Save up to 80% by drug discount in your pharmacy with "Pharmacy Near Me - National Drug Discount Card"
You can scan QR Code(just open camera on your phone/scan by application) from the image on prescription drug discount card to save it to your mobile phone. Or just click on image if you're on mobile phone.
| Product NDC Code | 83047-410 | ||||
|---|---|---|---|---|---|
| Drug Name | Aucatzyl |
||||
| Type | Brand | ||||
| Dosage Form | KIT | ||||
| RxCUI drug identifier | 2700168, 2700173, 2700174, 2700175 |
||||
| Application Number | BLA125813 | ||||
| Labeler Name | Autolus Inc. | ||||
| Packages |
|
||||
| Check if available Online | Get Medication Prices online with Discount |
Overdosage of AUCATZYL
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.10 OVERDOSAGE In FELIX Study (all cohorts N=127), occurrences of overdose were observed at the administration of the first dose in 4% (5/127) of patients. All 5 patients had bone marrow blasts > 20% and should have received a first dose of 10 × 10 6 CAR-positive viable T cells but instead received a higher dose between 68 and 103 × 10 6 CAR-positive viable T cells. CRS, ICANS and HLH, including severe events, were observed in patients who received overdose of AUCATZYL. In the event of a suspected overdose, closely monitor patients for any adverse reactions and administer treatment according to institutional practice and treatment guidelines .
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6 ADVERSE REACTIONS The most common (non-laboratory) adverse reactions (incidence ≥ 20%) are: CRS, infections - pathogen unspecified, musculoskeletal pain, viral infections, fever, nausea, bacterial infectious disorders, diarrhea, febrile neutropenia, ICANS, hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Autolus Inc at toll-free phone 1-855-288-5227 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch ( 17 ). 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. 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 × 10 6 CD19 CAR-positive viable T cells (range: 10 to 480 × 10 6 CD19 CAR-positive viable T cells with 90% of patients receiving the recommended dose of 410 × 10 6 +/- 25%). [see Clinical Studies (14) ]. The most common serious adverse reactions of any Grade (incidence ≥ 2%) included infections-pathogen unspecified, febrile neutropenia, ICANS, CRS, fever, bacterial infectious disorders, encephalopathy, fungal infections, hemorrhage, respiratory failure, hypotension, ascites, HLH/MAS, thrombosis and hypoxia. Nine patients (9%) experienced fatal adverse reactions which included infections (sepsis, pneumonia, peritonitis), ascites, pulmonary embolism, acute respiratory distress syndrome, HLH/MAS and ICANS. Of the 9 patients, five patients who died from infections had pre-existing and ongoing neutropenia prior to receiving bridging therapy, lymphodepletion chemotherapy treatment and/or AUCATZYL. Table 3 summarizes the adverse reactions (excluding laboratory abnormalities) that occurred in at least 10% of patients. Table 4 presents the most common Grade 3 or 4 laboratory abnormalities, occurring in at least 10% of patients. Table 3: Adverse Reactions Occurring in ≥ 10% of Patients in FELIX Study (N=100) Adverse Reaction Any Grade (%) Grade 3 or Higher (%) Blood and lymphatic system disorders Febrile neutropenia 26 26 Coagulopathy Is a composite that includes multiple related terms. 10 6 Cardiac disorders Tachycardia 12 0 Gastrointestinal disorders Nausea 29 2 Diarrhea 26 0 Vomiting 18 0 Abdominal pain 16 1 Constipation 11 0 General disorders and administration site conditions Fever 29 1 Pain 23 0 Fatigue 22 3 Edema 12 0 Chills 11 0 Immune system disorders Cytokine release syndrome 75 3 Hypogammaglobulinemia 10 2 Infections and infestations Infections - pathogen unspecified 44 31 Viral infections excluding COVID-19 16 1 COVID-19 18 6 Bacterial infections 26 11 Fungal infections 15 5 Investigations Weight decreased 11 2 Metabolism and nutrition disorders Decreased appetite 13 3 Musculoskeletal and connective tissue disorders Musculoskeletal pain 36 4 Nervous system disorders Immune effector cell-associated neurotoxicity syndrome 24 7 Headache 22 0 Encephalopathy Encephalopathy includes aphasia, cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, dysarthria, dysgraphia, encephalopathy, lethargy, memory impairment, mental status changes, posterior reversible encephalopathy syndrome, somnolence. 21 4 Dizziness 14 0 Respiratory, thoracic and mediastinal disorders Cough 14 0 Skin and subcutaneous tissue disorders Rash 17 1 Vascular disorders Hypotension 23 4 Hemorrhage 20 4 Other clinically important adverse reactions that occurred in less than 10% of patients treated with AUCATZYL include the following: Cardiac disorders : arrhythmia (5%), palpitations (2%), cardiac failure (1%). Endocrine disorders : adrenal insufficiency (2%). Eye disorders: visual impairment (2%). Gastrointestinal disorders : stomatitis (5%), ascites (4%). Immune system disorders: graft versus host disease (4%), HLH/MAS (2%). Injury, poisoning and procedural complications : infusion related reaction (2%). Nervous system and psychiatric disorders : tremor (8%), motor dysfunction (6%), delirium (5%), seizure (2%). Renal disorders : renal impairment (7%). Respiratory disorders: respiratory failure (8%), pleural effusion (4%). Skin and subcutaneous tissue disorders: skin ulcer (2%). Vascular disorders: thrombosis (5%). Table 4: Grade 3 or 4 Laboratory abnormalities graded using NCI Common Terminology Criteria for Adverse Events version 5.0. Laboratory Abnormalities that Worsened from Baseline Baseline laboratory values were assessed prior to lymphodepleting chemotherapy. in ≥ 10% of Patients in FELIX Study (N=100) Laboratory Abnormality Grades 3 or 4 (%) Lymphocytopenia 90 Leukopenia 87 Neutropenia 72 Thrombocytopenia 48 Anemia 43 Hyperferritinemia 13 Aspartate aminotransferase increased 10 6.2 Postmarketing Experience Because adverse events to marketed products are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure. The following adverse event has been identified during postmarketing use of BCMA- or CD19-directed genetically modified autologous T cell immunotherapies: Neoplasms: T cell malignancies.
