Autolus Therapeutics Announces FDA Approval of AUCATZYL® (obecabtagene autoleucel – obe-cel) for adults with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL)
Autolus Therapeutics announces FDA approval of AUCATZYL® for treating adults with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). The approval is based on the FELIX clinical trial, where 63% of evaluable patients achieved overall complete remission, with 42% achieving complete remission within 3 months. The median duration of remission was 14.1 months. Notably, AUCATZYL is the first CAR T therapy approved without requiring a REMS program, showing low levels of Cytokine Release Syndrome (3% Grade 3) and manageable ICANS (7% Grade ≥3). The therapy will be manufactured at Autolus' Nucleus facility in Stevenage, UK, with Cardinal Health handling U.S. distribution.
Autolus Therapeutics annuncia l'approvazione da parte della FDA di AUCATZYL® per il trattamento degli adulti con leucemia linfoblastica acuta a cellule B recidivante/resistente (r/r B-ALL). L'approvazione si basa sul trial clinico FELIX, dove il 63% dei pazienti valutabili ha raggiunto una remissione completa complessiva, con il 42% che ha ottenuto una remissione completa entro 3 mesi. La durata mediana della remissione è stata di 14,1 mesi. È importante notare che AUCATZYL è la prima terapia CAR T approvata senza richiedere un programma REMS, mostrando bassi livelli di Sindrome da Rilascio di Citochine (3% Grado 3) e ICANS gestibili (7% Grado ≥3). La terapia sarà prodotta presso il centro Nucleus di Autolus a Stevenage, Regno Unito, con Cardinal Health che si occupa della distribuzione negli Stati Uniti.
Autolus Therapeutics anuncia la aprobación de la FDA de AUCATZYL® para el tratamiento de adultos con leucemia linfoblástica aguda de células B en recaída/refractaria (r/r B-ALL). La aprobación se basa en el ensayo clínico FELIX, donde el 63% de los pacientes evaluados logró una remisión completa general, con un 42% alcanzando la remisión completa en el plazo de 3 meses. La duración mediana de la remisión fue de 14,1 meses. Cabe destacar que AUCATZYL es la primera terapia CAR T aprobada sin necesidad de un programa REMS, mostrando bajos niveles de Síndrome de Liberación de Citoquinas (3% Grado 3) y ICANS manejables (7% Grado ≥3). La terapia se fabricará en la instalación Nucleus de Autolus en Stevenage, Reino Unido, y Cardinal Health se encargará de la distribución en EE. UU.
Autolus Therapeutics가 재발/불응성 B세포 급성 림프모구 백혈병(r/r B-ALL) 성인을 치료하기 위한 AUCATZYL®의 FDA 승인을 발표했습니다. 이번 승인은 FELIX 임상 시험에 기반하고 있으며, 평가 가능한 환자의 63%가 전반적인 완전 관해를 달성했으며, 42%는 3개월 이내에 완전 관해를 달성했습니다. 관해의 중앙 지속 기간은 14.1개월이었습니다. 특히, AUCATZYL은 REMS 프로그램 없이 승인된 첫 번째 CAR T 치료제로, 사이토카인 방출 증후군의 발생률이 낮습니다(3% 3등급) 그리고 관리 가능한 ICANS(7% 3등급 이상)가 보고되었습니다. 치료는 Autolus의 영국 스티븐이지에 있는 Nucleus 시설에서 제조되며, Cardinal Health가 미국 유통을 담당합니다.
Autolus Therapeutics annonce l'approbation par la FDA de AUCATZYL® pour le traitement des adultes atteints de leucémie aiguë lymphoblastique à cellules B en rechute/résistante (r/r B-ALL). L'approbation repose sur l'
Autolus Therapeutics kündigt die FDA-Zulassung von AUCATZYL® zur Behandlung von Erwachsenen mit rezidivierter/refraktärer B-Zell-akuter lymphoblastischer Leukämie (r/r B-ALL) an. Die Zulassung basiert auf der FELIX-Studie, in der 63 % der evaluierbaren Patienten eine vollständige Remission erreichten, wobei 42 % innerhalb von 3 Monaten eine vollständige Remission erzielten. Die mediane Remissionsdauer betrug 14,1 Monate. Bemerkenswert ist, dass AUCATZYL die erste CAR T-Therapie ist, die ohne ein REMS-Programm genehmigt wurde, mit niedrigen Raten von Cytokinfreisetzungssyndrom (3 % Grad 3) und handhabbaren ICANS (7 % Grad ≥3). Die Therapie wird in der Nucleus-Einrichtung von Autolus in Stevenage, UK, hergestellt, während Cardinal Health für die Distribution in den USA zuständig ist.
