Gene Therapy Safety Concerns Persist Despite Analysts' Optimism

Intellia's Adverse Event Raises Questions

Intellia Therapeutics faced a significant stock decline following the disclosure of an adverse event in their late-stage gene editing therapy trial for transthyretin amyloidosis. The company reported a case of elevated liver enzymes in a patient treated with nexiguran ziclumeran (nex-z), developed in partnership with Regeneron. This marks the second such incident in the trial, causing Intellia's shares to tumble by 26% at market opening.

Despite the market reaction, several analysts remain optimistic about the therapy's prospects. William Blair analysts acknowledged the disappointment but noted that the adverse event rate across the clinical program is approximately 0.66%. Truist Securities and BMO Capital Markets analysts described the incident as a "non-concern," suggesting that the stock reaction may be more reflective of broader safety concerns in the gene therapy space rather than specific issues with Intellia's treatment.

Recent Patient Deaths Amplify Industry Concerns

The gene therapy sector has been grappling with safety issues following recent patient deaths in clinical trials. Earlier this week, Rocket Pharmaceuticals reported a patient death in their Phase II trial for Danon disease gene therapy RP-A501, leading to a voluntary suspension and FDA hold. Similar incidents have occurred in studies conducted by Sarepta Therapeutics and Neurogene.

These events have heightened scrutiny of gene therapy safety profiles, particularly regarding delivery mechanisms. Analysts at BMO Capital Markets emphasized the distinction between Intellia's lipid nanoparticle (LNP) delivery system and the adeno-associated virus (AAV) vectors used in the trials where fatalities occurred. They stated, "We believe that a single-time LNP administration is likely more safe/predictable/understood than a single-time AAV-based gene therapy."

Debate Over Treatment vs. Delivery Mechanism

The adverse event in Intellia's trial has sparked a debate about whether the treatment itself or the LNP delivery mechanism is responsible. Investigators have deemed the situation as likely related to nex-z. However, the timing of the liver enzyme elevations, which began a week post-infusion and peaked at day 28, suggests that LNP toxicity may not be the culprit.

This incident has also raised questions about the broader implications for LNP-delivered genetic medicines. William Blair analysts remain confident in the risk/benefit profile of nex-z in ATTR but acknowledge that safety will be a key consideration moving forward, especially given the increasing competition in the ATTR treatment landscape.