Federal rules do not require drugmakers to disclose trial pauses to the public
Bristol Myers Squibb and Novartis have paused clinical trials of their experimental CAR-T therapies for autoimmune diseases, the companies confirmed this week. Novartis paused its rap-cel research last month after three patients died of a rare complication in which the immune system overreacts. Bristol Myers paused its zola-cel program in early June after cases of ICANS, a form of brain inflammation that a company spokesperson described as “transient and reversible” and said were not fatal.
It took roughly three months for Bristol Myers to share that pause with the broader public. Novartis confirmed its own pause only after a Wall Street analyst noticed the trials had gone dark in a public database; it then took about a week for Novartis to reveal that three study patients had died.
Both drugmakers are studying new forms of faster-to-produce CAR-T therapy for autoimmune diseases — a promising area of drug research that re-engineers a patient’s own cells to attack disabling conditions such as lupus or rheumatoid arthritis. Bristol Myers’s pause followed cases of ICANS, a form of brain inflammation, while Novartis’s deaths stemmed from a rare complication in which the immune system overreacts. Both complications are known risks of CAR-T therapy, which is already on the market to treat some cancers.
Novartis is studying rap-cel in eight autoimmune trials, including in multiple sclerosis and rheumatoid arthritis — a broad bet that has enrolled more than 500 patients. Bristol Myers’s safety signal emerged in a trial of zola-cel in patients with a type of lupus, but the company has halted studies into other autoimmune conditions that cause inflammation and muscle weakness.
A Bristol Myers spokesperson said in response to an inquiry that, “as part of routine safety surveillance, we voluntarily paused enrollment and treatment.” The spokesperson described the cases as “transient and reversible” and said none was fatal. Novartis has not answered questions about whether the deaths occurred in one clinical trial or across several, and it is unclear whether the patients died as a result of taking the drug or from underlying conditions. A Novartis spokesman said “broader communication about trial events is balanced with the need to preserve the integrity of ongoing trials” and that the company was “analyzing all data to understand potential factors contributing to recent events.”
The pauses surfaced publicly because of routine database monitoring by a sell-side analyst. Sami Corwin, a biotech analyst at William Blair, was conducting a routine check of clinical trials last week when she saw that a slate of studies testing therapies in autoimmune diseases had gone dark. She started calling around. A colleague noticed that Bristol Myers’s trials had frozen, too. By the weekend, her team had confirmed pauses at both companies.
Corwin published a research note that was picked up by a trade publication; Endpoints News subsequently reported the deaths in Novartis’s trial. Novartis had not told Corwin the cases were fatal when she first asked about the trial pause. “That was news to me,” she said.
Federal rules require companies to report cases such as these to regulators on a tight clock, but there is no equivalent requirement to alert outside parties such as doctors, prospective patients or investors unless the company thinks the information is material to its bottom line. The arrangement gives drugmakers discretion over when to disclose problems — even when hundreds of patients are already enrolled in a study or deciding whether to sign up.
“We’re suffering from a lack of shared knowledge,” said Sue Chrysogelos, who participated in a CAR-T study for a different drugmaker to treat her scleroderma. “For the patients who are in line for this stuff, it’s that balance of are they holding out hoping that they can still get into the trial and is it worth the risk,” she said.
CAR-T has offered the possibility of a single treatment that resets the immune system for life — a contrast to decades of treating autoimmune diseases such as lupus and rheumatoid arthritis with drugs that suppress the immune system and wear down the body. In an early Bristol Myers study of just over 100 patients, more than 90% of patients with treatment-resistant autoimmune disease went into remission without needing further treatment, the company said last year. Those results supported its move into the larger trials that have now been paused.
Dr. Anca Askanase, who is working on the trial in which Bristol Myers noticed the adverse events, said she has received a letter from the company outlining details about the trial pause. She declined to share more information because she had signed a confidentiality agreement with the New Jersey-based drugmaker. “We’re really holding our breath to learn more because there is a lot of interest,” said Askanase, rheumatology chief at the Hospital for Special Surgery in New York City. “Every piece of information is critical.”
Luke Evnin, chair of the San Francisco-based Scleroderma Research Foundation, said he understood that potential legal and regulatory exposure might make the companies cautious about what they say — but that he would be “surprised if they don’t have to come up with an answer for everybody.”
Doctors running the trials are hunting for answers of their own, particularly around what sets the paused therapies apart from similar ones already in wide use for oncology. In conventional CAR-T, a patient’s cells are grown in a lab over several weeks and infused back, a process that allows them to do most of their growth outside of the body. Novartis’s manufacturing platform compresses that growth process into as little as a day, said Oppenheimer analyst Kostas Biliouris, selecting immune cells engineered to multiply aggressively once inside the body — which might be what’s triggering a dangerous immune response. Novartis did not respond to questions about its manufacturing platform. Bristol Myers disputes that its therapy has the same issues; the company said it uses a different platform that takes roughly five days and is designed to let cells stabilize before infusion.