The following Structured Product Label (SPL) was submitted to the FDA by Orca Biosystems Inc. for the product Tregzi (NDC 85866-223). This document serves as the official prescribing information, containing essential scientific data and clinical materials required for healthcare providers and patients.
This specific version of the label includes detailed information regarding 1 indications and usage, 2.1 dose, 2.2 preparation and administration, 3 dosage forms and strengths, 4 contraindications, 5.1 graft failure, 5.2 graft-versus-host disease, 5.3 infusion reactions, and other regulatory disclosures. Use the navigation below to review specific sections of the FDA submission.
TREGZI is indicated for use in matched donor hematopoietic stem cell transplantation with myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease-free survival, in the treatment of adults with hematological malignancies.
For intravenous use only.
A single dose of TREGZI consists of hematopoetic stem and progenitor cells (HSPCs), regulatory T cells (Tregs), conventional T cells (Tcons), and Tcon diluent provided in 4 separate infusion bags labeled for the specific patient. Each patient-specific infusion bag of TREGZI contains a batch-dependent concentration of allogeneic cells (see Table 1). Patient-specific dose information can be found within the Certificate of Analysis (COA).
| Component | Dose Regimen | Target Viable Cell Dose Range (Cells per Patient kg) |
|---|---|---|
| Abbreviations: HSPCs, hematopoietic stem and progenitor cells; Tregs, regulatory T cells; Tcons, conventional T cells. | ||
| HSPCs | Intravenous, once, on day 0 | ≥1.0 × 106 |
| Tregs | Intravenous, once, on day 0 immediately after administration of HSPCs | 1.3 × 106 to 3.5 × 106 |
| Tcons | Intravenous, once, on day +2 to +3 (after the start of HSPC infusion on day 0) | 1.3 × 106 to 6.9 × 106 |
| Tcon diluent | Intravenous, once, administered with Tcons drug product on day +2 to +3 (after HSPC infusion on day 0) | 30 mL |
Preparing Patient for TREGZI Infusion
Pretreatment
Receipt of TREGZI
Do not irradiate.
TREGZI is shipped directly to the treatment center in two transport containers [See How Supplied/Storage and Handling (16)]:
Upon receipt of the refrigerated cardboard shipping container containing the HSPC and Treg carton and infusion bags:
Upon receipt of the cardboard box containing the (1) Tcon metal cassette and infusion bag and (2) Tcon diluent carton and infusion bag:
Premedication
Day 0: Preparation and Administration of TREGZI HSPCs and Tregs
Day 0: Preparation of HSPCs and Tregs for Infusion
Day 0: Administration of HSPCs and Tregs
Do NOT use a leukodepleting filter.
Day +2 to Day +3: Preparation and Administration of TREGZI Tcons
Day +2 to Day +3: Preparation - Thawing of Tcons
Preparation of the Tcons for infusion occurs on day +2 to +3 after the start of HSPC infusion on day 0.
Day +2 to Day +3: Preparation - Dilution of Tcons with Tcon Diluent
Day +2 to Day +3: Administration of Tcons
DO NOT use a leukodepleting filter.
TREGZI contains human blood cells. Follow universal precautions and local biosafety guidelines for handling and disposal to avoid potential transmission of infectious diseases.
TREGZI is a cell suspension for intravenous infusion. TREGZI is provided in separate infusion bags labeled for the specific patient. Each single-dose, patient-specific infusion bag of TREGZI contains a batch-dependent concentration of allogeneic cells as described in Table 2. Patient-specific dose information can be found within the COA.