- First CAR T therapy approved without REMS requirement, indicating favorable safety profile
- High efficacy with 63% overall complete remission rate in evaluable patients
- Median duration of remission of 14.1 months
- Low Grade 3 CRS rate of 3% with no Grade 4 or 5 events
- Manufacturing facility already approved by MHRA and FDA with no major observations
- Safety concerns include boxed warning for CRS, neurologic toxicities, and secondary malignancies
- 7% of patients experienced Grade ≥3 ICANS
- Multiple common adverse reactions reported in ≥20% of patients
Insights
The FDA approval of AUCATZYL represents a significant breakthrough in treating relapsed/refractory B-ALL. The drug demonstrated impressive efficacy with
The therapy's manufacturing at Autolus' Nucleus facility in Stevenage, with successful MHRA and FDA inspections, ensures reliable production capacity. With approximately 3,000 patients in the relapsed/refractory setting across US and EU, AUCATZYL addresses a critical market need where current survival rates are poor (median 8 months).
This approval marks Autolus' transition to a commercial-stage company, opening up a significant revenue stream in the lucrative CAR T therapy market. With a market cap of
The therapy's superior safety profile could lead to broader adoption and potentially lower treatment costs compared to other CAR T therapies requiring REMS programs. Pending approvals in the EU and UK markets would further expand the commercial opportunity.
- AUCATZYL is the first CAR T therapy approved by the FDA with no requirement for a REMS program (Risk Evaluation Mitigation Strategy)
- Approval based on FELIX clinical trial of obe-cel in adult patients with r/r B-ALL
- Conference call to be held on November 11 at 08:30 am EST/13:30 pm BST: conference call participants should pre-register using the link at the bottom of this press release
LONDON, Nov. 08, 2024 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc (Nasdaq: AUTL), an early-commercial stage biopharmaceutical company developing next-generation programmed T cell therapies, today announces 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).
“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 >
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 ≥
“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
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.
About Autolus Therapeutics plc
Autolus is a biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer and autoimmune disease. Using a broad suite of proprietary and modular T cell programming technologies, Autolus is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize target cells, break down their defense mechanisms and eliminate these cells. Autolus has an FDA approved product, AUCATZYL, and a pipeline of product candidates in development for the treatment of hematological malignancies, solid tumors and autoimmune diseases. For more information, please visit www.autolus.com
About AUCATZYL® (obecabtagene autoleucel, obe-cel, AUTO1)
AUCATZYL is a B-lymphocyte antigen CD19 (CD19) chimeric antigen receptor (CAR) T cell therapy designed to overcome the limitations in clinical activity and safety compared to current CD19 CAR T cell therapies. AUCATZYL is designed with a fast target binding off-rate to minimize excessive activation of the programmed T cells. AUCATZYL was approved by the FDA for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia on November 16, 2024. In the EU a regulatory submission to the EMA was accepted in April 2024, while in the UK, an MAA was submitted to MHRA in July 2024.
INDICATION
AUCATZYL® is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, and SECONDARY HEMATOLOGICAL MALIGNANCIES
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WARNINGS AND PRECAUTIONS
Cytokine Release Syndrome (CRS)
Cytokine Release Syndrome (CRS) occurred following treatment with AUCATZYL. CRS was reported in
Prior to administering AUCATZYL, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage CRS. During and following treatment with AUCATZYL, closely monitor patients for signs and symptoms of CRS daily for at least 14 days at the healthcare facility following the first infusion. Continue to monitor patients for CRS for at least 4 weeks following each infusion with AUCATZYL. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, immediately evaluate the patient for hospitalization and institute treatment with supportive care based on severity and consider further management per current practice guidelines.
Neurologic Toxicities
Neurologic toxicities including Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), which were fatal or life-threatening, occurred following treatment with AUCATZYL. Neurologic toxicities were reported in
Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS)
ICANS events occurred in
The median time to onset for ICANS events after the first infusion was 8 days (range: 1 to 10 days) and 6.5 days (range: 2 to 22 days) after the second infusion, with a median duration of 8.5 days (range: 1 to 53 days).
Eighty-eight percent (21/24) of patients received treatment for ICANS. All treated patients received high-dose corticosteroids and
Counsel patients to seek medical attention should signs or symptoms of neurologic toxicity/ ICANS occur. At the first sign of Neurologic Toxicity /ICANS, immediately evaluate patients for hospitalization and institute treatment with supportive care based on severity and consider further management per current practice guidelines.
Effect on Ability to Drive and Use Machines
Due to the potential for neurologic events, including altered mental status or seizures, patients receiving AUCATZYL are at risk for altered or decreased consciousness or coordination in the eight weeks following AUCATZYL infusion or until resolution of the neurological event by the treating physician. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.
Prolonged Cytopenias
Patients may exhibit cytopenias including anemia, neutropenia, and thrombocytopenia for several weeks after treatment with lymphodepleting chemotherapy and AUCATZYL. In patients who were responders to AUCATZYL, Grade ≥ 3 cytopenias that persisted beyond Day 30 following AUCATZYL infusion were observed in
Infections
Severe, including life-threatening and fatal infections occurred in patients after AUCATZYL infusion. Non-COVID-19 infections of all grades occurred in
Grade 3 or higher febrile neutropenia was observed in
Viral reactivation, potentially severe or life-threatening, can occur in patients treated with drugs directed against B cells. There is no experience with manufacturing AUCATZYL for patients with a positive test for human immunodeficiency virus (HIV) or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV). Perform screening for HBV, HCV and HIV in accordance with clinical guidelines before collection of cells for manufacturing.
