Roberto Calicchio has been studying lupus for nearly 30 years. He has witnessed steady but slow progress in understanding and treating this frustratingly complex autoimmune disease.
The past few years have been different. Promising early studies A study by a team of German scientists found that a cell therapy could put lupus into remission in a way that other drugs could not. The discovery sparked industry interest and Approximately 12 clinical trialsMany more are on the way.
“This is unprecedented,” said Calicchio, chief of rheumatology at the University of Massachusetts Chan Medical School. “Sometimes you have to sit down and take a deep breath.”
The latest evidence was presented last week when leading scientists and physicians in autoimmune disease research gathered in Austria for the annual meeting of the European Federation of Rheumatology. Georg Schett, whose team at Friedrich-Alexander University in Erlangen-Nuremberg, Germany, kicked off the current buzz, presented new results from his team’s research at the start of the meeting. Data shows that cell therapy continues to benefit nearly all patients treated for several autoimmune diseases, with some patients experiencing remission for up to three years.
“I’m very excited,” Schett said at a press conference Friday. “When I started this three years ago, I had no idea what it would be like.”
A number of companies, including Kyverna Therapeutics, Cabaretta Bio and Novartis, are hoping to show that Schet’s findings are just the beginning. At the conference, the companies shared updates on clinical studies of so-called CAR-T therapies for autoimmune diseases such as lupus, myositis and systemic sclerosis.
The new results, from a small clinical trial, represent the very early stages of what will likely take years to prove that these therapies, made from a patient’s own cells and proven effective against certain cancers, can reconstitute the immune systems of people with inflammatory diseases. The results suggest the approach’s potential but also the high hurdles drug companies must overcome to succeed.
For example, Cabaretta: The first two treated With CAR-T therapy, one patient will no longer need other medications and the other will be able to wean off steroids. reported similar results Six of seven lupus patients who received CAR-T therapy saw results, some of whom had been treated more than six months prior. Another patient, who had myasthenia gravis, has had no signs of disease or required any other medications a year after treatment.
“We’re seeing this talk about an ‘immune reset’ starting to take shape in some way,” Kiberna CEO Peter Maag said in an interview.
Similar encouraging responses to CAR-T have been reported in other trials. Novartis Biotechnology companies iCell Gene Therapy and JW Therapeutics.
Throughout these trials, participants have experienced mostly mild CAR-T-related immune and neurological side effects, a situation that is reassuring to researchers, as patients with autoimmune diseases have a lower risk tolerance than those with deadly cancers.
“We were pretty scared about potential safety issues” before the trials began in 2021, Schett, who serves on Kaivana and Cavaretta’s scientific advisory board, said Friday. “We feel a lot more at ease now.”
Still, the introduction of cell therapy presents significant obstacles, as effective treatments for autoimmune diseases already exist: CAR-T drugs remain expensive, complex to manufacture, and available only at specialized treatment centers. Second malignancies Symptoms like those rarely reported among cancer patients who receive CAR-T may also occur in people with autoimmune diseases.
Cell therapy “shows great promise, but we don’t know that we would adopt it as a first, second or even third choice,” said Daniel Wallace, chief of rheumatology at City of Hope and Cedars-Sinai Medical Center, who is not involved with any of the companies currently researching autoimmune cell-based therapies.
“If we can put patients with life-threatening organ disease into remission for years,” the treatment is worthwhile, he said.
So analysts are watching to see how much these treatments will free people from the need for many of the immunosuppressants they normally take. At EULAR, Shet said one myositis patient relapsed after 18 months of follow-up; meanwhile, Kyvana said one lupus patient treated by the company relapsed after five months. Nine people who were treated by Kyvana in trials for various diseases, including the lupus patient, are still taking some form of immune drug. They’ve either experienced a relapse or their disease has progressed further. In the latter case, it could take longer for the CAR-T therapy to take effect, said James Chan, chief medical officer.
Dr. Cavaretta reported that two patients with lupus and myositis who received the treatment saw improvement in their symptoms, but neither have yet been cured.
Wall Street analysts were largely impressed with the results. Jefferies’ Kelly See said the Cavaretta data “achieved its goal” of replicating Schett’s results. Leerink Partners’ Thomas Smith noted that the majority of patients receiving Kyvana’s treatment had a “remarkable response,” and the numbers could improve over time. But shares of both companies fell double digits on Friday, with Kyvana’s shares plummeting 34%.
Kyverna argues that the reported relapses were due in part to the low dose levels the subjects were given. Maag also noted that lupus patients often have “multiple things going on” and need treatment. Some researchers prefer to keep patients on low doses of oral steroids, which Kyverna’s trial allowed. Over time, more patients will likely stop taking other medications, Maag said.
“The ultimate goal is to taper off steroids completely,” he said.
“There will be side effects,” Cavaletta Chief Executive Officer Steven Nichtberger said on a conference call with analysts on Friday. “We may not be able to treat some patients effectively, but that’s OK as long as the medicine we have is as good or better than what our peers have.”
Many questions remain about the autoimmune cell therapy. Calicchio of the University of Massachusetts noted that the treatment hasn’t been tested in many black people, who are more likely to suffer from severe forms of lupus. He noted that people with particularly severe kidney problems, a hallmark of the disease, may be less likely to benefit. And while the infections seen in tests have so far been mild, they will need to be monitored, he said.
Other personalized cell therapy trials in progress include treatments made from donor cells or natural killer cells, as well as dual-targeted antibody drugs called T-cell engagers, both of which are seen as more convenient and easier to manufacture options that some analysts believe could rival CAR-T therapies. A similar trend is playing out in oncology, where enthusiasm for CAR-T has been tempered by the success of other technologies.
“This is the first CAR-T approach. It’s proof of concept and shows it works against systemic autoimmunity,” Calicchio said. “I truly believe the next decade will be a life-changing experience for physicians and patients.”