| Adverse Reaction | Any Grade (%) | Grade 3 or Higher (%) |
|---|---|---|
| Febrile neutropenia | 26 | 26 |
| Coagulopathy | 10 | 6 |
| Tachycardia | 12 | 0 |
| Nausea | 29 | 2 |
| Diarrhea | 26 | 0 |
| Vomiting | 18 | 0 |
| Abdominal pain | 16 | 1 |
| Constipation | 11 | 0 |
| Fever | 29 | 1 |
| Pain | 23 | 0 |
| Fatigue | 22 | 3 |
| Edema | 12 | 0 |
| Chills | 11 | 0 |
| Cytokine release syndrome | 75 | 3 |
| Hypogammaglobulinemia | 10 | 2 |
| Infections - pathogen unspecified | 44 | 31 |
| Viral infections excluding COVID-19 | 16 | 1 |
| COVID-19 | 18 | 6 |
| Bacterial infections | 26 | 11 |
| Fungal infections | 15 | 5 |
| Weight decreased | 11 | 2 |
| Decreased appetite | 13 | 3 |
| Musculoskeletal pain | 36 | 4 |
| Immune effector cell-associated neurotoxicity syndrome | 24 | 7 |
| Headache | 22 | 0 |
| Encephalopathy | 21 | 4 |
| Dizziness | 14 | 0 |
| Cough | 14 | 0 |
| Rash | 17 | 1 |
| Hypotension | 23 | 4 |
| Hemorrhage | 20 | 4 |
| Laboratory Abnormality | Grades 3 or 4 (%) |
|---|---|
| Lymphocytopenia | 90 |
| Leukopenia | 87 |
| Neutropenia | 72 |
| Thrombocytopenia | 48 |
| Anemia | 43 |
| Hyperferritinemia | 13 |
| Aspartate aminotransferase increased | 10 |
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action AUCATZYL is a CD19-directed genetically modified autologous T cell immunotherapy consisting of the patient's own T cells expressing an anti-CD19 CAR. Engagement of anti-CD19 CAR-positive T cells with CD19 expressed on target cells, such as cancer cells and normal B cells, leads to activation of the anti-CD19 CAR-positive T cells and downstream signaling through the CD3-zeta domain. Proliferation and persistence by the anti-CD19 CAR-positive T cells following activation are enhanced by the presence of the 4-1BB co-stimulatory domain. This binding to CD19 results in anti-tumor activity and killing of CD19-expressing target cells. 12.2 Pharmacodynamics Serum levels of cytokines such as IL-2, IL-5, IL-6, IL-7, IL-8, IL-10, IL-15, TNF-α, IFN-γ, and granulocyte-macrophage colony-stimulating factors were evaluated pre- and post-AUCATZYL infusion, over 3 months. Peak elevation of plasma cytokines was observed within the first month after infusion and levels returned to baseline by Month 3. Due to the on-target effect of AUCATZYL, a period of B cell aplasia is expected. B cell aplasia was observed in 93.1% of patients at 3 months and 80.0% at 6 months. 12.3 Pharmacokinetics The pharmacokinetics (PK) of AUCATZYL were assessed in 90 patients with relapsed or refractory CD19+ B-ALL receiving a median dose of 410 × 10 6 CD19 CAR-positive viable T cells (range: 10 to 480 × 10 6 CD19 CAR-positive viable T cells). Following Day 1 infusion, levels of the AUCATZYL transgene in peripheral blood exhibited an initial rapid expansion. The median time of maximal expansion to peak (T max ) occurred at Day 14 (range: Day 2-55), demonstrated by a geometric mean peak CAR T concentration (C max ) of 115,193 copies/µg genomic DNA (gDNA; range, 129-600,000) and a geometric mean area under the curve between Days 0 and 28 (AUC 0-28d ) of 1,147,631 day*copies/μg DNA (range 179,000-7,230,000 day*copies/μg DNA). A higher expansion was observed in patients with bone marrow blasts >20% compared to patients with bone marrow blast ≤ 20%. Table 5: Summary of Pharmacokinetics Parameters for Transgene Levels by ddPCR in Peripheral Blood by Dose Regimen Received Parameter Statistics Bone Marrow Blast Bone Marrow Blast > 20% = dosage regimen of 10 × 10 6 then 400 × 10 6 CD19 CAR-positive viable T cells . > 20% (N=59) Bone Marrow Blast Bone Marrow Blast ≤ 20% = dosage regimen 100 × 10 6 then 310 × 10 6 CD19 CAR-positive viable T cells. ≤ 20% (N=31) Total (N=90) AUC 0-28d =area under the concentration-time curve (exposure) from Day 0 to Day 28; C max = maximum serum concentration; ddPCR = droplet digital polymerase chain reaction; DNA = deoxyribonucleic acid; Geo-CV% = geometric mean coefficient of variation; T max = time to maximum concentration. C max (copies/μg DNA) n 59 31 90 Geometric Mean (Geo-CV%) 146,314 (294.4) 73,074 (186.9) 115,193 (267.0) Min – Max 129 – 600,000 9290 – 589,000 129 – 600,000 T max (days) n 59 31 90 Median 20 11 14 Min – Max 6 – 55 2 – 28 2 – 55 AUC 0-28d (day*copies/μg DNA) n 52 29 81 Geometric Mean (Geo-CV%) 1,521,310 (191.3) 692,307 (226.8) 1,147,631 (219.5) Min – Max 17,900 – 6,730,000 70,400 – 7,230,000 17,900 – 7,230,000 No substantial differences in AUCATZYL expansion were observed between responding (CR/CRi) and non-responding (non- CR/CRi) patients. Furthermore, 75.9% (22/29) of patients who had ongoing remission had ongoing CAR T persistency at the last laboratory assessment, with a maximum observed persistency of 36.5 months. Patients who received a first split dose of 10 × 10 6 cells (> 20% blast) demonstrated a higher expansion of CAR T cells (C max and AUC 0-28d ) compared to patients who received a first split dose of 100 × 10 6 cells (≤ 20% blast). Persistency was not impacted by tumor burden. Patients who experience CRS had 1.8-fold higher mean bone marrow blast percentage and higher CAR T cell expansion (5.0-fold higher C max and 6.8-fold higher AUC 0-28d [(geometric mean)]) compared to patients without CRS. Patients who experience ICANS had 1.8-fold higher mean bone marrow blast percentage and higher CAR T cell expansion (3.3-fold higher C max and 2.9-fold higher AUC 0-28d (geometric mean)) compared to patients without ICANS. Specific populations Sex did not have a significant impact on the PK of AUCATZYL (C max , AUC 0-28d or persistency). Hepatic and renal impairment studies of AUCATZYL were not conducted. 12.4 Immunogenicity The humoral immunogenicity of AUCATZYL was measured using an assay for the detection of anti-drug antibodies against AUCATZYL. In the FELIX study, 8.7% (11/127) of patients tested positive for anti-CD19 CAR antibodies pre-infusion. Treatment induced anti-CD19 CAR antibodies were detected in 1.6% (2/127) of patients. The cellular immunogenicity of AUCATZYL was measured using an assay for the detection of T cell responses, measured by the production of interferon gamma (IFNγ) to the full length anti-CD19 CAR. Four percent (3/75) of patients tested positive in the cellular immunogenicity readout (IFNγ) post infusion. There was no identified clinically significant effect of humoral and cellular immunogenicity on pharmacokinetics, pharmacodynamics, safety, or effectiveness of AUCATZYL.
| Parameter | Statistics | Bone Marrow Blast | Bone Marrow Blast | Total (N=90) |
|---|---|---|---|---|
| AUC0-28d=area under the concentration-time curve (exposure) from Day 0 to Day 28; Cmax = maximum serum concentration; ddPCR = droplet digital polymerase chain reaction; DNA = deoxyribonucleic acid; Geo-CV% = geometric mean coefficient of variation; Tmax = time to maximum concentration. | ||||
| Cmax (copies/μg DNA) | n | 59 | 31 | 90 |
| Geometric Mean (Geo-CV%) | 146,314 (294.4) | 73,074 (186.9) | 115,193 (267.0) | |
| Min – Max | 129 – 600,000 | 9290 – 589,000 | 129 – 600,000 | |
| Tmax (days) | n | 59 | 31 | 90 |
| Median | 20 | 11 | 14 | |
| Min – Max | 6 – 55 | 2 – 28 | 2 – 55 | |
| AUC0-28d (day*copies/μg DNA) | n | 52 | 29 | 81 |
| Geometric Mean (Geo-CV%) | 1,521,310 (191.3) | 692,307 (226.8) | 1,147,631 (219.5) | |
| Min – Max | 17,900 – 6,730,000 | 70,400 – 7,230,000 | 17,900 – 7,230,000 | |
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 Mechanism of Action AUCATZYL is a CD19-directed genetically modified autologous T cell immunotherapy consisting of the patient's own T cells expressing an anti-CD19 CAR. Engagement of anti-CD19 CAR-positive T cells with CD19 expressed on target cells, such as cancer cells and normal B cells, leads to activation of the anti-CD19 CAR-positive T cells and downstream signaling through the CD3-zeta domain. Proliferation and persistence by the anti-CD19 CAR-positive T cells following activation are enhanced by the presence of the 4-1BB co-stimulatory domain. This binding to CD19 results in anti-tumor activity and killing of CD19-expressing target cells.
