The U.S. Food and Drug Administration (FDA) has granted marketing approval to 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 landscape for this aggressive cancer, addressing a critical unmet need for patients who have exhausted other treatment options. The approval was announced by Autolus Therapeutics plc, the biopharmaceutical company developing the next-generation programmed T-cell therapies. Aucatzyl is a CD19-directed CAR T-cell therapy designed to overcome limitations in clinical activity and safety compared to current CD19 CAR T-cell therapies.
Efficacy and Safety Data from the FELIX Trial
The FDA's decision was based on the results of the pivotal FELIX clinical trial, which evaluated the efficacy and safety of obecabtagene autoleucel (obe-cel) in adult patients with r/r B-ALL. The study demonstrated promising outcomes, with 63% of efficacy-evaluable patients (n=65) achieving overall complete remission (OCR), including 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, indicating a sustained treatment effect. The major efficacy outcome was complete remission within 3 months, which was achieved in 42% patients.
Dr. 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, stated, "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. This milestone approval, based on the demonstrated clinical benefit of Aucatzyl, brings new hope for adult patients with relapsed/refractory B-ALL."
In terms of safety, Aucatzyl demonstrated a manageable profile. Cytokine Release Syndrome (CRS) was observed, with 3% of patients experiencing Grade 3 events and no Grade 4 or 5 events. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) of Grade ≥ 3 was reported in 7% of patients. The FDA did not require a Risk Evaluation and Mitigation Strategy (REMS) for Aucatzyl, reflecting confidence in its safety management.
Mechanism of Action and Design
Aucatzyl is designed with a fast target binding off-rate to minimize excessive activation of the programmed T cells. This innovative design aims to enhance the therapy's safety and efficacy, providing a more favorable risk-benefit profile for patients. The therapy is administered as a single infusion of genetically modified autologous T cells, following lymphodepletion.
Manufacturing and Distribution
Aucatzyl will be manufactured at Autolus’ dedicated commercial manufacturing site, the Nucleus, in Stevenage, UK. The facility has received 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 timely access to the therapy for patients in need.
Disease Burden and Unmet Need
Acute lymphoblastic leukemia (ALL) is an aggressive blood cancer that affects approximately 8,400 new adults each year in the US and EU, with about 3,000 patients in the relapsed/refractory setting. Despite advancements in treatment, survival rates remain poor for adult patients with r/r B-ALL, with a median overall survival of approximately eight months. Current standard-of-care treatments can be burdensome and trigger severe toxicities, highlighting the urgent 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 regulatory authorities in 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. These reviews could potentially expand the availability of Aucatzyl to patients in these regions.
Safety Information
The safety profile of Aucatzyl includes a boxed warning for CRS, neurologic toxicities, and secondary hematological malignancies. Common adverse reactions (incidence ≥ 20%) include CRS, infections, musculoskeletal pain, viral infections, fever, nausea, bacterial infectious disorders, diarrhea, febrile neutropenia, ICANS, hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage. Healthcare providers should monitor patients closely for signs and symptoms of these adverse reactions and manage them promptly according to established guidelines.
