CHMP Recommends EU Approval of Obe-Cel for Relapsed/Refractory B-ALL

Chronic Lymphocytic Leukemia |

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The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of obecabtagene autoleucel (obe-cel; Aucatzyl) for the treatment of adult patients at least 26 years of age with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (B-ALL).¹

The recommendation is supported by data from the phase 1b/2 FELIX trial (NCT04404660). At a median follow-up of 21.5 months (range, 8.6-41.4), findings from FELIX published in the New England Journal of Medicine demonstrated that patients with relapsed/refractory B-ALL who received at least 1 infusion of obe-cel (n = 127) achieved an overall remission rate (ORR) of 77% (95% CI, 67%-85%), including a complete remission (CR) rate of 55%.² The median overall survival (OS) and event-free survival (EFS) were 15.6 months (95% CI, 12.9-not evaluable [NE]) and 11.9 months (95% CI, 8.0-22.1), respectively.

At a median follow-up of 20.3 months, patients in the pivotal cohort 2A (n = 94), which included those with morphologic disease at enrollment, achieved an ORR of 77% (95% CI, 67%-85%) with a CR rate of 55% (95% CI, 45%-66%). The median EFS was 9.0 months (95% CI, 6.1-15.0). The median duration of response was 14.1 months (95% CI, 8.2-NE).

“This positive CHMP opinion is a welcome advancement for physicians and patients in Europe, faced with treating adult [patients with] relapsed/refractory B-ALL with a poor prognosis, ”Claire Roddie, MD, PhD, FRCPath, lead Investigator of FELIX and an associate professor of hematology at the University College London Cancer Institute in England, stated in a news release.¹ “Obe-cel’s combination of favorable tolerability and potential long-term outcomes could offer an important new treatment option for patients in the European Union.”

In November 2024, the FDA approved obe-cel for the treatment of adult patients with relapsed/refractory B-ALL.³ The regulatory decision was also supported by data from FELIX.

FELIX enrolled patients who were at least 18 years old with relapsed/refractory CD19-positive B-cell ALL across 34 sites in Spain, the UK, and the US.² The study included patients with primary refractory disease; first relapse at 12 months or less; relapsed/refractory disease following at least 2 prior lines of systemic therapy; or relapsed/refractory disease following allogeneic transplant. Patients with CD19-positive, Philadelphia-positive B-ALL were eligible if they were intolerant to or had progressed on 2 lines of prior TKI therapy or 1 line of second-generation TKI therapy.

All patients underwent leukapheresis to allow for manufacturing of obe-cel, and bridging therapy was permitted at the investigator’s discretion. Patients received obe-cel via a bone-marrow burden–adjusted split dose after lymphodepletion, with bone marrow assessment mandated before lymphodepletion to guide the dose. A second dose was administered in the absence of severe or unresolved adverse effects.

The primary end point was ORR in cohort 2A. The key secondary end point was CR rate in cohort 2A. Additional secondary end points included OS, EFS, and safety.

In terms of safety, patients in the overall population experience any-grade cytokine release syndrome (CRS) at a rate of 68.5%; grade 3 or higher CRS was reported in 2.4% of patients. Any-grade Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 22.8% of patients; grade 3 or higher ICANS was reported in 7.1% of patients.

“This positive opinion from the CHMP highlights the significant unmet need and importance of effective treatment options for adult relapsed/refractory B-ALL," Christian Itin, CEO of Autolus, added in the news release.^{1 "}With FDA approval received in November 2024 and a UK Medicines and Healthcare products Regulatory Agency conditional marketing authorization received in April 2025, we are on our way to bringing this therapy to patients in need globally.”

References

1. Autolus Therapeutics announces positive CHMP opinion for obecabtagene autoleucel 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. May 23, 2025. Accessed May 23, 2025. https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-announces-positive-chmp-opinion
2. Roddie C, Sandhu KS, Tholouli E, et al. Obecabtagene autoleucel in adults with B-cell acute lymphoblastic leukemia. N Engl J Med. 2024;391(23):2219-2230. doi:10.1056/NEJMoa2406526
3. FDA approves obecabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. FDA. November 8, 2024. Accessed May 23, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-obecabtagene-autoleucel-adults-relapsed-or-refractory-b-cell-precursor-acute