Novartis, Bristol Myers face scrutiny over delayed CAR-T trial disclosures

Novartis ↗ 0.77% and Bristol Myers Squibb Bristol-Myers Squibb Company ↗ 0.85% have paused multiple clinical trials testing CAR-T cell therapies in autoimmune diseases, following three patient deaths and other serious safety incidents that have sent shockwaves through a field once seen as one of the most promising frontiers in medicine.

Novartis suspended eight trials of its experimental therapy rapcabtagene autoleucel, known as rap-cel, on August 24 after being notified of three fatal cases of immune effector cell-associated hemophagocytic syndrome, or IEC-HS, a rare and life-threatening immune overreaction. Bristol Myers separately froze enrollment in its zola-cel autoimmune program after detecting what it called "transient and reversible inflammatory events" during routine safety monitoring.pharmavoice+2

A Wall Street Journal News Corp ↗ 0.59% investigation published on September 3 raised troubling questions about the pace of disclosure. According to the report, Bristol Myers informed regulators and researchers of its trial halt in early June but did not communicate the pause publicly until three months later. Novartis, meanwhile, only acknowledged the three deaths after a Wall Street analyst uncovered the suspension in a clinical trial database — and even then took a week to disclose the fatalities.wsj

A Rapidly Expanding Field Faces a Reckoning

CAR-T therapies, which reprogram a patient's own immune cells to attack diseased targets, have already transformed treatment for certain blood cancers. Researchers had been racing to apply the same approach to autoimmune conditions such as lupus, myasthenia gravis, multiple sclerosis, and systemic sclerosis.biopharmadive+1

Multiple analysts have pointed to the rapid manufacturing process used by both Novartis and Bristol Myers as a possible factor in the safety events. Both companies employed a faster lentiviral-based approach to produce modified cells, which some experts believe may generate more inflammatory cells than traditional methods. Jefferies analyst Roger Song noted that autoimmune patients already have heightened immune activity at baseline, which CAR-T therapies could push into overdrive.pharmavoice

Smaller Developers Seek to Distance Themselves

The trial halts triggered sharp but temporary stock declines in companies developing rival autoimmune cell therapies, including Kyverna Therapeutics ↗ 6.56%, Cabaletta Bio ↗ 17.69%, and Allogene Therapeutics ↗ 2.88%. Each moved quickly to differentiate its approach. Kyverna emphasized that its lead therapy uses "a distinct construct design" with "a well-established, validated manufacturing process". TD Cowen analyst Phil Nadeau noted that Cabaletta's standardized nine-day production process was specifically designed to "minimize immune related toxicities," and that the company has seen no cases of IEC-HS.pharmavoice

Novartis said it is conducting "a comprehensive review of the observed safety events" and is engaged with regulators. The pause does not affect ongoing cancer studies of rap-cel. Bristol Myers said it aims to complete its evaluation and resume testing "as quickly as possible".cgtlive+2

Transparency Under Scrutiny

The delayed disclosures may draw regulatory attention. The WSJ report highlighted a pattern in which companies communicated safety problems to regulators and advocacy groups well before informing the public or the broader investment community. As the field grapples with the safety setbacks, the episode has underscored a tension at the heart of experimental medicine: the promise of transformative treatments weighed against the risks patients bear — and how quickly those risks are made known.wsj