European Commission Approves Obe-Cel for Adults With R/R B-Cell Precursor Acute Lymphoblastic Leukemia

Claire Roddie, MD, PhD, FRCPath

The European Commission (EC) has granted marketing authorization to obecabtagene autoleucel (Aucatzyl; Autolus Inc), also known as obe-cel, a CD19-directed genetically modified autologous T-cell immunotherapy, for the treatment of adults aged 26 years and older with relapsed or refractory (r/r) B-cell precursor acute lymphoblastic leukemia (B-ALL).¹

The therapy was approved based on the findings of the pivotal phase 1b/2 FELIX clinical trial (NCT04404660), which evaluated the therapy in adult patients with r/r B-ALL. Results from FELIX were published in the New England Journal of Medicine in November of last year showing a complete response (CR) rate/CR with incomplete hematological recovery rate (CRi) of 76.6% for patients in the pivotal cohort (n = 94) who were treated with obe-cel. Furthermore, it was reported that the median duration of response in the study for all patients who received obe-cel was 21.2 months and that the median event-free survival (EFS) was 11.9 months. The estimated 6-month EFS rate constituted 65.4% and the estimated 12-month EFS rate was found to be 49.5%.

With regard to safety, cases of cytokine release syndrome (CRS) occurred in 68.5% of patients (87 of 127). CRS cases assessed as grade 3 or higher occurred in 2.4% of patients (3 of 127). Cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in 22.8% of patients (29 of 127) and grade 3 or higher ICANS cases were reported in 7% of patients (9 of 127). The most common nonlaboratory adverse events assessed as grade 3 or higher included infections (unspecified pathogen, occurred in 32% of patients), febrile neutropenia (24%), and bacterial infectious disorders (11%).

“We believe Aucatzyl represents an important new treatment option for physicians treating adult r/r B-ALL patients,” Christian Itin, PhD, the chief executive officer of Autolus, said in a statement.¹ “With the EU marketing authorization, we are now evaluating market entry opportunities in EU countries.”

The EC’s approval applies to the 27 member states of the EU, as well as Iceland, Norway and Liechtenstein. Notably, obe-cel has been approved in the United States since late 2024.^2,3 The FDA’s approved indication differs slightly from the EC’s. In the United States, the therapy is approved for adults with r/r B-cell precursor acute lymphoblastic leukemia ALL, without the stipulation that the patients must be 26 years of age or older. The agency's total recommended dose of obe-cel is 410×10⁶ CD19 chimeric antigen receptor (CAR)-positive viable T-cells, preceded by fludarabine and cyclophosphamide lymphodepleting chemotherapy and administered as split-dose infusion on Day 1 and Day 10 (±2 days) of treatment, based on bone marrow blast assessment. Risk Evaluation and Mitigation Strategies (REMS) were not required by the agency at the time of approval. Obe-cel has also previously been approved in the United Kingdom by the Medicines and Healthcare products Regulatory Agency.

Obe-cel incorporates a novel fast off-rate CD19 binding domain intended to shorten the time that it takes for CAR T-cells bind to leukemia cells, which may simultaneously decrease the number of cytokines secreted and reduce the rate of T-cell exhaustion.⁴ CGTLive®'s sister site OncLive® spoke with Claire Roddie, MD, PhD, FRCPath, the lead investigator of the FELIX study and Associate Professor of Haematology at the University College London (UCL) Cancer Institute, about obe-cel in June 2023.

“...We know that other products on the market for adult ALL have got significant toxicity profiles and that's actually really difficult for us physicians to manage and particularly difficult for the patients and their families,” Roddie told OncLive. “It makes it difficult to anticipate or imagine a clinical world where we can give these comfortably as outpatient therapies, which is obviously where [we want to go]—we want to be able to improve the patient experience, quality of life, etc. And so, I think that's where obe-cel comes into this because the toxicity profile is so much less difficult for patients to tolerate—even patients with lots and lots of disease—and I think that's its biggest selling point. From the perspective of just safely navigating patients through this therapy, it’s much more straightforward.”

REFERENCES
1. AutolusTherapeutics’ CAR T therapy AUCATZYL® (obecabtageneautoleucel) granted European Marketing Authorization for adult patients (age 26 and older) with relapsed or refractory b-cell precursor acute lymphoblastic leukemia (R/R B-ALL). News release. Autolus Therapeutics plc. July 21, 2025. Accessed July 24, 2025. https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-car-t-therapy-aucatzylr-obecabtagene
2. FDA approves obecabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. News release. FDA. November 8, 2024. Accessed July 24, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-obecabtagene-autoleucel-adults-relapsed-or-refractory-b-cell-precursor-acute
3. Autolus Therapeutics Announces FDA Approval of AUCATZYL® (obecabtagene autoleucel – obe-cel) for adults with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). News release. Autolus Therapeutics. November 8, 2024. Accessed July 24, 2025. https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-announces-fda-approval-aucatzylr
4. Roddie C, Sandhu KS, Tholouli E, et al. Safety and efficacy ofobecabtageneautoleucel (obe-cel, AUTO1), a fast-off rate CD19 CAR, in relapsed/refractory adult B-cell acute lymphoblastic leukemia (r/r B-ALL): Top line results of the pivotal FELIX study. Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #7000