FDA approves Aucatzyl (obecabtagene autoleucel) for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia – Autolus Therapeutics

Autolus Therapeutics plc  an early-commercial stage biopharmaceutical company developing next-generation programmed T cell therapies, announces the 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).

“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.”

Aucatzyl  was approved by the FDA based on results from the FELIX clinical trial of obe-cel in adult patients with r/r B-ALL. In the morphological disease cohort, 94 patients received at least one infusion of Aucatzyl of which 65 patients 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. In the efficacy evaluable patients (n=65), 63% achieved overall complete remission (OCR) which includes 51% of patients with CR at any time and 12% patients with CRi at any time. The major efficacy outcome was complete remission within 3 months, which was achieved in 42% patients, and the median duration of remission (DOR) was 14.1 months. Aucatzyl showed low levels of Cytokine Release Syndrome (CRS), with 3% Grade 3 events, and no Grade 4 or 5 events. Grade ≥ 3 Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) was reported in 7% of patients. No REMS was required by the FDA for Aucatzyl.

The safety of Aucatzyl includes a boxed warning for CRS, neurologic toxicities, and secondary hematological malignancies. ICANS, including fatal or life-threatening reactions, occurred in patients receiving Aucatzyl. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies. In the FELIX trial, the most common non-laboratory adverse reactions (incidence ≥ 20%) included CRS, infections-pathogen unspecified, musculoskeletal pain, viral infections, fever, nausea, bacterial infectious disorders, diarrhea, febrile neutropenia, ICANS, hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage.

“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, MD, PhD, FRCPath, 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.”

“We are so pleased to now be able to offer Aucatzyl, our first commercial product, to adult r/r B-ALL patients in the U.S. 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 Dr. Christian Itin, Chief Executive Officer of Autolus. “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.