Patient Death in Intellia's CRISPR Trial Halts Phase 3 Studies

Intellia Therapeutics faces a significant setback as a patient death in its phase 3 clinical trial for the CRISPR-based therapy nex-z leads to a halt in dosing. The incident raises concerns about the therapy's safety profile and potential market impact.

Trial Suspension and Patient Death

Intellia Therapeutics announced the death of a patient who had been hospitalized after receiving the company's CRISPR therapy nex-z. The patient, a man in his early 80s with transthyretin amyloidosis with cardiomyopathy (ATTR-CM), died on Wednesday night. This event follows the recent pause in dosing for both phase 3 studies of nex-z, which was initiated after the patient experienced grade 4 liver enzymes and increased total bilirubin.

The U.S. Food and Drug Administration (FDA) has placed both trials on clinical hold as Intellia works to understand the liver-related events observed in the studies and develop a risk-mitigation plan. CEO John Leonard, M.D., disclosed that the deceased patient had bilirubin and ALT levels two and three times the upper limit of normal, respectively.

Safety Concerns and Market Implications

The safety signal has raised questions about the therapy's future. Intellia reports that less than 1% of the more than 650 patients enrolled in the ATTR-CM trial experienced grade 4 elevated liver enzymes. No such cases were observed among the 47 patients in the ATTR with polyneuropathy trial.

However, analysts from Guggenheim Securities have suggested that these adverse events could "severely limit the commercial potential of nex-z." The uncertainty surrounding the mechanism of these events implies they could occur in commercial settings, potentially impacting the therapy's market prospects.

Intellia faces competition in the ATTR market from established players such as Alnylam Pharmaceuticals, BridgeBio, and Pfizer. The company's stock reflected investor concerns, falling 24% to $9.33 in premarket trading on Friday.

Next Steps and Financial Outlook

Intellia is implementing additional safety measures, including more frequent lab collections from patients in the initial weeks post-dosing to detect potential liver enzyme elevations earlier. The company aims to develop criteria to exclude patients who may be at higher risk for adverse events.

Despite the setback, Intellia maintains its financial stability. CFO Edward Dulac stated that the company does not anticipate substantial changes in operating or cash needs. With $670 million in reserves, Intellia expects to fund operations into mid-2027.

As the pharmaceutical industry watches closely, the resolution of this safety concern and the resumption of the nex-z trials remain uncertain, potentially impacting the broader landscape of CRISPR-based therapies in development.