On November 8, 2024 Autolus Therapeutics plc (Nasdaq: AUTL), an early-commercial stage biopharmaceutical company developing next-generation programmed T cell therapies, reported 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) (Press release, Autolus, NOV 8, 2024, View Source [SID1234648036]).
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"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 (OCR1) 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."
AUCATZYL will be manufactured at Autolus’ dedicated commercial manufacturing site, the Nucleus, in Stevenage, UK. The site was granted a Manufacturer’s Importation Authorization (MIA) and a GMP certificate from the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) in March 2024, and was inspected as part of the FDA approval process. No major or critical observations were identified by either the MHRA or FDA during the site inspections. The Nucleus will supply AUCATZYL globally, with Cardinal Health serving as Autolus’ commercial distribution partner in the U.S. Autolus will now engage with existing treatment centers to complete the onboarding process and initiate the first scheduling of patients to make AUCATZYL commercially available in the U.S.
ALL is an aggressive type of blood cancer that can also involve the lymph nodes, spleen, liver, central nervous system and other organs. Approximately 8,400 new cases of adult ALL are diagnosed every year in the US and EU, with around 3,000 patients in the relapsed refractory setting.1 Survival rates remain very poor in adult patients with r/r ALL, with median overall survival of eight months.2 In frontline treatment for adult r/r B-ALL, up to 50% of patients will ultimately relapse, and the standard-of-care treatment can trigger severe toxicities and may be burdensome for some patients.3,4
Marketing authorisation applications (MAAs) for obe-cel in adult r/r ALL are being reviewed by the regulators in both the EU and the UK, with a submission to the European Medicines Agency (EMA) accepted in March 2024, and a submission accepted by the UK MHRA in August 2024.
Conference Call
Management will host a conference call and webcast on November 11 at 8:30 am EST/1:30 pm BST to discuss the AUCATZYL approval. Conference call participants should pre-register using this link to receive the dial-in numbers and a personal PIN, which are required to access the conference call.
A simultaneous audio webcast and replay will be accessible on the events section of Autolus’ website.