| Cell Component | Target Viable Cell Dose Range (Cells per Patient kg) | Excipients | Appearance | Container and Approximate Fill Volume | Component Identifying Information |
|---|---|---|---|---|---|
| Abbreviations: DMSO, dimethyl sulfoxide; HSA, human serum albumin; HSPCs, hematopoietic stem and progenitor cells; MEI, multiple electrolytes injection; Tcons, conventional T cells; Tregs, regulatory T cells. | |||||
| HSPCs | ≥1.0 × 106 | MEI, Type 1 HSA | Clear to opaque liquid Color = off-white, white, yellow, orange, to red | Fill volume: approximately 100 mL | Orange colored label specifying "Step 1 of Administration" |
| Tregs | 1.3 × 106 to 3.5 × 106 | MEI, Type 1 HSA | Clear to opaque liquid Color = off-white, white, yellow, orange, to red | Fill volume: approximately 100 mL | Light blue colored label specifying "Step 2 of Administration" |
| Tcons | 1.3 × 106 to 6.9 × 106 | MEI, Type 1, HSA, DMSO Hetastarch (6% hetastarch in 0.9% sodium chloride injection added at 30.5% (v/v)). | Clear to opaque liquid Color = off-white, white, yellow, orange, to red | Fill volume: approximately 15 mL | Dark blue colored label specifying "Step 3a of Administration" |
| Diluent | |||||
| Tcon Diluent | Not Applicable | MEI Type 1, HSA | Clear Color: Colorless to yellow | Fill volume: approximately 38 mL | Tan label specifying "Step 3b of Administration" |
None.
Graft failure has occurred after TREGZI administration [see Adverse Reactions (6.1)]. Screen TREGZI recipients for antidonor antibodies that may prevent engraftment. Monitor patients closely for laboratory evidence of hematopoietic recovery.
Acute and chronic Graft-Versus-Host disease (GVHD), including life-threatening and fatal cases, occurred following treatment with TREGZI [see Adverse Reactions (6.1)]. Acute GVHD manifests as maculopapular rash, gastrointestinal symptoms, and elevated bilirubin. Chronic GVHD may include skin rash, mouth sores, dry eyes, liver inflammation, and development of scar tissue in the skin and joints and damage to the lungs. Treat patients with a single agent calcineurin inhibitor as prophylaxis to decrease the risk of GVHD. Monitor for signs and symptoms of GVHD, and treat if GVHD develops.
Infusion reactions (IRs) may occur during or following treatment with TREGZI. Serious hypersensitivity reactions including anaphylaxis may occur due to DMSO, human serum albumin (HSA), Dextran or murine protein present in TREGZI. IRs may begin within minutes of the start of TREGZI infusion, although symptoms may continue to intensify and not peak for several hours after the completion of the infusion. Monitor patients for signs and symptoms of IRs during and after TREGZI administration. When a reaction occurs, pause the infusion and institute supportive care as needed. Premedicate patients with antipyretics and histamine antagonists prior to infusion to reduce the incidence and intensity of infusion reactions.
Secondary malignancies and malignancies of donor origin may occur following treatment with TREGZI [see Adverse Reactions (6.1)]. Development of secondary malignancies, including posttransplantation lymphoproliferative disorder (PTLD) may occur many years after transplantation. PTLD manifests as a lymphoma-like disease favoring non-nodal sites. PTLD is usually fatal if not treated. Serial monitoring of blood for EBV DNA may be warranted in patients with persistent cytopenias. No patient treated with TREGZI has developed PTLD. Monitor for malignancies of donor origin and secondary malignancies.
Contact Orca Bio at 1-877-290-6722 if any patient is diagnosed with a secondary malignancy or a malignancy of donor origin.
Transmission of serious infectious or communicable disease or agents may occur with TREGZI treatment as it is derived from human donor blood and manufactured using animal-derived reagents. Risks of transmission of infectious agents may occur despite screening or testing of donors. Risks of transmission of serious infections include, but are not limited to, human immunodeficiency virus, human T cell lymphotropic virus (HTLV)-1 and -2, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, Trypanosoma cruzi, West Nile virus (WNV), cytomegalovirus, transmissible spongiform encephalopathy agents and vaccinia. Monitor patients for signs and symptoms of infections, perform tests for infectious agents and treat as clinically indicated.
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 data described in this section reflects exposure to TREGZI in one clinical study (Precision-T Study) which enrolled patients with advanced hematologic malignancies eligible for HLA-matched allogeneic stem cell transplantation following myeloablative preparative regimen. The study treated 88 patients with TREGZI and 94 patients with standard of care (SoC) unmanipulated graft. The patients were followed for a duration of 24 months [see Clinical Studies (14)].
