Drugmakers Halt Autoimmune Trials After Deaths, Life-Threatening Side Effects
Trial freezes by Novartis and Bristol Myers have triggered race to understand why promising autoimmune treatment turned risky
- Novartis and Bristol Myers Squibb paused clinical trials for their experimental autoimmune CAR-T therapies due to serious safety concerns.
- Federal rules do not require drugmakers to immediately disclose clinical trial pauses to the public, giving companies discretion over what they share.
- Information about clinical trials can be commercially competitive, so companies guard it closely.
Bristol Myers Squibb told regulators, researchers and patient-advocacy groups in early June that it had paused closely watched drug research because of life-threatening side effects. It took three months for the company to share that with the broader public.
Novartis paused research into a similar therapy last month, which it confirmed only after a Wall Street analyst noticed while scouring a database. It took a week for the company to reveal that three study patients had died.
Novartis and Bristol Myers are both studying their own new forms of faster-to-produce CAR-T therapy for autoimmune diseases, a promising new area of drug research that re-engineers a person’s own cells to attack disabling conditions such as lupus or rheumatoid arthritis.
In Novartis’s trial, three people died of a rare complication in which the immune system overreacts. Bristol Myers’ zola-cel pause, announced this week, followed a different complication called ICANS, a form of brain inflammation. Both are known complications of CAR-T therapy, which is already on the market to treat some cancers.
“As part of routine safety surveillance,” a Bristol Myers spokesperson said in response to an inquiry, “we voluntarily paused enrollment and treatment.”
Drugmakers aren’t required to tell the public when an experimental treatment turns dangerous. 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. That gives drugmakers discretion over when to say if they spot 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.
Information about clinical trials can be commercially competitive, so companies guard it closely. When trials are paused without disclosure, though, patients can get stuck waiting without much clarity about the potential risks of participating.
“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,” Chrysogelos said.
Novartis is studying its therapy 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.
It took a Wall Street analyst noticing something odd in a database to surface the halted research.
Sami Corwin, who covers biotech for William Blair, was doing 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 got picked up by a trade publication and shortly thereafter, Endpoints News reported the deaths in Novartis’s trial.
Novartis hadn’t told Corwin the cases were fatal when she asked about the trial pause, Corwin said. “That was news to me.”
The company hasn’t answered questions about whether the deaths in Novartis’s studies occurred in one clinical trial or across several. It is unclear whether the people died as a result of taking the drug or from underlying conditions.
“Broader communication about trial events is balanced with the need to preserve the integrity of ongoing trials,” a Novartis spokesman said, adding that the company was “analyzing all data to understand potential factors contributing to recent events.”
A Bristol Myers spokesperson described its cases as “transient and reversible” and said none was fatal.
For decades, treating autoimmune diseases such as lupus and rheumatoid arthritis has meant a lifetime of drugs that suppress the immune system and wear down the body. CAR-T has offered the possibility of a single treatment that resets the immune system for life.
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 were 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.”
The lack of detail has alarmed advocacy and research groups that typically stay in regular contact with both companies.
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 didn’t respond to The Wall Street Journal’s questions about the company’s manufacturing platform.
Bristol Myers disputes that its own 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.