Pharmacodynamics
Information about any biochemical or physiologic pharmacologic effects of the drug or active metabolites related to the drugÕs clinical effect in preventing, diagnosing, mitigating, curing, or treating disease, or those related to adverse effects or toxicity.12.2 Pharmacodynamics Serum levels of cytokines such as IL-2, IL-5, IL-6, IL-7, IL-8, IL-10, IL-15, TNF-α, IFN-γ, and granulocyte-macrophage colony-stimulating factors were evaluated pre- and post-AUCATZYL infusion, over 3 months. Peak elevation of plasma cytokines was observed within the first month after infusion and levels returned to baseline by Month 3. Due to the on-target effect of AUCATZYL, a period of B cell aplasia is expected. B cell aplasia was observed in 93.1% of patients at 3 months and 80.0% at 6 months.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics The pharmacokinetics (PK) of AUCATZYL were assessed in 90 patients with relapsed or refractory CD19+ B-ALL receiving a median dose of 410 × 10 6 CD19 CAR-positive viable T cells (range: 10 to 480 × 10 6 CD19 CAR-positive viable T cells). Following Day 1 infusion, levels of the AUCATZYL transgene in peripheral blood exhibited an initial rapid expansion. The median time of maximal expansion to peak (T max ) occurred at Day 14 (range: Day 2-55), demonstrated by a geometric mean peak CAR T concentration (C max ) of 115,193 copies/µg genomic DNA (gDNA; range, 129-600,000) and a geometric mean area under the curve between Days 0 and 28 (AUC 0-28d ) of 1,147,631 day*copies/μg DNA (range 179,000-7,230,000 day*copies/μg DNA). A higher expansion was observed in patients with bone marrow blasts >20% compared to patients with bone marrow blast ≤ 20%. Table 5: Summary of Pharmacokinetics Parameters for Transgene Levels by ddPCR in Peripheral Blood by Dose Regimen Received Parameter Statistics Bone Marrow Blast Bone Marrow Blast > 20% = dosage regimen of 10 × 10 6 then 400 × 10 6 CD19 CAR-positive viable T cells . > 20% (N=59) Bone Marrow Blast Bone Marrow Blast ≤ 20% = dosage regimen 100 × 10 6 then 310 × 10 6 CD19 CAR-positive viable T cells. ≤ 20% (N=31) Total (N=90) AUC 0-28d =area under the concentration-time curve (exposure) from Day 0 to Day 28; C max = maximum serum concentration; ddPCR = droplet digital polymerase chain reaction; DNA = deoxyribonucleic acid; Geo-CV% = geometric mean coefficient of variation; T max = time to maximum concentration. C max (copies/μg DNA) n 59 31 90 Geometric Mean (Geo-CV%) 146,314 (294.4) 73,074 (186.9) 115,193 (267.0) Min – Max 129 – 600,000 9290 – 589,000 129 – 600,000 T max (days) n 59 31 90 Median 20 11 14 Min – Max 6 – 55 2 – 28 2 – 55 AUC 0-28d (day*copies/μg DNA) n 52 29 81 Geometric Mean (Geo-CV%) 1,521,310 (191.3) 692,307 (226.8) 1,147,631 (219.5) Min – Max 17,900 – 6,730,000 70,400 – 7,230,000 17,900 – 7,230,000 No substantial differences in AUCATZYL expansion were observed between responding (CR/CRi) and non-responding (non- CR/CRi) patients. Furthermore, 75.9% (22/29) of patients who had ongoing remission had ongoing CAR T persistency at the last laboratory assessment, with a maximum observed persistency of 36.5 months. Patients who received a first split dose of 10 × 10 6 cells (> 20% blast) demonstrated a higher expansion of CAR T cells (C max and AUC 0-28d ) compared to patients who received a first split dose of 100 × 10 6 cells (≤ 20% blast). Persistency was not impacted by tumor burden. Patients who experience CRS had 1.8-fold higher mean bone marrow blast percentage and higher CAR T cell expansion (5.0-fold higher C max and 6.8-fold higher AUC 0-28d [(geometric mean)]) compared to patients without CRS. Patients who experience ICANS had 1.8-fold higher mean bone marrow blast percentage and higher CAR T cell expansion (3.3-fold higher C max and 2.9-fold higher AUC 0-28d (geometric mean)) compared to patients without ICANS. Specific populations Sex did not have a significant impact on the PK of AUCATZYL (C max , AUC 0-28d or persistency). Hepatic and renal impairment studies of AUCATZYL were not conducted.
| Parameter | Statistics | Bone Marrow Blast | Bone Marrow Blast | Total (N=90) |
|---|---|---|---|---|
| AUC0-28d=area under the concentration-time curve (exposure) from Day 0 to Day 28; Cmax = maximum serum concentration; ddPCR = droplet digital polymerase chain reaction; DNA = deoxyribonucleic acid; Geo-CV% = geometric mean coefficient of variation; Tmax = time to maximum concentration. | ||||
| Cmax (copies/μg DNA) | n | 59 | 31 | 90 |
| Geometric Mean (Geo-CV%) | 146,314 (294.4) | 73,074 (186.9) | 115,193 (267.0) | |
| Min – Max | 129 – 600,000 | 9290 – 589,000 | 129 – 600,000 | |
| Tmax (days) | n | 59 | 31 | 90 |
| Median | 20 | 11 | 14 | |
| Min – Max | 6 – 55 | 2 – 28 | 2 – 55 | |
| AUC0-28d (day*copies/μg DNA) | n | 52 | 29 | 81 |
| Geometric Mean (Geo-CV%) | 1,521,310 (191.3) | 692,307 (226.8) | 1,147,631 (219.5) | |
| Min – Max | 17,900 – 6,730,000 | 70,400 – 7,230,000 | 17,900 – 7,230,000 | |
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4 CONTRAINDICATIONS None. None ( 4 ).
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11 DESCRIPTION AUCATZYL (obecabtagene autoleucel) is a CD19-directed genetically modified autologous T cell immunotherapy comprised of the patient's T cells that are transduced with a lentiviral vector to express an anti-CD19 chimeric antigen receptor (CAR). The CAR is composed of a murine anti-CD19 single chain variable fragment (scFv) linked to 4-1BB and CD3-zeta co-stimulatory domains. AUCATZYL is prepared from the patient's own peripheral blood mononuclear cells, which are collected via a standard leukapheresis procedure. The mononuclear cells are enriched for T cells, activated and transduced with a replication-incompetent lentiviral vector containing the CD19 CAR transgene. The transduced T cells are expanded in cell culture, washed, formulated into a suspension, and then cryopreserved. AUCATZYL is frozen in patient-specific infusion bag(s) and thawed prior to infusion [see Dosage and Administration (2.3) , How Supplied/Storage and Handling (16) ]. The product must pass a sterility test before it is released to the treatment center. The thawed product is a colorless to pale yellow, very opalescent suspension that is essentially free from visible foreign particles. In addition to T cells, AUCATZYL also contains non-transduced autologous T cells and non-T cells. The formulation contains phosphate-buffered saline (PBS) human serum albumin (HSA), ethylenediaminetetraacetic acid (EDTA) and 7.5% DMSO.
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2 DOSAGE AND ADMINISTRATION For autologous use only. For intravenous use only. Strictly follow Administration instructions to minimize dosing errors [see Overdosage (10) . For autologous use only. For intravenous use only. Do NOT use a leukodepleting filter ( 2.4 ). Prior to infusion Administer a lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide. ( 2.3 ). Ensure availability of bone marrow assessment results from a sample obtained within 7 days prior to start of lymphodepleting chemotherapy ( 2.3 ). Premedicate with acetaminophen ( 2.3 ). Confirm availability of tocilizumab prior to infusion ( 2.3 ). AUCATZYL Dose and Administration Verify patient's identity prior to infusion ( 2.3 ). Dosing is based on the Dose Schedule Planner ( 2.3 ). The total recommended dose of AUCATZYL is 410 × 10 6 CD19 chimeric antigen receptor (CAR)-positive viable T cells ( 2.1 ). The treatment regimen consists of a split dose infusion to be administered on Day 1 and Day 10 (± 2 days) ( 2.1 ). Dose to be administered is determined by the patient bone marrow blast assessment. See Full Prescribing Information for important preparation and administration information ( 2.3 , 2.4 ). 2.1 Dose The total recommended dose of AUCATZYL is 410 × 10 6 CD19 chimeric antigen receptor (CAR)-positive viable T cells supplied in three to five infusion bags. Bags are supplied in three color-coded bag configurations (10 × 10 6 , 100 × 10 6 , 300 × 10 6 ) for split dose administration. Table 1: AUCATZYL Infusion Bag Configurations CAR+ T Cell Dose (Bag Configuration) Color Code Volume Fully Infused 10 × 10 6 Blue 10mL No (See Section 2.3 ) 100 × 10 6 Orange Variable Yes 300 × 10 6 Red Variable Yes The treatment regimen consists of a split dose infusion to be administered on Day 1 and Day 10 (± 2 days), see Figure 1 and Figure 3 . The dosage regimen will be determined by the tumor burden assessed by bone marrow blast percentage from a sample obtained within 7 days prior to the start of lymphodepletion [see Dosing and Administration (2.3 , 2.4) , Figure 1 and Figure 3 ]. See the Release for Infusion certificate and Dose Schedule Planner for the actual cell counts and volumes to be infused and to select the appropriate dosage regimen [see Dosage and Administration (2.4 , 2.4) and Dosage Forms and Strengths (3) ]. 