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Raised liver enzymes were a factor during Intellia Therapeutics\' phase 1 trial of nex-z in ATTR.\n Intellia Therapeutics’ stock may have taken a hit in the wake of details of a grade 4 adverse event in a phase 3 trial, but analysts are keeping faith in the gene therapy’s wider safety profile.The biotech used a Securities and Exchange Commission filing May 28 to provide an update on a trio of late-stage trials of its candidate nex-z. This included a study in transthyretin amyloid cardiomyopathy (ATTR-CM), which has seen more than 200 patients dosed to date.So far, the reported adverse events have been “similar in nature” to a phase 1 trial of the drug in ATTR-CM, Intellia said. These events have included infusion-related reactions and asymptomatic liver transaminase elevations, a term for raised levels of the ALT and AST enzymes that can be a sign of liver stress.One of the cases of raised liver transaminase was classed as grade 4—the most serious level of nonfatal adverse event. This recent event was asymptomatic and was identified by laboratory tests, according to Intellia. It then appeared to resolve without the need for hospitalization or medical intervention, and the ALT and AST enzyme levels of this individual are currently classified as grade 3 and 2, respectively.Still, the details appeared to trigger a sell-off of Intellia’s stock, which was 23% in the red in premarket trading Thursday morning. William Blair analysts branded the grade 4 event “obviously disappointing” and suggested the stock drop meant “there will be outstanding question about safety moving forward.”“However, we believe the asymptomatic nature of these elevations and low incidence still plays out for a favorable risk/benefit for nex-z in TTR amyloidosis,” the analysts added in a May 29 note. “Yes, there are other effective treatment options here with TTR stabilizers and silencers, so safety will be a consideration moving forward in this indication, but … we continue to see nex-z’s TTR knockdown profile as impressive and de-risking a positive clinical outcome.” As Intellia alluded to in yesterday’s filing, raised enzyme levels were a factor during its phase 1 trial of nex-z in ATTR, leading the company to add a lower fixed dose level to the polyneuropathy arm of that study back in 2022.There are a host of drugs on the market for several versions of ATTR including Alnylam’s Onpattro and Amvuttra, Ionis Pharmaceuticals\' Tegsedi and its AstraZeneca-partnered Wainua, which are used against polyneuropathy (damage to nerves) associated with ATTR. Pfizer’s Vyndaqel is also approved to help stabilize the transthyretin protein for cardiomyopathy associated with TTR.Intellia’s plan remains to submit an approval application to the FDA for nex-z in transthyretin amyloid polyneuropathy (ATTRv-PN) in 2028 with an anticipated U.S. commercial launch in 2029, the biotech said in its filing.  Before that, the company hopes to submit a separate FDA approval application next year for the gene therapy in hereditary angioedema. The company is currently running phase 3 trials in both those indications, in addition to the ATTR-CM study.