FDA Accepts BLA for Obe-cel in Relapsed/Refractory B-Cell ALL

Developers originally submitted the BLA for obe-cel in relapsed/refractory B-cell ALL in November 2023.

The FDA has accepted a biologics license application (BLA) for obecabtagene autoleucel (obe-cel; AUTO1) as a treatment for adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL), according to a press release from Autolus Therapeutics.¹

The regulatory agency has set a Prescription Drug User Fee Act (PDUFA) date of November 16, 2024 for their decision on approving obe-cel in the aforementioned population.

Supporting data for the BLA came from the phase 1b/2 FELIX trial (NCT04404660) assessing obe-cel among those with relapsed/refractory ALL. According to data presented at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition, treatment with obe-cel elicited a complete response (CR) or CR with incomplete hematologic recovery (CRi) rate of 77% (n = 95/124) and a CR rate of 57% (n = 71/124).² Moreover, 96% of patients with evaluable minimal residual disease (MRD) status had MRD negativity based on central flow cytometry analysis.

Grade 3 or higher cytokine release syndrome (CRS) affected 2.4% of patients, and 7.1% had grade 3 or higher immune effector cell associated neurotoxicity syndrome (ICANS). Investigators reported that CAR T expansion was consistent across the phase 1b/2 cohorts, and that CAR T was persistent in most responders at the time of follow up.

“Acceptance of the BLA filing is an important milestone for Autolus and we look forward to continuing our collaboration with the FDA during the review cycle,” Christian Itin, PhD, chief executive officer at Autolus, said in the press release.¹ “With the PDUFA date set for November, we remain focused on preparing for the potential launch of obe-cel.”

In the FELIX study, patients underwent lymphodepletion with fludarabine at 4 x 30 mg/m² and cyclophosphamide at 2 x 500 mg/m². Additionally, investigators administered obe-cel at a target dose of 410 x 10⁶ CAR T cells as a split dose on days 1 and 10 as determined via pre-lymphodepletion bone marrow blast burden.

The trial’s primary end point was overall remission rate as assessed by independent review. Secondary end points included duration of remission, MRD-negative remission rate, safety, and CAR T expansion and persistence.

Patients 18 years and older with relapsed/refractory B-cell ALL and an ECOG performance status of 0 or 1 were able to enroll on the trial. Additional eligibility criteria included having adequate renal, hepatic, pulmonary, and cardiac function and documented CD19 positivity within 1 month prior to screening. Those with Philadelphia chromosome–positive ALL were eligible to enroll if they had intolerance to tyrosine kinase inhibitor (TKI) therapy, progressed on 2 lines of TKIs, or progressed on 1 line including a second-generation TKI.

Developers originally submitted the BLA for obe-cel in relapsed/refractory B-cell ALL in November 2023.³

“We are looking forward to continuing working with the FDA through the regulatory approval process. I would like to thank the treating physicians, patients, caregivers, and the dedicated team at Autolus for their support, trust, and commitment for the program to reach this important milestone,” Itin said in a press release at the time the BLA was submitted.³

References

1. Autolus Therapeutics announces acceptance of biologics license application for obecabtagene autoleucel (obe-cel) as a potential treatment for relapsed/refractory adult B-cell acute lymphoblastic leukemia (ALL). News release. Autolus Therapeutics. January 22, 2024. Accessed January 24, 2024. http://tinyurl.com/53s77653
2. Roddie C, Sandhu KS, Tholouli E, et al. Obecabtagene autoleucel (obe-cel, AUTO1) for relapsed/refractory adult B-cell acute lymphoblastic leukemia (R/R B-ALL): pooled analysis of the ongoing FELIX phase Ib/II study. Blood. 2023;142(suppl 1):222. doi:10.1182/blood-2023-179454
3. Autolus Therapeutics submits biologics license application to U.S. Food and Drug Administration for obecabtagene autoleucel (obe-cel) for patients with relapsed/refractory (r/r) adult B-cell acute lymphoblastic leukemia (ALL). News release. Autolus Therapeutics. November 27, 2023. Accessed January 24, 2024. https://shorturl.at/nzIJY