2.2 Dosage Modification for Adverse Reactions Table 2: Dosage Modifications Intended to Reduce the Risk of Adverse Reactions Adverse Event Severity Based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, and Grade 4 is life-threatening. Actions Second Split Dose Day 10 (±2 days) Cytokine Release Syndrome following the first split dose [see Warnings and Precautions (5.1) ]. Grade 2 Consider postponing AUCATZYL infusion up to Day 21 to allow for the CRS to resolve to Grade ≤ 1. Grade ≥ 3 Discontinue treatment. Immune Effector Cell-associated Neurotoxicity Syndrome following the first split dose [see Warnings and Precautions (5.2) ]. Grade 1 Consider postponing AUCATZYL infusion up to Day 21 to allow for the ICANS to completely resolve. Grade ≥ 2 Discontinue treatment. Pulmonary or cardiac toxicities following the first split dose. Grade ≥ 3 Discontinue treatment. Severe intercurrent infection at the time of AUCATZYL infusion [see Warnings and Precautions (5.4) ]. Grade ≥ 3 Consider postponing AUCATZYL infusion up to Day 21 until the severe intercurrent infection is considered controlled. Requirement for supplementary oxygen. Grade ≥ 3 Consider postponing AUCATZYL treatment up to Day 21 to allow for the adverse reaction to resolve. Other clinically relevant adverse reactions following the first split dose [see Warnings and Precautions (5) ]. Grade ≥ 3 Consider postponing AUCATZYL infusion up to Day 21 to allow for the adverse reaction to resolve. 2.3 Administration AUCATZYL is for autologous use only. The patient's identity must match the patient identifiers on the AUCATZYL infusion bag. Do not infuse AUCATZYL if the information on the patient-specific label does not match the intended patient. Preparing the Patient for AUCATZYL Infusion Bone marrow assessment A bone marrow assessment must be available from a sample obtained within 7 days prior to the commencement of the lymphodepleting chemotherapy treatment, see Figure 1 . Figure 1: AUCATZYL Treatment Schedule The bone marrow assessment will be used to determine the AUCATZYL dosage regimen based on a Bone Marrow Blast of > 20% or ≤ 20%, see Figure 3 . If the bone marrow assessment results are inconclusive: - Repeat biopsy or aspirate, NOTE a repeat biopsy or aspirate is only possible if lymphodepleting chemotherapy treatment has not started. - If results remain inconclusive, proceed with the Bone Marrow Blast of > 20% (i.e., administration of the 10 × 10 6 dose on Day 1) per the AUCATZYL Dose Schedule Planner. Figure 1 Pretreatment Confirm availability of AUCATZYL prior to starting the lymphodepleting chemotherapy treatment. Administer the lymphodepleting chemotherapy regimen before infusion of AUCATZYL: fludarabine (FLU) 30 mg/m 2 /day intravenously (IV) for four days and cyclophosphamide (CY) 500 mg/m 2 /day IV for two days starting with the first dose of fludarabine. (total dose: FLU 120 mg/m 2 ; CY 1000 mg/m 2 ), see Figure 1 . Infuse AUCATZYL 3 days (± 1 days) after completion of lymphodepleting chemotherapy treatment (Day 1), allowing a minimum 48-hour washout. Delay AUCATZYL treatment if the patient is experiencing severe intercurrent infection. If the patient requires supplementary oxygen AUCATZYL should only be infused if considered appropriate based on the treating physician's benefit/risk assessment. A delay to the second split dose may be required to manage toxicities [see Dosage Modification for Adverse Reactions (2.2) and Warnings and Precautions (5) ]. Premedication To minimize the risk of an infusion reaction, premedicate with acetaminophen approximately 30 minutes prior to AUCATZYL infusion. Avoid prophylactic use of systemic corticosteroids as they may interfere with the activity of AUCATZYL. Receipt and storage of AUCATZYL AUCATZYL is supplied directly to the cellular therapy laboratory associated with the infusion center in the vapor phase of a liquid nitrogen shipper [see How Supplied/Storage and Handling (16) ]. Confirm the patient's identity on the infusion bags with the patient identifiers on the shipper, see Figure 2 . Figure 2: Patient Specific Identifiers Keep the infusion bag(s) in the metal cassette(s) and transfer AUCATZYL to the onsite controlled-access vapor phase of liquid nitrogen for storage below minus 150°C until ready for thaw and administration. Time out of the vapor phase liquid nitrogen environment should be kept to an absolute minimum to avoid premature product thaw (recommend not to exceed 90 seconds). Figure 2 Planning prior to AUCATZYL preparation The patient batch specific Release for Infusion certificate and Dose Schedule Planner will be provided in the shipper and via Autolus's Scheduling Portal. Confirm the patient identifiers on the Release for Infusion certificate and infusion bags match, see Figure 2 . Ensure the patient's bone marrow assessment results are available. – NOTE: The patient's bone marrow assessment results will be used to select the appropriate dosing regimen based on a Bone Marrow Blast of > 20% or ≤ 20%, see Figure 3 . The AUCATZYL Dose Schedule Planner is provided with the Release for Infusion certificate and assists the determination of the appropriate dose regimen to be administered on Day 1 (3 days (±1 days) after the completion of lymphodepleting chemotherapy) and Day 10 (± 2 days). Record the following information on the Dose Schedule Planner: The blast percentage from the patient's bone marrow assessment. The AUCATZYL bag serial number(s); number of bag type required for each dose; and the specified volume to administer via syringe (for the 10 × 10 6 dose, Blue Bag) transcribed from the Release for Infusion certificate. The completion of the AUCATZYL Dose Schedule Planner will guide the treating physician on the number of bags required and preparation of AUCATZYL for the Day 1 and Day 10 (± 2 days) dose, see Figure 3 . Dose Preparation Do NOT irradiate. Do NOT use a leukodepleting filter. Confirm the patient's identity with the patient identifiers on the Release for Infusion certificate. Contact Autolus Inc at 1-855-288-5227 if there are any discrepancies between the labels and the patient identifiers. Confirm tocilizumab and emergency equipment are available prior to infusion and during the recovery period. Coordinate the timing of AUCATZYL thaw and infusion. Confirm the infusion time in advance and adjust the start time of AUCATZYL thaw such that it will be available for infusion when the patient is ready and will be infused within 60 minutes of thaw. Complete the AUCATZYL Dose Schedule Planner, as described above to identify the dose required for Day 1 and Day 10 (± 2 days) administration, see Figure 3 . Follow the completed AUCATZYL Dose Schedule Planner and refer to the patient batch specific Release for Infusion certificate to verify the bag(s) required for Day 1 or Day 10 (± 2 days) dosing, see Figure 3 . Transfer and Thawing Using the completed Dose Schedule Planner for guidance, transfer ONLY the cassette(s)/ infusion bag(s) required for the given dosing day from the onsite vapor phase liquid nitrogen storage to an appropriate transfer vessel (i.e., a vapor phase liquid nitrogen shipper, maintaining a temperature below minus 150°C) for transport to the bag thaw location. Transfer the required cassette(s) one by one, confirming the AUCATZYL bag serial numbers and patient identifiers on each infusion bag label, see Figure 2 . Time out of the vapor phase liquid nitrogen environment should be kept to an absolute minimum to avoid premature product thaw (recommend not to exceed 90 seconds). If more than one infusion bag is required on a given dosing day, thaw each infusion bag one at a time; Do NOT remove subsequent bags from the vapor phase liquid nitrogen storage (below minus 150°C) until the infusion of the previous bag is complete. AUCATZYL must be continuously monitored during thawing process. Leave the AUCATZYL infusion bag in its overwrap, thaw at 37°C using a water bath or dry thaw method until there are no visible frozen clumps left in the infusion bag. Each bag should be gently massaged until the cells have just thawed. Thawing of each infusion bag takes between 2 and 8 minutes. Remove from water bath or thaw device immediately after thawing is complete. Carefully remove the infusion bag from the overwrap taking care to avoid damage to the bag and ports. Gently mix the contents of the bag