Serious adverse reactions within the first 100 days occurred in 25 patients (28%) treated with TREGZI including bacterial infections (n=12; 14%), pyrexia (n=4; 5%), venooclusive liver disease (n=3; 3%), and viral infections (n=3; 3%). Fatal adverse reactions occurred in 3 patients (3%).
Non-relapse deaths at 12 months occurred in 3/88 (3.4%) patients in the TREGZI group and in 11/94 (11.7%) patients in the SoC control group [see Clinical Studies (14)].
In the TREGZI treated safety population, the most common (greater than or equal to 10%) Grade 3 or 4 nonlaboratory adverse reactions were mucositis (28%), bacterial infection (18%), infection – pathogen unspecified (18%), and viral infection (14%).
Table 3 summarizes the most common nonlaboratory adverse reactions occurring in ≥10% patients treated with TREGZI or unmanipulated allograft control group in Precision-T Study.
| Adverse Reactions | TREGZI (N = 88) | SoC Control (N=94 ) | ||
|---|---|---|---|---|
| All Grades % | Grade 3 or Higher % | All Grades % | Grade 3 or Higher % | |
| Infections and infestations Infections and infestations were calculated for the first 2 years after transplantation. | ||||
| Abbreviations: GVHD, Graft-Versus-Host disease. | ||||
| Viral infections | 51 | 14 | 47 | 19 |
| Infections - pathogen unspecified | 45 | 18 | 56 | 30 |
| Bacterial infections | 40 | 18 | 38 | 16 |
| Fungal infections | 20 | 3 | 18 | 0 |
| Gastrointestinal disorders | ||||
| Diarrhea includes multiple related terms | 69 | 1 | 79 | 6 |
| Abdominal pain | 45 | 0 | 54 | 1 |
| Vomiting | 44 | 1 | 35 | 0 |
| Nausea | 41 | 1 | 44 | 2 |
| Immune system disorders | ||||
| Acute graft-versus-host disease Acute GVHD graded by MAGIC standardization criteria (Harris 2016) as determined by an independent review committee; calculated for the first year after transplantation. | 38 | 6 | 46 | 15 |
| General disorders and administration site conditions | ||||
| Mucositis | 85 | 28 | 88 | 37 |
| Edema | 30 | 0 | 38 | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Pneumonia | 5 | 5 | 17 | 15 |
| Skin and Subcutaneous Tissue Disorders | ||||
| Rash | 65 | 0 | 55 | 0 |
| Vascular Disorders | ||||
| Hemorrhage | 39 | 6 | 33 | 1 |
Other clinically important adverse reactions that occurred in less than 10% of patients treated with TREGZI include the following:
Table 4 summarizes the most common Grade 3 or 4 laboratory abnormalities occurring in ≥10% of patients in Precision-T Study.
Laboratory Abnormalities
| Laboratory Abnormality Includes lab abnormalities for the first 100 days ,Baseline lab values were assessed prior to conditioning regimen. Denominators ranged from 79 to 87 for TREGZI arm and 90 to 93 for Control arm for lab tests, based on the number of patients with a baseline value and at least one post treatment value for each lab test. | TREGZI Grade 3 or 4 % | SoC Control Grade 3 or 4 % |
|---|---|---|
| Lymphocyte count decreased | 98 | 94 |
| Platelet count decreased | 93 | 96 |
| Leukocyte count decreased | 89 | 89 |
| Neutrophil count decreased | 77 | 83 |
| Hemoglobin decreased | 71 | 81 |
| Alanine aminotransferase increased | 12 | 7 |
Risk Summary
There are no available data on TREGZI use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with TREGZI to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known if TREGZI has the potential to be transferred to the fetus. TREGZI should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Report all pregnancies following treatment with TREGZI to Orca Bio at 1-877-290-6722.
In the United States (U.S.) general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Risk Summary
There are no available data on the presence of TREGZI in human milk, the effect on the breastfed infant, or the effects on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TREGZI and any potential adverse effects on the breastfed infant from TREGZI or from the underlying maternal condition.
Pregnancy Testing
Females of reproductive potential should have a pregnancy test prior to starting the conditioning regimen for TREGZI.
