is in treatment and is under close monitoring since he has been hospitalized.
The biotech has recorded high liver enzymes on the treatment of Nex-Z recipients previously. The combination of liver enzymes and total bilirubin exceeding the threshold created the stopping criteria, and this necessitated a pause this time as Intellia CEO John Leonard explained to the analysts in a telephone call discussing the update.
CEO Addresses Concerns
Leonard stated that the high liver enzymes and bilirubin would qualify as the high liver enzymes and bilirubin according to the old definition of the Hy law, a rule of thumb that evaluates the probability of an injury to the liver caused by drugs.
Intellia has been striving to come up with a plan that will see it re-enroll. As the biotech was just briefed about the adverse incident, the management is still in its infancy in trying to come up with the etiology of the liver safety signal.
Leonard said it was too early to make any kind of predictions as to predictors or populations of patients at risk. It goes without saying that we are investigating this, and we are preparing a list of questions that we are going to ask our [data and safety monitoring board] and other parties.
Investigating the Cause
More than three weeks following administration of nex-z, the patient had high liver enzymes. Leonard indicated that the case and another patient who had asymptomatic elevated liver enzymes had earlier been seen during the phase 3 program had similarities in timing. The hospitalized patient seems to have had the changes that were observed in the other patient, which the CEO referred to as more pronounced.
There is a delay between nex-z administration and the development of high liver enzyme levels. The lipid nanoparticles (LNPs) being used to test the therapy did not most likely cause the adverse events. Small hepatic enzyme raises in patients may occur during the day or two following the administration of LNPs. The timing made Leonard assume that there was another issue at Intellia.
Future of the TTR Program
Leonard believes that the issue lies within the Intellia TTR program. Research into the other candidate of the biotech, lonvoguran ziczlumeran, in hereditary angioedema is ongoing.
It is not quite clear how long Intellia would take to re-launch the TTR trials. Leonard could only guess on the time the pause would last, but said work on the resolution would definitely extend over a period of some weeks.
Any delay will postpone the possible entrance of Intellia into an area that is provided by Alnylam, BridgeBio, and Pfizer. Nex-z may be a one-time substitute for the current treatments in the event of its approval.
Conclusion
In conclusion, the pause of Intellia’s CRISPR-based Phase 3 trials marks a significant inflection point in the gene-editing industry. While the therapeutic promise of CRISPR remains substantial, this development reminds the community that safety remains paramount. For patients with ATTR and other serious conditions, the path forward will be watched closely by regulators, investors and clinicians alike.
The implications of this CRISPR trial interruption go beyond Intellia alone. Investors, biotech observers and patient advocacy groups will all look at how the company responds — whether it can isolate the cause, implement robust safeguards and restart the programme without compromising scientific integrity or safety. The outcome could shape not only Intellia’s future but also the regulatory-and-commercial trajectory of the entire CRISPR therapeutic class.
