FDA grants RMAT designation to CRISPR-edited CAR-T for advanced B-cell malignancies
The FDA granted regenerative medicine advanced therapy designation to CTX110, a chimeric antigen receptor T-cell therapy in development for treatment of relapsed or refractory B-cell malignancies.
CTX110 (CRISPR Therapeutics) is an allogeneic, CD19-targeted, CRISPR/Cas9 gene-edited CAR T-cell therapy designed to treat adults with CD19-positive B-cell malignancies, including non-Hodgkin lymphoma, B-cell lymphoma and B-cell acute lymphoblastic leukemia.
The FDA based the regenerative medicine advanced therapy (RMAT) designation on results of the ongoing phase 1, open-label, multicenter CARBON trial. The dose-escalation study is designed to assess the safety and efficacy of the therapy for adults with relapsed or refractory CD19-positive B-cell malignancies who received at least two previous lines of therapy.
Patients completed a 3-day course of lymphodepletion, then received IV infusions of CTX110 at one of five dose levels — 30 × 106 CAR T cells (dose level 1, n = 3), 100 × 106 CAR T cells (dose level 2, n = 3), 300 × 106 CAR T cells (dose level 3, n = 6), 450 × 106 CAR T cells (dose level 3.5, n = 6) or 600 × 106 CAR T cells (dose level 4, n = 8).
Topline data released by the manufacturer in October showed a 58% overall response rate for dose levels 2, 3 and 4 on an intent-to-treat basis, with a 38% complete response rate among these patients. The therapy exhibited a favorable safety profile, and four of nine patients who achieved complete response by day 28 remained in remission at 6 months after therapy.
“This RMAT designation is based on the encouraging clinical data we have presented thus far, and it is an important milestone that recognizes the transformative potential of CTX110 for the treatment of [hematologic] malignancies,” Samarth Kulkarni, PhD, CEO of CRISPR Therapeutics, said in a company-issued press release. “We look forward to working closely with the FDA as we continue our efforts to bring this important new therapeutic modality to patients.”
The FDA’s RMAT designation program, part of the 21st Century Cures Act, is designed to expedite review of regenerative medicine therapies intended to treat, modify, reverse or cure serious or life-threatening diseases or conditions. Preliminary clinical evidence must indicate the therapy has the potential to address unmet medical needs.