to disperse clumps of cellular material and administer immediately to the patient. Do not re-freeze or refrigerate thawed product. Figure 3: AUCATZYL Dosage and Schedule Bone Marrow Blast > 20% Day 1 Day 10 (± 2 days) 10 × 10 6 Dose administered via syringe Refer to Release for Infusion Certificate for the exact volume to be administered via syringe. Withdraw ONLY the volume 100 × 10 6 Dose administered via bag infusion The 100 × 10 6 (Orange Bag) and 300 × 10 6 (Red Bag) doses will be suspended in one or more infusion bags. and 300 × 10 6 Dose administered via bag infusion Bone Marrow Blast ≤ 20% Day 1 Day 10 (± 2 days) 100 × 10 6 Dose administered via bag infusion 10 × 10 6 Dose administered via syringe and 300 × 10 6 Dose administered via bag infusion Image Image 2.4 Infusion Instructions AUCATZYL is for autologous and intravenous use only. The patient's identity must match the patient identifiers on the Release for Infusion certificate and infusion bag. Contact Autolus Inc at 1-855-288-5227 if there are any discrepancies between the labels and the patient identifiers. Dose administration for 10 × 10 6 CD19 CAR-positive viable T cell Dose (Blue Bag) Withdrawal of the 10 × 10 6 dose into the syringe should be carried as follows: Prepare and administer AUCATZYL using aseptic technique. Gently mix the contents of the bag to disperse clumps of cellular material. The volume to be administered for the 10 × 10 6 dose (Blue Bag) is specified on the Release for Infusion certificate. Use the smallest Luer-lock tip syringe necessary (1, 3, 5, or 10 mL) with a Luer-lock bag spike to draw up the volume as specified on the Release for Infusion certificate. – Do NOT use a leukodepleting filter. – Do NOT use the syringe to mix the cells, see Figure 4 . Figure 4: Syringe Infusion Guidance for the 10 × 10 6 Dose (Blue Bag) Withdraw the volume from the 10 × 10 6 Dose (Blue Bag) specified on the Release for Infusion certificate using a syringe fitted with a bag spike. Do not use the syringe to mix the cells Confirm withdrawal of the exact volume specified on the Release for Infusion certificate for the 10 × 10 6 Dose (Blue Bag). Prime the tubing with normal saline prior to infusion. Once AUCATZYL has been drawn into the syringe, verify the volume and administer as an intravenous infusion as soon as possible as a slow push (approximately 0.5mL/minute) through a central venous line (or large peripheral venous access line appropriate for blood products). Complete infusion at room temperature within 60 minutes post thaw and flush the tubing line with 60 mL of normal saline. Dispose of any unused portion of AUCATZYL (according to local biosafety guidelines). Image Image Image Dose administration for 100 × 10 6 (Orange Bag) and/or 300 × 10 6 (Red Bag) CD19 CAR-positive viable T cells Refer to the Release for Infusion certificate and Dose Schedule Planner for the following details: - The volume and total CD19 CAR-positive viable T cell number contained in each infusion bag. - The dose to be administered on the given dosing day and the number of bags required to deliver the specified CD19 CAR-positive viable T cell dose. - If more than one bag is needed, thaw subsequent bags after the previous bag is fully administered. Prime the tubing with normal saline prior to infusion. Administer AUCATZYL via a gravity or peristaltic pump assisted IV infusion through a central venous line (or large peripheral venous access line appropriate for blood products). – Do NOT use a leukodepleting filter. – Aseptic techniques must be applied when performing a venepuncture, spiking the ports, and through the cell administration process. – Gently mix the contents of the bag during AUCATZYL infusion to disperse cell clumps. Infuse the entire content of the AUCATZYL infusion bag at room temperature within 60 minutes post thaw (infusion rate within 0.1 to 27 mL/minute). – After the entire content of the infusion bag is infused, rinse the bag with 30 mL of normal saline, then flush the tubing line with 60 mL of normal saline. – Repeat steps 1- 3 for any additional infusion bags required on the given dosing day. Do NOT initiate thaw of the next bag until infusion of the previous bag is complete. AUCATZYL contains human blood cells that are genetically modified with replication-incompetent lentiviral vector. Follow universal precautions and local biosafety guidelines for handling and disposal of AUCATZYL to avoid potential transmission of infectious diseases. Monitoring Monitor patients for signs and symptoms of CRS, neurologic toxicities/ICANS and other acute toxicities daily for at least 14 days at the healthcare facility following the first infusion. Continue to monitor patients for at least 4 weeks following each infusion. Instruct patients to remain within proximity of a healthcare facility for at least 4 weeks following the first infusion. Instruct patients to refrain from driving or hazardous activities for at least 8 weeks following infusion.
| CAR+ T Cell Dose (Bag Configuration) | Color Code | Volume | Fully Infused |
|---|---|---|---|
| 10 × 106 | Blue | 10mL | |
| 100 × 106 | Orange | Variable | Yes |
| 300 × 106 | Red | Variable | Yes |
| Adverse Event | Severity | Actions |
|---|---|---|
| Second Split Dose Day 10 (±2 days) | ||
| Cytokine Release Syndrome following the first split dose | Grade 2 | Consider postponing AUCATZYL infusion up to Day 21 to allow for the CRS to resolve to Grade ≤ 1. |
| Grade ≥ 3 | Discontinue treatment. | |
| Immune Effector Cell-associated Neurotoxicity Syndrome following the first split dose | Grade 1 | Consider postponing AUCATZYL infusion up to Day 21 to allow for the ICANS to completely resolve. |
| Grade ≥ 2 | Discontinue treatment. | |
| Pulmonary or cardiac toxicities following the first split dose. | Grade ≥ 3 | Discontinue treatment. |
| Severe intercurrent infection at the time of AUCATZYL infusion | Grade ≥ 3 | Consider postponing AUCATZYL infusion up to Day 21 until the severe intercurrent infection is considered controlled. |
| Requirement for supplementary oxygen. | Grade ≥ 3 | Consider postponing AUCATZYL treatment up to Day 21 to allow for the adverse reaction to resolve. |
| Other clinically relevant adverse reactions following the first split dose | Grade ≥ 3 | Consider postponing AUCATZYL infusion up to Day 21 to allow for the adverse reaction to resolve. |
| Withdraw the volume from the 10 × 106 Dose (Blue Bag) specified on the Release for Infusion certificate using a syringe fitted with a bag spike. | Do not use the syringe to mix the cells | Confirm withdrawal of the exact volume specified on the Release for Infusion certificate for the 10 × 106 Dose (Blue Bag). |
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3 DOSAGE FORMS AND STRENGTHS AUCATZYL is a cell suspension for infusion. AUCATZYL contains a total recommended dose of 410 × 10 6 CD19 CAR-positive viable T cells supplied in three to five infusion bags. The infusion volume is variable and is calculated based on the concentration of CD19 CAR-positive viable T cells [see How Supplied/Storage and Handling (16) ]. See the Release for Infusion certificate for actual cell counts. The Release for Infusion certificate and Dose Schedule Planner will be provided to the infusion site in the product shipper and via Autolus's Scheduling Portal. AUCATZYL is a cell suspension for infusion ( 3 ). AUCATZYL contains a total recommended dose of 410 × 10 6 CD19 CAR-positive viable T cells supplied in 3 to 5 infusion bags ( 3 ).
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATION AND USAGE AUCATZYL is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). AUCATZYL is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) ( 1 ).
Spl product data elements
Usually a list of ingredients in a drug product.AUCATZYL Obecabtagene autoleucel AUCATZYL Obecabtagene autoleucel Obecabtagene autoleucel Obecabtagene autoleucel AUCATZYL Obecabtagene autoleucel Obecabtagene autoleucel Obecabtagene autoleucel AUCATZYL Obecabtagene autoleucel Obecabtagene autoleucel Obecabtagene autoleucel
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No in vivo or in vitro carcinogenicity, mutagenicity or genotoxicity studies have been conducted with AUCATZYL. No studies have been conducted to evaluate the effects of AUCATZYL on fertility.
Nonclinical toxicology
Information about toxicology in non-human subjects.13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No in vivo or in vitro carcinogenicity, mutagenicity or genotoxicity studies have been conducted with AUCATZYL. No studies have been conducted to evaluate the effects of AUCATZYL on fertility.