Hypogammaglobulinemia
Hypogammaglobulinemia and B-cell aplasia can occur in patients after AUCATZYL infusion. Hypogammaglobulinemia was reported in
Immunoglobulin levels should be monitored after treatment with AUCATZYL and managed per institutional guidelines including infection precautions, antibiotic or antiviral prophylaxis, and immunoglobulin replacement.
The safety of immunization with live viral vaccines during or following treatment with AUCATZYL has not been studied. Vaccination with live viral vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy treatment, during AUCATZYL treatment, and until immune recovery following treatment with AUCATZYL.
Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS)
HLH/MAS including fatal and life-threatening reactions occurred after treatment with AUCATZYL. HLH/MAS was reported in
Hypersensitivity Reactions
Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO), an excipient used in AUCATZYL. Observe patients for hypersensitivity reactions during and after AUCATZYL infusion.
Secondary Malignancies
Patients treated with AUCATZYL may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Autolus at 1-855-288-5227 for reporting and to obtain instructions on the collection of patient samples for testing.
Adverse Reactions
The safety of AUCATZYL was evaluated in the FELIX study in which 100 patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) received AUCATZYL at a median dose of 410 × 106 CD19 CAR-positive viable T cells (range: 10 to 480 × 106 CD19 CAR-positive viable T cells with
The most common serious adverse reactions of any Grade (incidence ≥
Please see full Prescribing Information, including BOXED WARNING and Medication Guide.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to: statements regarding the market and therapeutic potential of for AUCATZYL for adult r/r B-ALL; Autolus’ development and commercialization of its product candidates; the expected clinical benefits of AUCATZYL; Autolus’ manufacturing, sales and marketing plans for AUCATZYL, including expectations regarding the timing of commercial launch in the United States and the ability to reach patients in a timely manner; the amount and timing of milestone payments under Autolus’ collaboration and license agreements; and future development plans of AUCATZYL, including the timing or likelihood of expansion into additional markets or geographies and related regulatory approvals. Any forward-looking statements are based on management's current views and assumptions and involve risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in such statements. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation: Autolus’ ability to maintain regulatory approval of AUCATZYL; its ability to execute its commercialization strategy for AUCATZYL; its ability to develop, manufacture and commercialize its other product candidates and the timing or likelihood of expansion of AUCATZYL into additional markets or geographies; Autolus’ ability to establish and expand a commercial infrastructure and to successfully launch, market and sell AUCATZYL; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or future regulatory approval; the labelling for AUCATZYL/obe-cel in any future indication or patient population, if approved; the potential for payors to delay, limit or deny coverage for AUCATZYL; Autolus’ ability to obtain, maintain and enforce intellectual property protection for AUCATZYL or any product candidates it is developing; the results of clinical trials are not always being predictive of future results; the cost, timing and results of clinical trials; that many product candidates do not become approved drugs on a timely or cost effective basis or at all; the ability to enroll patients in clinical trials; and possible safety and efficacy concerns. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Autolus’ actual results to differ from those contained in the forward-looking statements, see the section titled "Risk Factors" in Autolus' Annual Report on Form 10-K filed with the Securities and Exchange Commission, or the SEC, on March 21, 2024 as well as discussions of potential risks, uncertainties, and other important factors in Autolus' subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Autolus undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law. You should, therefore, not rely on these forward-looking statements as representing Autolus’ views as of any date subsequent to the date of this press release.
Contact:
Olivia Manser
+44 (0) 7780 471 568
o.manser@autolus.com
Julia Wilson
+44 (0) 7818 430877
j.wilson@autolus.com
Susan A. Noonan
S.A. Noonan Communications
+1-917-513-5303
susan@sanoonan.com
References
1. SEER and EUCAN estimates for US and EU respectively
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894150/
3. Aureli A, Marziani B, Venditti A, Sconocchia T, Sconocchia G. Acute lymphoblastic leukemia immunotherapy treatment: now, next, and beyond. Cancers (Basel). 2023;15:3346.
4. Dhakal P, Kaur J, Gundabolu K, Bhatt VR. Immunotherapeutic options for management of relapsed or refractory B-cell acute lymphoblastic leukemia: how to select newly approved agents? Leuk Lymphoma. 2020;61:7-17.
11/24 US-AUC-0082
*Rate of Overall Complete Remission “At Anytime” includes Complete Remission (CR) and Complete Remission with incomplete hematologic recovery (CRi) “At Anytime”
FAQ
What is the FDA-approved indication for AUCATZYL (AUTL)?
What was the complete remission rate in the FELIX trial for AUCATZYL (AUTL)?
What are the main safety concerns with AUCATZYL (AUTL)?
Where will AUCATZYL (AUTL) be manufactured?
