Obe-Cel Granted RMAT Designation in R/R B-Acute Lymphocytic Leukemia

The US FDA has granted regenerative medicine advanced therapy (RMAT) to Autolus Therapeutics’ investigational gene-edited cell therapy, obecabatagene autoleucel (obe-cel). The autologous CD19-directed CAR T-cell therapy is currently being evaluated in the phase 2 FELIX clinical trial in patients with relapsed or refractory B-acute lymphocytic leukemia (B-ALL).¹

The RMAT designation will help expedite the development and review of the investigational therapy, which has previously been granted priority medicines (PRIME) designation by the European Medicines Agency for B-ALL and orphan medical product designation for acute lymphoblastic leukemia,² and innovative licensing and access pathway by the Medicines and Healthcare products Regulatory Agency of the United Kingdom.

“RMAT designation is an important regulatory milestone for obe-cel and highlights its potential to address the unmet medical need for adult patients with relapsed and refractory B-ALL,” said Christian Itin, chief executive officer of Autolus, in a statement. “RMAT designation from FDA, PRIME designation from EMA, and ILAP designation from MHRA facilitate regulatory interactions with key health authorities and supports our drive to bring this innovative therapy to patients as quickly as possible.”

Obe-cel unique CAR design helps to minimize the excessive activation of T cells, in turn potentially reducing toxicities like cytokine release syndrome and T-cell exhaustion which may help improve cell persistence and target engagement.

The ongoing phase 1b/2 FELIX trial (NCT04404660) has a target enrollment of 140 patients with R/R B-ALL across centers in the US, Europe, and United Kingdom. The primary end point is overall response rate, with secondary end points that include response duration, minimum residual disease negative complete response rate, and safety.

In addition to the FELIX trial, obe-cel is also currently being evaluated in a phase 1 clinical trial in B-cell non-Hodgkin lymphoma, in partnership with University College London.

The feasibility and safety of the novel second-generation CD19-CAR was demonstrated in the phase 1 ALLCAR19 trial (NCT02935257), during which 85% of the 20 patients who received infusion of the cell therapy achieved minimal residual disease-negative complete response at month 1.³ Event-free survival was 68.3% at 6 months and 48.3% and 12 months, with ongoing cell expansion and durable CAR-T persistence observed in 15 of 20 patients at last follow-up. No reports of grade 3 or higher cytokine release syndrome were recorded, and 15% of patients experienced grade 3 neurotoxicity that resolved to grade 1 or less within 72 hours of steroid treatment.

REFERENCES

1. FDA grants regenerative medicine advanced therapy (RMAT) designation to Autolus’ CAR T cell therapy, obe-cel, for the treatment of adult B-ALL. News release. Autolus Therapeutics. April 25, 2022. https://www.biospace.com/article/releases/fda-grants-regenerative-medicine-advanced-therapy-rmat-designation-to-autolus-car-t-cell-therapy-obe-cel-for-the-treatment-of-adult-b-all/

2. Autolus Therapeutics receives EMA orphan medical product designation for obe-cel for treatment of acute lymphoblastic leukemia. News release. Autolus Therapeutics. March 31, 2022. https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-receives-ema-orphan-medical-product

3. Roddie C, Dias J, O’Reilly MA, et al. Durable responses and low toxicity after fast off-rate cd19 chimeric antigen receptor-t therapy in adults with relapsed or refractory b-cell acute lymphoblastic leukemia. J Clin Oncol. 2021;39(30):3352-3363. doi:10.1200/JCO.21.00917