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.PRINCIPAL DISPLAY PANEL - 10 mL Infusion Bag Label - 10 x 10 10x10 6 bag configuration EXTRACT SPECIFIED VOLUME VIA SYRINGE obecabtagene autoleucel AUCATZYL ® FOR AUTOLOGOUS & INTRAVENOUS USE ONLY. Dosage: See prescribing information and release for infusion certificate. Discard unused portion. Contains: Up to 100x10 6 CD19 CAR-positive viable T cells in 10mL suspension containing 7.5% DMSO USP. DO NOT USE A LEUKODEPLETING FILTER OR IRRADIATE. Storage: Ship and store in vapor phase of liquid nitrogen ≤ -150°C. Not evaluated for infectious substances. Rx Only US License 2339 A1001-01 Autolus Mfd by: Autolus Ltd, Stevenage, SG1 1FR, UK Mfd for: Autolus Inc., Gaithersburg, MD, 20877 Phone: 1-855-288-5227 PRINCIPAL DISPLAY PANEL - 10 mL Infusion Bag Label - 10 x 10
PRINCIPAL DISPLAY PANEL - 10 mL to 20 mL Infusion Bag Label - 100 x 10 100x10 6 bag configuration obecabtagene autoleucel AUCATZYL ® FOR AUTOLOGOUS & INTRAVENOUS USE ONLY. Dosage: See prescribing information and the release for infusion certificate. Contains: 100x10 6 CD19 CAR-positive viable T cells in 10mL to 20mL suspension containing 7.5% DMSO USP. Dose may be suspended in 1 or more infusion bag(s). DO NOT USE A LEUKODEPLETING FILTER OR IRRADIATE. Storage: Ship and store in vapor phase of liquid nitrogen ≤ -150°C. Not evaluated for infectious substances. Rx Only US License 2339 D1001-01 Autolus Mfd by: Autolus Ltd, Stevenage, SG1 1FR, UK Mfd for: Autolus Inc., Gaithersburg, MD, 20877 Phone: 1-855-288-5227 PRINCIPAL DISPLAY PANEL - 10 mL to 20 mL Infusion Bag Label - 100 x 10
PRINCIPAL DISPLAY PANEL - 30 mL to 70 mL Infusion Bag Label - 100 x 10 100x10 6 bag configuration obecabtagene autoleucel AUCATZYL ® FOR AUTOLOGOUS & INTRAVENOUS USE ONLY. Dosage: See prescribing information and the release for infusion certificate. Contains: 100x10 6 CD19 CAR-positive viable T cells in 30mL to 70mL suspension containing 7.5% DMSO USP. DO NOT USE A LEUKODEPLETING FILTER OR IRRADIATE. Storage: Ship and store in vapor phase of liquid nitrogen ≤ -150°C. Not evaluated for infectious substances. Rx Only US License 2339 B1001-01 Autolus Mfd by: Autolus Ltd, Stevenage, SG1 1FR, UK Mfd for: Autolus Inc., Gaithersburg, MD, 20877 Phone: 1-855-288-5227 PRINCIPAL DISPLAY PANEL 30 mL to 70 mL Infusion Bag Label - 100 x 10
PRINCIPAL DISPLAY PANEL - 30 mL to 70 mL Infusion Bag Label - 300 x 10 300x10 6 bag configuration obecabtagene autoleucel AUCATZYL ® FOR AUTOLOGOUS & INTRAVENOUS USE ONLY. Dosage: See prescribing information and the release for infusion certificate. Contains: 300x10 6 CD19 CAR-positive viable T cells in 30mL to 70mL suspension containing 7.5% DMSO USP. Dose may be suspended in 1 or more infusion bag(s). DO NOT USE A LEUKODEPLETING FILTER OR IRRADIATE. Storage: Ship and store in vapor phase of liquid nitrogen ≤ -150°C. Not evaluated for infectious substances. Rx Only US License 2339 C1001-01 Autolus Mfd by: Autolus Ltd, Stevenage, SG1 1FR, UK Mfd for: Autolus Inc., Gaithersburg, MD, 20877 Phone: 1-855-288-5227 PRINCIPAL DISPLAY PANEL - 30 mL to 70 mL Infusion Bag Label - 300 x 10
PRINCIPAL DISPLAY PANEL - Patient Information Label obecabtagene autoleucel AUCATZYL ® VERIFY PATIENT ID Aph ID: Lot/COI ID: Patient Hospital ID: First Name M.I.: Last Name: DOB: DD-MMM-YYYY Expiry: DD-MMM-YYYY S/N: A P1001-01 PRINCIPAL DISPLAY PANEL - Patient Information Label
PRINCIPAL DISPLAY PANEL - Kit Label obecabtagene autoleucel AUCATZYL ® FOR AUTOLOGOUS & INTRAVENOUS USE ONLY. Dose: 410 x 10 6 CD19 CAR-positive viable T cells Dosage: See prescribing information and the release for infusion certificate. Contains: AUCATZYL is a frozen cell suspension containing 7.5% DMSO. Supplied in three to five infusion bag(s) in one or two packs. Ship and store in vapor phase of liquid nitrogen ≤ -150°C. Upon receipt, immediately transfer to a vapor phase liquid nitrogen environment (≤ -150°C). Do not refreeze. DO NOT USE A LEUKODEPLETING FILTER OR IRRADIATE. Rx Only KIT NDC: 83047-410-04 Lot/COI ID : Aph ID : Expiry : DD-MMM-YYYY 1/X Pack Autolus M3001-01 Manufactured by Autolus Ltd, Stevenage, SG1 1FR, UK Manufactured for Autolus Inc., Gaithersburg, MD, 20877 Phone: 1-855-288-5227 US License 2339 PRINCIPAL DISPLAY PANEL - Kit Label
AUCATZYL: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Discuss the following with the patient: Inform patients that there is a risk of manufacturing failure (4.5% [5/112 in clinical studies]). Therefore, a second manufacturing of AUCATZYL may be attempted, after a second leukapheresis collection. Inform patients that additional therapy (other than lymphodepletion) may be necessary before AUCATZYL manufacturing is completed. This may increase the risk of adverse events during the pre-infusion period, which could delay or prevent the administration of AUCATZYL. Advise patients to seek immediate attention if any of the following occur: Cytokine Release Syndrome : Inform patients that symptoms may include- fever, hypotension and hypoxia [see Warnings and Precautions (5.1) and Adverse Reactions (6) ]. Neurologic Toxicity/ICANS: Inform patients that symptoms may include ICANS, headache, dizziness, anxiety, insomnia, delirium, tremor, and encephalopathy [see Warnings and Precautions (5.2) and Adverse Reactions (6) ]. Prolonged Cytopenias: Inform patients that symptoms may include neutropenia, anemia, thrombocytopenia, or bleeding [see Warnings and Precautions (5.3) and Adverse Reactions (6) ]. Severe Infections: Inform patients that they may exhibit signs or symptoms associated with infection, and that past infections can be reactivated following treatment with AUCATZYL - [see Warnings and Precautions (5.4) and Adverse Reactions (6) ]. Secondary Malignancies: Secondary malignancies, including T cell malignancies, have occurred following treatment with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies [see Boxed Warning , Warnings and Precautions (5.9), Adverse Reactions (6.3)]. Advise patients of the need to: Refrain from driving or operating heavy or potentially dangerous machinery for at least eight weeks after AUCATZYL infusion [see Warnings and Precautions (5.2) ]. Have periodic monitoring of blood counts. Contact Autolus Inc at 1-855-288-5227 if they are diagnosed with a secondary malignancy [see Warnings and Precautions (5.8) ] .