Contraception
There are insufficient exposure data to provide a recommendation concerning the duration of contraception following treatment with TREGZI. See the prescribing information of selected myeloablative regimens for recommendations on use of contraception.
Infertility
There are no data on the effect of TREGZI on fertility.
Safety and efficacy of TREGZI in pediatric patients have not been established.
Although Precision-T Study did not include any patients aged 65 years and older, some patients over 65 years of age participated in other TREGZI studies using a myeloablative or reduced intensity conditioning (RIC) regimen. However, the number of patients was inadequate to allow subgroup analysis to support recommendations in the geriatric population.
TREGZI (allogeneic regulatory T cell immunotherapy with HSPC and T cells-vldq) is an allogeneic hematopoietic stem cell and T-cell immunotherapy isolated from the mobilized peripheral blood of an 8/8 HLA-matched related or unrelated donor and is donor- and recipient-specific.
TREGZI is composed of individual cell suspensions for intravenous infusion of 1) purified hematopoietic stem and progenitor cells (HSPCs), 2) regulatory T cells (Tregs), and 3) conventional T cells (Tcons). In addition, 4) a chemically defined diluent is provided to dilute the Tcons before infusion.
The HSPC, Treg and Tcon suspensions must pass a rapid microbial detection test prior to administration. Complete sterility test results are available approximately 14-days post-administration. The Tcon diluent must pass a sterility test before release for shipment.
TREGZI is isolated from the mobilized peripheral blood of a donor HLA-matched to the recipient, and administered after appropriate cytoreductive conditioning. TREGZI contains purified regulatory T cells (Tregs) and conventional T cells (Tcons). The exact mechanism by which Tregs exert their effects is not fully understood. Tregs are administered prior to Tcons to control GVHD and promote immune reconstitution. Nonclinical studies have shown that Tregs suppress Tcon activation and proliferation in secondary lymphoid organs and GVHD target organs, and improve immune reconstitution without compromising graft-versus-tumor (GVT) effects of Tcons. The immunosuppressive activity of Tregs occurs through various immunoregulatory mechanisms, which help preserve immune function and decrease severity of GVHD. Tcons are administered approximately two days later to accelerate immune reconstitution, characterized by the complete or partial restoration of peripheral blood T-cell counts. Immune reconstitution is thought to result in graft-versus-infection and graft-versus-leukemia effects.
TREGZI also contains allogeneic hematopoietic stem and progenitor cells (HSPCs). HSPCs home to the bone marrow, engraft, self-renew, proliferate, and differentiate into all mature blood cells. The mature cells are released from the bone marrow, circulate in the blood stream, and migrate to tissue sites, restoring blood counts and hematopoietic function.
No studies have been conducted to evaluate the pharmacodynamics of TREGZI.
No studies have been conducted to evaluate the pharmacokinetics of TREGZI.
No nonclinical studies were performed to evaluate the effect of TREGZI on carcinogenesis, mutagenesis, or impairment of fertility.
The efficacy of TREGZI was evaluated in a multicenter, open-label, randomized, controlled study (Phase 3 Precision-T Study; NCT05316701). The study enrolled adult patients with 1) acute leukemias (acute lymphoblastic leukemia [ALL], acute myelogenous leukemia [AML], or mixed phenotype/ undifferentiated) in complete remission (CR) or CR with incomplete recovery (CRi) or 2) myelodysplastic syndrome (MDS): i) with ≤10% blast burden in the bone marrow and who were eligible for allogeneic transplant per 2017 International Expert Panel recommendations1 including high-risk IPSS-R≥5, or poor risk genetic features, or failed nontransplant therapies including erythropoietin-stimulating agents (ESAs), lenalidomide, hypomethylating agents (HMAs), or intensive chemotherapies or ii) therapy-related/secondary MDS as defined by the World Health Organization (WHO) classification of myeloid malignancies. Patients with prior history of allogeneic hematopoietic stem cell transplantation were excluded.
