Dive Brief:

• Shares for Intellia Therapeutics climbed by about 10% early Tuesday after the company said the Food and Drug Administration cleared it to resume one of two Phase 3 trials evaluating its experimental CRISPR-based treatment against the rare genetic disease transthyretin amyloidosis.   
• U.S. regulators halted two studies of Intellia’s nexiguran ziclumeran, or nex-z, last October following the occurrence of serious liver toxicity that resulted in the death of a trial participant. Intellia said Tuesday that the FDA has allowed it to restart “MAGNITUDE-2,” a trial testing nex-z in people with a form of the disease that affects the nerves, by incorporating new risk mitigation measures. It’s also enrolling about 10 more patients in that study. Intellia aims to begin testing again “as quickly as possible.” 
• Intellia also revealed, however, that a pause in the “MAGNITUDE” trial in patients with the “cardiomyopathy” form of the disease is ongoing. The company will provide an update once aligned with regulators on the program’s path forward there.

Dive Insight:

Intellia, one of the first biotechs built around CRISPR gene editing technology, has long been hoping that nex-z will prove a step forward in care for transthyretin amyloidosis, a condition that causes misfolded protein clumps to accumulate and trigger organ damage. 

Transthyretin amyloidosis can currently be treated by certain injectable and oral treatments that slow progression. Intellia is positioning nex-z as a long-lasting alternative. But since late last year, the program has been slowed by safety concerns that have dimmed investors’ expectations. 

News that at least one of nex-z’s two late-stage trials has been restarted is a “positive” for the company and its ability to negotiate with the FDA, wrote William Blair analyst Myles Minter. Intellia didn’t provide specific details on the agreement, but noted that it agreed to stricter monitoring of liver laboratory tests.

However, investors are also keenly focused on Intellia’s cardiomyopathy trial, which represents a much larger market opportunity. Minter noted that because that form of the disease tends to impact older people with a higher risk of health complications, the FDA might be “more cautious” and could “require more stringent risk mitigation.”

“We continue to believe in the efficacy of Intellia’s platform... but safety events from nex-z have been and will continue to be a stock overhang until further regulatory clarity is gained on resumption of MAGNITUDE and as investors gain comfort with new risk-mitigation strategies,” Minter wrote. 

Intellia is also awaiting results from a Phase 3 study testing a different therapy, dubbed lonvo-z, in a rare swelling condition called hereditary angioedema. Intellia has touted the therapy as a potential “functional cure” for the disease and is expecting Phase 3 results in the first half of this year.