Spl medguide
Information about the patient medication guide that accompanies the drug product. Certain drugs must be dispensed with an accompanying medication guide. This field may contain information about when to consult the medication guide and the contents of the medication guide.MEDICATION GUIDE AUCATZYL ® [pronounced aw-kat-zil] (obecabtagene autoleucel) Read this Medication Guide before you start your AUCATZYL treatment. The more you know about your treatment, the more active you can be in your care. Talk with your healthcare provider if you have questions about your health condition or treatment. Reading this Medication Guide does not take the place of talking with your healthcare provider about your treatment. What is the most important information I should know about AUCATZYL? AUCATZYL may cause side effects that are life-threatening and can lead to death. Call or see your healthcare provider or get emergency help right away if you get any of the following: fever (100.4°F/38°C or higher) severe nausea, vomiting, diarrhea severe headache dizziness or light-headedness difficulty breathing confusion fast or irregular heartbeat low blood pressure chills/shivering shaking or twitching (tremor) It is important to tell your healthcare provider that you received AUCATZYL and to show them your AUCATZYL Patient Wallet Card. Your healthcare provider may give you other medicines to treat your side effects. What is AUCATZYL? AUCATZYL is a treatment for adults with acute lymphoblastic leukemia. It is used following disease progression while on or after other treatment. AUCATZYL is a medicine made from your own white blood cells, which have been changed (genetically modified) to recognize and attack your leukemic cells. Before getting AUCATZYL, tell your healthcare provider about all of your medical problems, including if you have or have had: Neurologic problems (such as seizures, stroke, new or worsening memory loss) Lung or breathing problems Heart problems A recent or active infection Past infections which can be reactivated following treatment with AUCATZYL Pregnancy, you think you may be pregnant, or plan to become pregnant Breastfeeding Tell your healthcare provider about all the medication you take, including prescription and over-the-counter medicines, vitamins, dietary supplements, and herbal supplements. How will I receive AUCATZYL? AUCATZYL is made from your own white blood cells, so your blood will be collected by a process called "leukapheresis" (loo-kah-fur-ee-sis), which will concentrate your white blood cells. Step 1: Your blood cells will be sent to a manufacturing center to make your AUCATZYL. While waiting for AUCATZYL to be made, you may get other medicines to stabilize your cancer. This is so that your acute lymphoblastic leukemia does not get worse. Within 7 days before you start treatment, a sample of your cells will be taken to confirm your disease burden, this will determine which infusion dose you are given first. Your infusion dose will be tailored to the burden of your disease. This will be provided as two separate infusions. Step 2: Before you receive AUCATZYL, your healthcare provider will give you chemotherapy for a few days to make room in the bone marrow. When your AUCATZYL is ready, your healthcare provider will give it to you through a catheter (tube) placed into your vein (intravenous infusion). After you receive your AUCATZYL first infusion you will receive your second infusion 10 days (± 2 days) later. 30 minutes before you are given AUCATZYL, you may be given medicines for fever (such as acetaminophen). Step 3: After AUCATZYL infusion, you will be monitored daily for at least fourteen days after the infusion so that your healthcare team can closely monitor your recovery. You should plan to stay close to the location where you received your treatment for at least four weeks after getting AUCATZYL. Your healthcare provider will help you with any side effects that may occur. You may be hospitalized for side effects. Your healthcare provider will determine when you can go home. Your healthcare provider will want to do blood tests to follow your progress. It is important that you do have your blood tested. If you miss an appointment, call your healthcare provider as soon as possible to reschedule. What should I avoid after receiving AUCATZYL? Do not drive, operate heavy machinery, or do other dangerous activities for eight weeks after you get AUCATZYL because the treatment can cause sleepiness, confusion, weakness, and temporary memory and coordination problems. Do not donate blood, organs, tissues, or cells for transplantation. What are the possible side effects of AUCATZYL? The most common side effects of AUCATZYL include: Fever (100.4°F/38°C or higher) Nausea Diarrhea Infections Headache Muscle or joint pain Fatigue or feeling very tired Low blood pressure (dizziness or light-headedness, headache, fatigue, short of breath) Fast irregular heartbeat Confusion Difficulty speaking or slurred speech Low white blood cells (can occur with a fever) Bleeding AUCATZYL may increase your risk of getting cancers including certain types of blood cancers. Your healthcare provider should monitor you for this. These are not all the side effects of AUCATZYL. Call your healthcare provider about any side effects that concern you. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of AUCATZYL. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like more information about AUCATZYL, talk with your healthcare provider. You can ask your healthcare provider for information about AUCATZYL that is written for health professionals. You can get additional information by contacting Autolus Inc at 1-855-288-5227 or at www.AUCATZYL.com What are the ingredients in AUCATZYL? Active ingredients : obecabtagene autoleucel Inactive ingredients : albumin (human); DMSO Manufactured by: Autolus Limited, Marshgate, Stevenage, SG1 1FR, United Kingdom. Manufactured for: Autolus Inc., Gaithersburg, MD, 20877 US License No 2339 AUCATZYL is a registered trademark of Autolus Limited. © 2024 Autolus Limited. All Rights Reserved. This Medication Guide has been approved by the U.S. Food and Drug Administration. Issued: 11/2024
| MEDICATION GUIDE AUCATZYL® [pronounced aw-kat-zil] (obecabtagene autoleucel) |
|---|
| Read this Medication Guide before you start your AUCATZYL treatment. The more you know about your treatment, the more active you can be in your care. Talk with your healthcare provider if you have questions about your health condition or treatment. Reading this Medication Guide does not take the place of talking with your healthcare provider about your treatment. |
AUCATZYL may cause side effects that are life-threatening and can lead to death. Call or see your healthcare provider or get emergency help right away if you get any of the following:
|
| It is important to tell your healthcare provider that you received AUCATZYL and to show them your AUCATZYL Patient Wallet Card. Your healthcare provider may give you other medicines to treat your side effects. |
|
|
|
|
|
|
|
| Manufactured by: Autolus Limited, Marshgate, Stevenage, SG1 1FR, United Kingdom. |
| Manufactured for: Autolus Inc., Gaithersburg, MD, 20877 |
| US License No 2339 |
| AUCATZYL is a registered trademark of Autolus Limited. |
| © 2024 Autolus Limited. All Rights Reserved. |
| This Medication Guide has been approved by the U.S. Food and Drug Administration. Issued: 11/2024 |
Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.14 CLINICAL STUDIES The efficacy of AUCATZYL was evaluated in an open-label, multi-center, single-arm study (FELIX study; NCT04404660). The study enrolled patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Eligible patients were adults with refractory ALL, first relapse following a remission lasting ≤ 12 months, relapsed or refractory ALL after two or more prior lines of systemic therapy, or relapsed or refractory ALL at least greater than 3 months after allogeneic stem cell transplantation (SCT) and had disease burden of ≥ 5% blasts in bone marrow at screening. The study excluded patients with isolated extra medullary disease, active or serious infections requiring systemic antimicrobials, active graft versus host disease, history or presence of CNS disorders. Treatment was administered in the in-patient setting and consisted of lymphodepleting chemotherapy (fludarabine 30 mg/m 2 IV daily for 4 days; cyclophosphamide 500 mg/m 2 IV daily for 2 days starting with first dose of fludarabine) followed by AUCATZYL as a split dose infusion with a total recommended dose of 410 × 10 6 CD19 CAR-positive viable T cells . A total of 112 patients were enrolled and underwent leukapheresis; 18 (16%) of whom discontinued without receiving AUCATZYL infusion due to the following: death (n=11), adverse event (n=1), physician decision (n=1), and manufacturing failure (n=5). Among the remaining 94 patients who received at least one infusion of AUCATZYL, 65 patients had ≥ 5% blasts in the bone marrow after screening and prior to the start of the lymphodepletion therapy, and received a conforming product, qualifying them as efficacy-evaluable patients. The population characteristics of efficacy-evaluable patients were as follows: median age was 51 years (range: 20 to 77 years) with 7 patients (11%) ≤ 25 years of age and 14 patients (22%) ≥ 65 years of age, 35 patients (54%) were female, 47 patients (72%) were White, 8 patients (12%) were Asian and 1 patient (2%) was Black or African American. Twenty-one patients (32%) were of Hispanic or Latino ethnicity. At enrollment, 35 patients (54%) were refractory to the last prior line of therapy, and 32 patients (49%) relapsed to first-line therapy within 12 months. The median number of prior lines of therapy was 2 (range: 1 to 6). Thirty-five patients (54%) received either blinatumomab or inotuzumab ozogamicin and 10 patients (15%) received both blinatumomab and inotuzumab ozogamicin, 22 (34%) patients received prior SCT therapy, 17 (26%) patients had Ph + ALL and 13 (20%) patients had extramedullary disease. Fifty-nine patients (91%) received bridging therapy between leukapheresis and lymphodepleting chemotherapy. The median dose was 410 × 10 6 CD19 CAR-positive viable T cells (range: 10 to 418 × 10 6 CD19 CAR-positive viable T cells). Fifty-eight patients (89%) received the target dose of 410 × 10 6 CD19 CAR-positive viable T cells (+/- 25%). Five patients (8%) only received the first dose, primarily due to adverse events (5%). The median time from leukapheresis to product release was 20 days (range: 17 to 23 days) and the median time from leukapheresis to AUCATZYL infusion was 35 days (range: 26 to 74 days). The major efficacy outcome measures were rate and duration of complete remission within 3 months after infusion. Additional outcome measures were rate and duration of overall complete remission which includes complete remission and complete remission with incomplete hematologic recovery, at any time. The efficacy results are summarized in Table 6: below. Table 6: Efficacy Results for FELIX Study Endpoint Efficacy Evaluable N=65 n (%) All Leukapheresed N=112 n (%) CI=confidence interval; NR=not reached. Complete Remission (within 3 months) rate n (%) 27 (42%) 40 (36%) [95% CI] (29%, 54%) (27%, 45%) Duration (months), median [95% CI] 14.1 (6.1, NR) 14.1 (6.2, NR) (Range in months) (0.5+, 21.2) (0.5+, 21.2) Overall Complete Remission (At Anytime) rate Rate of Overall Complete Remission "At Anytime" includes Complete Remission and Complete Remission with incomplete hematologic recovery "At Anytime". n (%) 41 (63%) 60 (54%) [95% CI] (50%, 75%) (44%, 63%) Duration (months), median [95% CI] 14.1 (6.2, NR) 14.1 (8.1, NR) (Range in months) (0.03+, 21.2) (0.03+, 21.2) Among patients in the efficacy evaluable population who achieved a best response of complete remission "At Anytime" (N=33; 51%), the median duration for remission was 14.1 months (95% confidence interval [CI]: 6.1, not reached [NR]). Among patients in the efficacy evaluable population in whom best response was complete remission with incomplete hematologic recovery "At Anytime" (N=8; 12%), the median duration of remission was 10.5 months (95% CI: 1.8, NR).