In total, 187 patients were randomized to receive either TREGZI (n=93) in the treatment group or an unmanipulated allograft in the control group (n=94). Of the 93 patients randomized to TREGZI, 88 patients were treated with TREGZI. The reasons for not receiving TREGZI were as follows: One patient received cryopreserved SoC alloHCT because of COVID, 2 patients withdrew consent prior to treatment, 1 patient relapsed and did not enter remission, and 1 patient received TREGZI after the data cutoff date. The median (min, max) time from randomization to transplant is 9 days (6, 26) for patients who received TREGZI (N=88) and 8 days (6, 24) for patients who received SoC (N=94). Both TREGZI and the unmanipulated allograft were derived from G-CSF-mobilized peripheral blood apheresis product from 8/8 (at alleles A, B, C, and DRB1) HLA-matched sibling donors (MSD) or unrelated donors (MUD) and were administered after a myeloablative preparative regimen such as total body irradiation (TBI)-based or chemotherapy-based options. Patients in the TREGZI group received HSPC and Treg components on Day 0, Tcon component on Day 2 or 3 (if no evidence of uncontrolled bacterial, viral, or fungal infection and Karnofsky performance score ≥30%) and tacrolimus within 12 hours after T con infusion as GVHD prophylaxis. Patients in the control group received unmanipulated allograft on Day 0 and tacrolimus starting on Day-3 and methotrexate starting on Day 1 as GVHD prophylaxis.
The population demographics and characteristics were as follows: The median age was 44 years (range: 19 to 65 years), 103 patients (55%) were male, 139 patients (74%) were white, 18 patients (10%) were Asian, 3 patients (2%) were black, 3 patients (2%) American Indian or Alaskan Native, 2 patients (1%) were Native Hawaiian or Other Pacific Islander, and 22 patients (12%) had race not reported. The primary disease diagnoses were as follows: 57 patients (31%) with ALL, 100 patients (54%) with AML, 23 patients (12%) with MDS, and 7 patients (4%) with mixed phenotype acute leukemia (MPAL). Patients received the following myeloablative preparative regimen: 58 patients (31%) received TBI-based conditioning regimens, 126 (67%) received Busulfan-Fludarabine -Thiotepa conditioning regimens, 3 patients (2%) did not receive any conditioning regimen and treatment. DRI score was high in 36 patients (19%) and intermediate in 151 patients (81%). Baseline HCT-CI score were as follows: 45 patients (24%) were with score 0, 90 patients (48%) were with score 1-2, and 52 patients (28%) were with score 3-5. Ninety-five patients (51%) received a graft from 8/8 HLA matched sibling and 92 patients (49%) received a graft from 8/8 HLA matched unrelated donor. The demographics, disease characteristics, conditioning regimens, DRI score, HCT-CI score, and graft source were balanced between TREGZI group and the control group.
The primary efficacy endpoint was cGVHD-free survival (cGFS), defined as the time from HCT to death by any cause or moderate to severe cGVHD, as graded per National Institutes of Health [NIH] consensus criteria and determined by an independent review committee. To control the Type I error rate, other efficacy endpoints were tested in the following hierarchical order: time to moderate/severe chronic GVHD (cGVHD), overall survival (OS), and GVHD-free/relapse-free survival (GRFS).
The study demonstrated a statistically significant improvement in cGFS and time to moderate/severe cGVHD in patients randomized to TREGZI compared with patients randomized to control. Table 5 and Figure 1 below summarize the efficacy results from Precision-T Study.
