Systemic Lupus Erythematosus CAR-T Gets FDA Fast Track Designation


Cabaletta Bio’s CABA-201 also recently received clearance from the FDA to initiate a phase 1/2 trial.

Cabaletta Bio’s CABA-201, an investigational CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy intended to treat systemic lupus erythematosus (SLE) and lupus nephritis (LN), has received fast track designation from the FDA.1

CABA-201 contains a 4-1BB costimulatory domain and is intended to deplete B-cells in order to “reset” the immune systems of patients. In March 2023, Cabaletta Bio received clearance of its investigational new drug (IND) application for the therapy from the FDA.2 The company is planning to initiate a phase 1/2 clinical trial which will seek to enroll a cohort of 6 patients with SLE with active LN and a separate cohort of 6 patients with SLE whose disease has no renal involvement. Both cohorts will be treated with a dose of 1x106 CAR-T cells/kg.

“Despite advances over the last few decades, treatment options for SLE remain inadequate,” David J. Chang, MD, the chief medical officer of Cabaletta Bio said in a statement.1 “There are currently no curative options available that achieve durable disease remission. Existing therapies typically result in general immunosuppression, require chronic administration, and are often administered in conjunction with steroids and other immunosuppressive medications to reduce disease burden, which can leave patients with continued disease activity, treatment-associated side effects, and impaired quality of life.”

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“We believe the FDA’s decision to grant fast track designation for CABA-201 underscores the unmet need for a treatment that has the potential to provide deep and durable responses for people living with lupus and potentially other autoimmune diseases where B-cells contribute to disease. We look forward to initiating the phase 1/2 trial for CABA-201 and further evaluating its therapeutic potential for patients in need,” Chang continued.

The clinical trial design is informed by an earlier compassionate use study which treated 5 patients with SLE with a similar CD19-directed CAR-T product at the same dose.3 The study, results from which were published in Nature Medicine in September 2022, found that the patients experienced deep depletion of B-cells and improvement of clinical symptoms following treatment with the CAR-T product.3 Furthermore, 3 months after treatment, the 5 patients showed remission of SLE by DORIS criteria with a median Systemic Lupus Erythematosus Disease Activity Index score of 0 (range, 2). Reappearance of B-cells occurred at a mean of 110 days (SD, ±32 days) posttreatment with reappearing B-cells reported to be naïve and showing non–class-switched B-cell receptors. Patients continued to show drug-free remission at a median of 8 months of follow-up (range, 12).

In terms of safety, the product was reported to be well-tolerated. Cases of mild cytokine release syndrome were observed among the treated patients, but no cases of immune effector cell-associated neurotoxicity syndrome occurred. The study included 4 women and 1 man who had a median age of 22 years (range, 6). At enrollment, the patients had a median disease duration of 4 years (range, 8) and a median Systemic Lupus Erythematosus Disease Activity Index score of 16 (range, 8). Their disease was refractory to previous treatment with immunosuppressive drugs.

“The efficient clinical trial design was informed by the data package we submitted, including clinical safety data with the CABA-201 binder, our experience from prior autoimmune cell therapy IND applications, and our exclusive translational research partnership with the senior author of the Nature Medicine paper, which demonstrated 5/5 durable remissions throughout the follow-up period up to 17 months in patients with refractory SLE...” Steven Nichtberger, MD, the CEO and cofounder of Cabaletta Bio, said in a statement at the time of the IND clearance.2 “Based on its similarity to the product used in the Nature Medicine paper, we believe CABA-201 has the potential to provide deep and durable responses for patients with SLE and possibly other autoimmune diseases where B-cells play a role to initiate or sustain disease pathology. By achieving a timely IND clearance, we believe we are well positioned to generate 3-month clinical data on efficacy endpoints and tolerability for patients dosed with CABA-201 by the first half of 2024.”

1. Cabaletta Bio receives FDA fast track designation for CABA-201. News release. Cabaletta Bio, Inc. May 1, 2023. Accessed May 3, 2023.
2. Cabaletta Bio receives FDA clearance of IND application for CABA-201 for treatment of systemic lupus erythematosus. News release. Cabaletta Bio, Inc. March 31, 2023. Accessed May 3, 2023.
3. Mackensen A, Müller F, Mougiakakos D, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022;28(10):2124-2132. doi:10.1038/s41591-022-02017-5
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