| Endpoint | Efficacy Evaluable N=65 n (%) | All Leukapheresed N=112 n (%) |
|---|---|---|
| CI=confidence interval; NR=not reached. | ||
| Complete Remission (within 3 months) rate | ||
| n (%) | 27 (42%) | 40 (36%) |
| [95% CI] | (29%, 54%) | (27%, 45%) |
| Duration (months), median [95% CI] | 14.1 (6.1, NR) | 14.1 (6.2, NR) |
| (Range in months) | (0.5+, 21.2) | (0.5+, 21.2) |
| Overall Complete Remission (At Anytime) rate | ||
| n (%) | 41 (63%) | 60 (54%) |
| [95% CI] | (50%, 75%) | (44%, 63%) |
| Duration (months), median [95% CI] | 14.1 (6.2, NR) | 14.1 (8.1, NR) |
| (Range in months) | (0.03+, 21.2) | (0.03+, 21.2) |
References
This field may contain references when prescription drug labeling must summarize or otherwise relay on a recommendation by an authoritative scientific body, or on a standardized methodology, scale, or technique, because the information is important to prescribing decisions.15 REFERENCES Lee DW et al (2019), ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr; 25(4):625-638.
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.8.5 Geriatric Use Of the 100 patients treated with AUCATZYL, 20 (20%) were 65 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger patients.
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 Pediatric Use The safety and efficacy of AUCATZYL have not been established in pediatric patients.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy Risk Summary There is limited available data with AUCATZYL use in pregnant women. In the FELIX study, one patient became pregnant 6 months following treatment with AUCATZYL. The patient had a premature delivery at 30 weeks of pregnancy. No animal reproductive and developmental toxicity studies have been conducted with AUCATZYL to assess whether AUCATZYL can cause fetal harm when administered to a pregnant woman. It is not known if AUCATZYL has the potential to be transferred to the fetus and cause fetal toxicity. Based on the mechanism of action of AUCATZYL, if the transduced cells cross the placenta, they may cause fetal toxicity, including B-cell lymphocytopenia and hypogammaglobinemia. Therefore, AUCATZYL is not recommended for women who are pregnant. Pregnancy after AUCATZYL infusion should be discussed with the treating physician. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There is limited available data with AUCATZYL use in pregnant women. In the FELIX study, one patient became pregnant 6 months following treatment with AUCATZYL. The patient had a premature delivery at 30 weeks of pregnancy. No animal reproductive and developmental toxicity studies have been conducted with AUCATZYL to assess whether AUCATZYL can cause fetal harm when administered to a pregnant woman. It is not known if AUCATZYL has the potential to be transferred to the fetus and cause fetal toxicity. Based on the mechanism of action of AUCATZYL, if the transduced cells cross the placenta, they may cause fetal toxicity, including B-cell lymphocytopenia and hypogammaglobinemia. Therefore, AUCATZYL is not recommended for women who are pregnant. Pregnancy after AUCATZYL infusion should be discussed with the treating physician. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. 8.2 Lactation Risk Summary There is no information regarding the presence of AUCATZYL in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for AUCATZYL and any potential adverse effects on the breastfed infant from AUCATZYL or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Pregnancy status of females with reproductive potential should be verified. Sexually active females of reproductive potential should have a negative pregnancy test before starting treatment with AUCATZYL. Contraception See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive lymphodepleting chemotherapy treatment. There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with AUCATZYL. Infertility There are no data on the effect of AUCATZYL on fertility. 8.4 Pediatric Use The safety and efficacy of AUCATZYL have not been established in pediatric patients. 8.5 Geriatric Use Of the 100 patients treated with AUCATZYL, 20 (20%) were 65 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger patients.
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16 HOW SUPPLIED/STORAGE AND HANDLING AUCATZYL 410 × 10 6 CD19 CAR-positive viable T cells NDC (83047-410-04) is supplied in three to five infusion bags (see below) containing a frozen suspension of genetically modified autologous T cells in PBS, HSA, EDTA and 7.5% DMSO. Each infusion bag of AUCATZYL is individually packed within an overwrap and then enclosed within a metal cassette. AUCATZYL is shipped from the manufacturing facility to the cellular therapy laboratory associated with the infusion center in a cryogenic shipper charged with liquid nitrogen. A Release for Infusion certificate is provided to the infusion site in the shipper and via the Autolus Scheduling Portal with the product. Infusion bag configurations Color Code Fill Volume Range (min – max) NDC Number 10 × 10 6 CD19 CAR-positive viable T cells in one 50mL infusion bag Blue 10 mL 83047-010-10 100 × 10 6 CD19 CAR-positive viable T cells in one or more 50mL infusion bags Orange 10 to 20 mL 83047-100-10 100 × 10 6 CD19 CAR-positive viable T cells in one 250mL infusion bag Orange 30 to 70 mL 83047-100-30 300 × 10 6 CD19 CAR-positive viable T cells in one or more 250mL infusion bags Red 30 to 70 mL 83047-300-30 Match the identity of the patient with the patient identifiers on the infusion bag upon receipt [see Dosage and Administration (2.3) ]. Store AUCATZYL frozen in the vapor phase of liquid nitrogen (below minus 150ºC) [see Dosage and Administration (Section 2.3) ]. Thaw AUCATZYL prior to infusion [see Dosage and Administration (2.3) ]. Do not re-freeze after thawing. Do not irradiate AUCATZYL, as this could lead to inactivation.
| Infusion bag configurations | Color Code | Fill Volume Range (min – max) | NDC Number |
|---|---|---|---|
| 10 × 106 CD19 CAR-positive viable T cells in one 50mL infusion bag | Blue | 10 mL | 83047-010-10 |
| 100 × 106 CD19 CAR-positive viable T cells in one or more 50mL infusion bags | Orange | 10 to 20 mL | 83047-100-10 |
| 100 × 106 CD19 CAR-positive viable T cells in one 250mL infusion bag | Orange | 30 to 70 mL | 83047-100-30 |
| 300 × 106 CD19 CAR-positive viable T cells in one or more 250mL infusion bags | Red | 30 to 70 mL | 83047-300-30 |
Storage and handling
Information about safe storage and handling of the drug product.Match the identity of the patient with the patient identifiers on the infusion bag upon receipt [see Dosage and Administration (2.3) ]. Store AUCATZYL frozen in the vapor phase of liquid nitrogen (below minus 150ºC) [see Dosage and Administration (Section 2.3) ]. Thaw AUCATZYL prior to infusion [see Dosage and Administration (2.3) ]. Do not re-freeze after thawing. Do not irradiate AUCATZYL, as this could lead to inactivation.
Boxed warning
Information about contraindications or serious warnings, particularly those that may lead to death or serious injury.WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, and SECONDARY HEMATOLOGICAL MALIGNANCIES Cytokine Release Syndrome (CRS), occurred in patients receiving AUCATZYL. Do not administer AUCATZYL to patients with active infection or inflammatory disorders. Prior to administering AUCATZYL, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage CRS [see Dosage and Administration (2.2 , 2.3) , Warnings and Precautions (5.1) ]. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), including fatal or life-threatening reactions, occurred in patients receiving AUCATZYL, including concurrently with CRS or after CRS resolution. Monitor for neurologic signs and symptoms after treatment with AUCATZYL. Prior to administering AUCATZYL, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage neurologic toxicities. Provide supportive care and/or corticosteroids, as needed [see Dosage and Administration (2.2 , 2.3) , Warnings and Precautions (5.2) ]. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies [see Warnings and Precautions (5.8) ]. WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, and SECONDARY HEMATOLOGICAL MALIGNANCIES See full prescribing information for complete boxed warning. Cytokine Release Syndrome (CRS), occurred in patients receiving AUCATZYL. Do not administer AUCATZYL to patients with active infection or inflammatory disorders. Prior to administering AUCATZYL, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage CRS. ( 2.2 , 2.3 , 5.1 ). Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) including fatal or life-threatening reactions, occurred in patients receiving AUCATZYL, including concurrently with CRS or after CRS resolution. Monitor for neurologic signs and symptoms after treatment with AUCATZYL. Prior to administering AUCATZYL, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage neurologic toxicities ( 2.2 , 2.3 , 5.2 ). T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies (5.9).
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API