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FDA Approves Autolus' AUCATZYL for Relapsed/Refractory B-cell ALL

8 months ago4 min read

Key Insights

  • The FDA has approved AUCATZYL (obecabtagene autoleucel) for adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

  • AUCATZYL is a CD19-directed CAR T-cell therapy designed to minimize excessive T-cell activation, offering a novel approach to treating this aggressive cancer.

  • The approval was based on the FELIX clinical trial, which demonstrated a 63% overall complete remission rate in efficacy-evaluable patients.

Autolus Therapeutics plc (Nasdaq: AUTL) announced that the U.S. Food and Drug Administration (FDA) has granted marketing approval for AUCATZYL® (obecabtagene autoleucel) for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r B-ALL). This marks a significant advancement in the treatment landscape for this aggressive cancer, addressing a critical unmet need for patients who have exhausted other treatment options.

Clinical Efficacy and Safety

The FDA's decision was primarily based on the results of the pivotal FELIX clinical trial, which evaluated the efficacy and safety of AUCATZYL in adult patients with r/r B-ALL. The study demonstrated compelling clinical outcomes, with 63% of efficacy-evaluable patients (n=65) achieving overall complete remission (OCR). This OCR rate included 51% of patients achieving complete remission (CR) and 12% achieving complete remission with incomplete hematological recovery (CRi). A key efficacy outcome was complete remission within 3 months, achieved in 42% of patients, with a median duration of remission (DOR) of 14.1 months.
AUCATZYL also demonstrated a favorable safety profile in the FELIX trial. The incidence of Cytokine Release Syndrome (CRS) was low, with only 3% of patients experiencing Grade 3 events and no Grade 4 or 5 events reported. Grade ≥ 3 Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) was observed in 7% of patients. Importantly, the FDA did not require a REMS program for AUCATZYL, highlighting its manageable safety profile.

Mechanism of Action and Design

AUCATZYL is a CD19-directed genetically modified autologous T-cell immunotherapy. It is designed to overcome limitations associated with existing CD19 CAR T-cell therapies by incorporating a fast target binding off-rate. This design aims to minimize excessive activation of programmed T-cells, potentially reducing the risk of severe toxicities while maintaining potent anti-tumor activity.

Expert Commentary

"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, U.S. lead investigator of the FELIX study and professor of Leukemia, ALL Section Chief, at The University of Texas MD Anderson Cancer Center, Houston, Texas. "This milestone approval, based on the demonstrated clinical benefit of AUCATZYL, brings new hope for adult patients with relapsed/refractory B-ALL."
Dr. Claire Roddie, MD, PhD, FRCPath, Lead investigator of the FELIX study and Associate Professor of Haematology at the University College London (UCL) Cancer Institute, added, "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. 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."

Manufacturing and Availability

AUCATZYL will be manufactured at Autolus’ dedicated commercial manufacturing site, the Nucleus, in Stevenage, UK. The facility has received the necessary authorizations and certifications from regulatory agencies, including the MHRA in the UK and the FDA in the US. Autolus is partnering with Cardinal Health for commercial distribution in the U.S. and will begin onboarding existing treatment centers to make AUCATZYL commercially available.

Disease Burden and Unmet Need

Acute lymphoblastic leukemia (ALL) is an aggressive blood cancer affecting both adults and children. Approximately 8,400 new cases of adult ALL are diagnosed annually in the US and EU, with about 3,000 patients experiencing relapse or refractory disease. Survival rates for adult patients with r/r ALL remain poor, with a median overall survival of approximately eight months. Current standard-of-care treatments can be associated with severe toxicities, highlighting the need for more effective and better-tolerated therapies.

Ongoing Regulatory Reviews

Marketing authorization applications (MAAs) for obe-cel in adult r/r ALL are currently under review by regulatory authorities in both the EU and the UK. The European Medicines Agency (EMA) accepted the submission in March 2024, and the UK MHRA accepted the submission in August 2024.
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