| Endpoint | TREGZI (N = 93) Four subjects randomized to the TREGZI group did not receive treatment and were censored at Day 1. One subject randomized to the TREGZI group received cryopreserved SoC alloHCT and was analyzed according to the randomized treatment assignment. | SoC Control (N = 94) | Comparison | |
|---|---|---|---|---|
| Abbreviations: cGFS, cGVHD-free survival; cGVHD, chronic graft-versus-host disease; CI, confidence interval; DRI, Disease Risk Index; EAC, endpoint adjudication committee, HLA, human leukocyte antigen; MSD, matched sibling donor; MUD, matched unrelated donor; NE, not estimable. NIH, National Institutes of Health; SoC, standard of care. | ||||
| cGFS Stratified log-rank test was used to compare cGFS per EAC between the TREGZI group and the control group | ||||
| Number (%) of patients with events | 14 (15.1%) | 44 (46.8%) | ||
| Median, months [95% CI] | NE [NE, NE] | 7.3 [6.3, 15.5] | ||
| P value (log-rank) | <.00001 | |||
| Hazard Ratio Based on a stratified Cox proportional hazards model [95% CI] | 0.26 [0.14, 0.47] | |||
| Time to moderate or severe cGVHD Stratified Gray's test was used to compare time to moderate or severe cGVHD per EAC between the TREGZI group and the control group, treating death as a competing risk. An event for this time-to-event endpoint was defined as the first occurrence of moderate to severe cGVHD per NIH consensus criteria. Patients were followed for cGVHD for 2 years post transplant. | ||||
| Number (%) of patients with events | 7 (7.5%) | 30 (31.9%) | ||
| Cumulative Incidence % at 12 months [95% CI] | 12.6 [5.3, 23.1] | 44.0 [31.3, 56.1] | ||
| P value (Gray's test) | .00002 | |||
| Hazard Ratio Based on a stratified subdistribution proportional hazards model | 0.19 [0.08, 0.43] | |||
Figure 1: Kaplan-Meier Curve of cGFS in Precision-T Phase 3 (Intention-to-Treat Analysis Set)
Figure 1 (Tregzi 01)
The median duration of follow up was 8.48 (range: 0 to 22.2) months on the TREGZI arm and 9.03 (range: 0 to 20.3) months on the control arm.
At 12 months, the Kaplan-Meier estimate of cGFS was 78.0% (95% CI: 65.0%, 86.6%) for TREGZI compared with 38.4% (95% CI: 26.2%, 50.5%) for the control group.
Seven patients (7.5%) in the TREGZI group and 15 patients (16.0%) in the control group died on study with a median follow-up for survival of 11.04 (range: 0.2 to 23.9) months and 11.47 (range: 0.7 to 24.3) months, respectively.
Fifteen patients (16.1%) in the TREGZI group and 10 patients (10.6%) in the control group relapsed on study.
All 88 patients (100%) treated with TREGZI achieved a neutrophil count of 500/mm3 within 28 days of infusion. Of these, 53 patients (60.2%) had neutrophil counts greater than 500/mm3 on three consecutive days, confirming neutrophil recovery within 28 days of infusion.
Myeloid-lineage donor chimerism data were available for 68 of 88 patients treated with TREGZI. Among these 68 patients, all demonstrated myeloid-lineage donor chimerism >95% at Day +28 post-transplant.
1 de Witte T, Bowen D, Robin M, et al. Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel. Blood. 2017;129(13):1753-1762. doi:10.1182/blood-2016-06-724500
TREGZI (NDC-85866-223-04) is provided as a single dose and intended for use by a single patient.
TREGZI is provided in two transport containers:
| Bag (Container) and Carton (Package) Name | NDC |
|---|---|
| TREGZI (all components, located on Certificate of Analysis) | NDC 85866-223-04 |
| HSPC Infusion Bag Label | NDC 85866-124-01 |
| Treg Infusion Bag Label | NDC 85866-125-01 |
| Tcon Infusion Bag Label | NDC 85866-126-01 |
| Tcon Diluent Infusion Bag Label | NDC 85866-127-01 |
| Carton for Treg and HSPC | NDC 85866-123-02 |
| Cassette Label for Tcon | NDC 85866-126-02 |
| Carton for Tcon Diluent | NDC 85866-127-02 |
Refrigerated TREGZI HSPCs and Tregs
The HSPCs and Tregs are shipped at 2°C to 8°C (36°F to 46°F). The HSPCs and Tregs are in separate infusion bags labeled for a specific patient. The HSPC and Treg infusion bags are provided together in one protective carton, also labeled for a specific patient.
Cryopreserved TREGZI Tcons
The Tcons are shipped frozen in vapor phase of liquid nitrogen at below -125°C (below -193°F). The Tcon infusion bag is contained in an overwrap bag packed in a protective metal cassette. Both the Tcon infusion bag and cassette are labeled for a specific patient. The infusion bag label can not be observed when packaged in the protective metal cassette.
