Investigational CAR T therapies stole the spotlight at the American College of Rheumatology Convergence as data presented by Bristol Myers Squibb, Kyverna Therapeutics and more highlighted their potential to effectively treat lupus.
Having proven their worth in several types of blood cancers, autoimmune disease is the next frontier for CAR T therapies. Bristol Myers Squibb, Kyverna Therapeutics, Fate Therapeutics and Cabaletta Bio all presented data on their CAR T candidates for lupus at the American College of Rheumatology Convergence over the past week.
“Lupus remains a challenging disease with limited approved treatments,” Simi Badyal, senior competitive intelligence immunology analyst at GlobalData, told BioSpace in an email. Although the space has seen some evolution with targeted therapy approvals, the disease remains without a cure.
Still in early clinical stages, biopharma companies are banking on CAR T therapies being able to change that.
The CDC estimates around 204,000 people in the U.S. have systemic lupus erythematosus (SLE), the most common type of lupus. The chronic disease causes inflammation throughout the body that can lead to heart and kidney problems, issues with the brain and nervous system and more. Complications can be fatal if left untreated.
“Here at ACR, we feel the excitement around the potential of cell therapy to help offer patients living with severe, uncontrolled autoimmune diseases the chance for durable, treatment-free remissions—something, up until recently, thought to be impossible,” a BMS spokesperson told BioSpace in an email.
BioSpace rounded up key data presented in this space at ACR.
Bristol Myers Squibb
Asset: CC97540
Status: Phase I
BMS’s CD19-directed autologous CAR T therapy depletes B cells in patients to reset their immune system. A Phase I study, presented at ACR, included patients with SLE with inadequate response to glucocorticoids and immunosuppressants. CC-97540 uses the same construct as Breyanzi, BMS’ approved CAR T therapy for various types of lymphomas and leukemias.
The BMS spokesperson said the results showed that CC-97540 “significantly improved” lupus manifestations in the seven SLE patients that were included. All patients have remained off other treatments as of the 11 months follow-up point, with no new signs of disease activity.
Full B cell depletion was achieved by day eight. Participants had reduced SLE activity and both patients and physicians reported quality of life improvements within a month after infusion. Patients treated remained in drug-free remission.
At the conference, the company highlighted one patient who successfully conceived and carried a child to birth after treatment. Around one third of women with lupus have antibodies that cause issues in pregnancy. BMS reported one instance of a grade 3 immune effector cell-associated neurotoxicity syndrome, a known risk factor of CAR T therapy. The case was fully resolved, and the spokesperson said BMS considers the therapy to have a “manageable safety profile with no unexpected adverse events.”
BMS now has two multi-cohort Phase I studies underway to evaluate the safety, tolerability and efficacy of the CAR T therapy in systemic lupus erythematosus, idiopathic inflammatory myopathies and systemic sclerosis.
“We’re encouraged by the potential for patients with severe lupus and other autoimmune diseases to achieve B-cell depletion and significant clinical responses following a single infusion of CAR T-cell therapy, even after discontinuing immunosuppressive treatments,” the spokesperson said.
Kyverna Therapeutics
Asset: KYV-101
Status: Phase I/II ongoing
Kyverna’s CD19 CAR T therapy KYV-101 has shown sustained efficacy and durability in six lupus nephritis patients treated at the target dose. Key findings of the company’s ongoing Phase I/II trial, presented at ACR, show deep B cell depletion, immune system reset, reduced SLE activity, preserved kidney function and stabilized eGFR, an indicator of kidney damage. All patients in the trial were able to eliminate immunosuppressant treatments and reduce glucocorticoids. However, in June, Kyverna disclosed that one patient experienced disease recurrence after five months.
Fate Therapeutics
Asset: FT819
Status: Phase 1 ongoing
Fate Therapeutics is hoping to bring the first off-the-shelf CAR T therapy to patients with autoimmune disease. The biopharma is testing its induced pluripotent stem cell (iPSC)-derived CAR T cell product candidate in a Phase I trial. The study’s first patient had active lupus nephritis and severe disease. Since receiving FT819, the patient achieved clinical remission, had a low lupus disease activity state after six months of follow up and continues on-study free of all immunosuppressive therapies, according to the ACR presentation.
Notably, FT819 is being administered with fludarabine-free conditioning, a drug typically given as part of the lymphodepleting chemotherapy regimen before CAR T therapy.
“Treatment without fludarabine conditioning is an important step to increased uptake in autoimmune diseases, in our view, as the intense regimen can outweigh the benefits for many patients,” BMO Capital Markets analysts said in a Monday note to investors.
Cabaletta Bio
Asset: CABA-201
Status: Phase I/II ongoing
Cabaletta is just getting started on its Phase I/II trial for SLE, having dosed only one patient so far. While it’s still early days, Badyal called the results shared at ACR “promising,” as rapid B cell depletion was seen by day 15 in this patient, with clinical improvements seen by one to three months post-infusion. No severe adverse events were reported.
Cell Therapy’s Potential in Lupus
While CAR T cell therapies are pricey—BMS’s Breyanzi is over $480,000 for one suspension—the potential to have a one-time infusion for a long-lasting, drug-free remission would be highly appealing to lupus patients who otherwise face a lifetime of ongoing medications, Badyal said. Companies working in this space will need to consider how they can make these treatments affordable and accessible.
“The therapies’ effectiveness in cases where all prior treatments have failed, combined with the convenience of a single infusion offering the potential for long-term remission, could make them highly marketable,” she said.
