FDA Approves Autolus’ Aucatzyl for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia

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The FDA has approved Autolus Therapeutics’ Aucatzyl (obecabtagene autoleucel or obe-cel), a chimeric antigen receptor T-cell therapy for adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). According to the company, approval was based on promising results from the FELIX trial.¹

“Adult ALL is an extremely aggressive cancer, and there is a high unmet medical need that exists in the treatment of patients with this disease once they relapse, where historically they suffer from poor outcomes,” said Elias Jabbour, MD, US lead investigator, FELIX study, professor of leukemia, ALL section chief, The University of Texas MD Anderson Cancer Center, Houston, Texas, in a press release.“This milestone approval, based on the demonstrated clinical benefit of Aucatyzl, brings new hope for adult patients with relapsed/refractory B-ALL.”

FELIX was an open-label, multi-center, global, single-arm Phase Ib/II study.2 The morphological disease cohort consisted of 94 patients, who received at least one infusion of Aucatzyl. Additionally, 65 patients in the group had > 5% blasts in the bone marrow after screening and prior to the start of lymphodepletion therapy and received a conforming product, qualifying them as efficacy evaluable. The primary endpoint of the study was overall remission rate (ORR) defined as proportion of patients achieving complete response by central assessment.²

Results found that in the 65 efficacy evaluable patients, 63% demonstrated overall complete remission (OCR)1, with 42% achieving CR within three months and a median remission duration of 14.1 months.

Aucatzyl demonstrated favorable safety data, with low rates of severe cytokine release syndrome and a 7% incidence of grade ≥ 3 immune effector cell-associated neurotoxicity syndrome. Other adverse events included infections-pathogen unspecified, musculoskeletal pain, viral infections, fever, nausea, bacterial infectious disorders, diarrhea, febrile neutropenia, hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage.¹

“Based on the experience in the FELIX trial Aucatzyl is highly active and can be well managed, offering an attractive risk benefit profile for B-ALL patients,” said Claire Roddie, MD, PhD, FRCPath, lead investigator, FELIX study, associate professor, hematology, University College London Cancer Institute, in the press release. “In the FELIX trial Aucatzyl has shown long term persistence and deep responses which we believe are critical for long term remissions in B-ALL.”

An estimated 8,400 new cases of adult ALL are diagnosed every year in the United States and EU, with approximately 3,000 patients in the relapsed refractory setting. Currently, the median overall survival is eight months.¹

“We are so pleased to now be able to offer Aucatzyl, our first commercial product, to adult r/r B-ALL patients in the US. This approval would not have been possible without the support of all the patients, their families and caregivers, their treating physicians and the nurses and investigators at the treatment centers—thank you,” said Christian Itin, CEO, Autolus, in the press release. “This milestone is the culmination of many years of hard work, the foundational work by our partners at UCL and the unwavering commitment of our internal team, our external partners and shareholders. This is a proud day for Autolus.”

Autolus stated that the treatment will be manufactured at its dedicated commercial manufacturing site, the Nucleus, in Stevenage, UK. Back in March, the site was granted a Manufacturer’s Importation Authorization and a Good Manufacturing Practice certificate from the Medicines and Healthcare products Regulatory Agency. Moving forward, the company is expected to engage with existing treatment centers to complete the onboarding process and initiate commercial availability in the United States.¹

References

1. 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). Autolus. November 8, 2024. Accessed November 12, 2024. https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-announces-fda-approval-aucatzylr

2. Safety and efficacy of obecabtagene autoleucel (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. ASCO. Accessed November 12, 2024. https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.7000