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 approval marks a significant advancement in the treatment of this aggressive cancer, addressing a critical unmet need for patients who have relapsed after initial therapies.
The approval of AUCATZYL was based on the results of the pivotal FELIX clinical trial. The study demonstrated a high rate of overall complete remission (OCR) in patients treated with the CAR T-cell therapy. Specifically, in the efficacy-evaluable patients (n=65), 63% achieved OCR, which included 51% with complete remission (CR) and 12% with complete remission with incomplete hematologic recovery (CRi). The median duration of remission (DOR) was 14.1 months. A key efficacy outcome was complete remission within 3 months, achieved in 42% of patients.
Clinical Efficacy and Safety Profile
The FELIX trial results highlighted the manageable safety profile of AUCATZYL. Cytokine Release Syndrome (CRS) was observed at low levels, with only 3% of patients experiencing Grade 3 events, and no Grade 4 or 5 events reported. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) of Grade ≥ 3 was reported in 7% of patients. Notably, the FDA did not require a REMS program for AUCATZYL, underscoring its favorable risk-benefit profile.
"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 Dr. Elias Jabbour, 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."
Manufacturing and Commercialization
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 both the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) and the FDA. Cardinal Health will serve as Autolus’ commercial distribution partner in the U.S., ensuring the therapy reaches patients efficiently.
Disease Burden and Current Treatment Landscape
Approximately 8,400 new cases of adult ALL are diagnosed annually in the US and EU, with about 3,000 patients in the relapsed/refractory setting. The survival rates for these patients remain poor, with a median overall survival of approximately eight months. Current standard-of-care treatments can trigger severe toxicities and may be burdensome for some patients, highlighting the need for more effective and tolerable therapies.
Ongoing Regulatory Reviews
Marketing authorization applications (MAAs) for obe-cel in adult r/r ALL are currently under review by regulators 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.
Safety Information
The safety information for AUCATZYL includes a boxed warning for Cytokine Release Syndrome (CRS), neurologic toxicities, and secondary hematological malignancies. Common adverse reactions (incidence ≥ 20%) included CRS, infections, musculoskeletal pain, viral infections, fever, nausea, bacterial infectious disorders, diarrhea, febrile neutropenia, ICANS, hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage. Patients should be monitored closely for signs and symptoms of these adverse reactions, and appropriate management strategies should be implemented.
"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 Dr. Claire Roddie, Lead investigator of the FELIX study and Associate Professor of Haematology at the University College London (UCL) Cancer Institute. "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."
