Novartis, BMS halt autoimmune CAR-T trials
Novartis paused CD19 CAR-T trials after three patient deaths, and Bristol Myers Squibb halted enrollment in a similar program due to inflammatory events.
Novartis has temporarily halted development of its autologous CD19 CAR-T therapy, rapcabtagene autoleucel (rap-cel), for autoimmune diseases. The decision, confirmed on Monday, follows three patient deaths from complications of serious immune effector cell-associated hemophagocytic syndrome (IEC-HS).
Bristol Myers Squibb has also paused enrollment in its trials for an autologous CD19-targeted CAR-T, zola-cel. A company spokesperson told Fierce Biotech the pause was due to "transient and reversible inflammatory events" and was implemented out of an abundance of caution.
Trial Details and Safety Hold
The Novartis hold affects multiple phase 2 and phase 1/2 studies. Screening, randomization, and treatment administration are stopped. The company stated the temporary halt allows for a comprehensive review of clinical and safety data. Patient safety remains the highest priority, and treated patients will continue to be monitored per protocol.
The affected Novartis trials are listed below.
| Disease/Condition | Study Identifier |
|---|---|
| Systemic lupus erythematosus/lupus nephritis | CYTB323J12201 |
| Systemic sclerosis | CYTB323K12201 |
| ANCA-associated vasculitis | CYTB323I12201 |
| Idiopathic inflammatory myopathies | CYTB323L12201 |
| Rheumatoid arthritis and Sjogren’s disease | CYTB323M12101B |
| Generalized myasthenia gravis | CYTB323O12101 |
| Relapsing multiple sclerosis | CYTB323N12101 |
| Non-active progressive multiple sclerosis | CYTB323R12101 |
Novartis confirmed its ongoing oncology program for rap-cel is not affected by this halt. That program is in phase 1/2 trials for blood cancers including chronic lymphocytic leukemia and diffuse large B-cell lymphoma.
Mechanism and Manufacturing Platforms
Rap-cel is designed to reprogram a patient's own T cells to eliminate CD19-expressing B cells. It is manufactured using Novartis's T-Charge platform. This rapid manufacturing system aims to produce fewer exhausted T cells and eliminates extended culture time outside the body.
Bristol Myers Squibb's zola-cel also targets CD19 and uses a similar mechanism to its approved cancer therapy, Breyanzi. It was developed using BMS's NEXT T platform, designed to encourage more uniform and potent T cells for a deeper response.
Analysts from William Blair suggested a possible link between the platforms and the toxicities. In a client note, they indicated that rapid manufacturing could be driving increased cell expansion and the reported toxicities.
Competitive Landscape
The CD19 CAR-T space for autoimmune diseases is active. Cabaletta Bio aims to submit its autologous candidate, resecabtagene autoleucel (rese-cel), for approval in the second half of next year to treat myositis.
Earlier this year, Miltenyi Biomedicine reported its asset, zorpocabtagene autoleucel (zorpo-cel), drove three autoimmune diseases into remission in one patient. Fate Therapeutics also recently reported improvements in patients with treatment-resistant systemic sclerosis dosed with its off-the-shelf candidate, FT819.
BMS stated it is focused on completing its evaluation and resuming enrollment as quickly as possible.