Do NOT open the Tcon metal cassette upon receipt. Only open the metal cassette immediately prior to thawing.
TREGZI Tcon diluent
The Tcon diluent is shipped at ambient temperature (20°C to 25°C, 68°F to 77°F). The Tcon diluent infusion bag is packaged in a protective carton. Both the infusion bag and carton are labeled for a specific patient.
Do NOT directly infuse the Tcon diluent into the patient.
Discuss the following with the patient receiving TREGZI.
Each TREGZI unit is specific to each patient. The course of therapy for TREGZI is three cell components for infusion, which is provided by the manufacturer as 4 separate infusion bags comprising the HSPCs, Tregs, Tcons, and Tcon diluent. Two infusions, HSPCs and Tregs, will take place on day 0 and one infusion, Tcons, on day +2 to +3 (after the start of HSPC infusion on day 0).
Prior to treatment, advise patients of the following:
Graft Failure
Advise patients that primary graft failure, which may be fatal, can occur [see Warnings and Precautions (5.1)].
Graft-Versus-Host Disease
Treat patients with a single agent calcineurin inhibitor as prophylaxis to decrease the risk of GVHD. Monitor for signs and symptoms of GVHD, and treat if GVHD develops. Report immediately any signs and symptoms suggestive of GVHD, including rash, joint pain, diarrhea, or yellowing of the eyes [see Warnings and Precautions (5.2)].
Infusion Reactions
Report immediately any signs and symptoms of Infusion reactions that occur within 24 hours of infusion of TREGZI including fever, chills, flushing, fatigue, shortness of breath, and dizziness/lightheadedness [see Warnings and Precautions (5.3)].
Secondary Malignancies and Malignancies of Donor Origin
Advise patients of the need to contact Orca Bio at 1-877-290-6722 if they are diagnosed with a secondary malignancy or malignancies of donor origin after treatment with TREGZI [see Warnings and Precautions (5.4).
Transmission of Infectious Agents
Advise patients of the risk of transmission of infectious disease [see Warnings and Precautions (5.5)].
Manufactured by:
Orca Biosystems, Inc.
7910 Metro Air Parkway
Sacramento, CA 95837
U.S. license number: 2404
v1
allogeneic regulatory T cell immunotherapy
with HSPC and T cells-vldq
TREGZI™
Step
1
NDC 85866-124-01
Step 1 of Administration: HSPC Component
Cell suspension for infusion
Rx Only
For allogeneic and intravenous use
Contains ≥ 1.0 x 106 viable cells per
kg in 100 mL of multiple electrolytes
injection (Type 1) and 2% HSA.
Store at 2°C to 8°C (36°F to 46°F).
DO NOT IRRADIATE. DO NOT FREEZE.
Infuse prior to the expiry time.
orcabio
Manufactured by: Orca Biosystems, Inc.
Menlo Park, CA 94025
1-877-411-ORCA (6722)
www.tregziHCP.com
U.S. Lic. # 2404
1341
Dosage: Infuse total HSPC Component
(Step 1). See package insert for
full dosage and administration
instructions.
Recipient: Last Name, First Name
Recipient DOB: YYYY-MMM-DD
Orca Patient ID: 00000000
Hospital Patient ID: 0000000000
EXP: YYYY-MMM-DD 00:00 UTC
[+/-] 00:00 PST
LOT: L-0000000000
DIN: W000000000000
Principal Display Panel (100 mL Bag Label)
allogeneic regulatory T cell immunotherapy
with HSPC and T cells-vldq
TREGZI™
Step
2
NDC 85866-125-01
Step 2 of Administration: Treg Component
Cell suspension for infusion
Rx Only
For allogeneic and intravenous use
Contains 1.3 x 106 to 3.5 x 106 viable
cells per kg in 100 mL of multiple
electrolytes injection (Type 1) and
2% HSA.
Store at 2°C to 8°C (36°F to 46°F).
DO NOT IRRADIATE. DO NOT FREEZE.
Infuse prior to the expiry time.
orcabio
Manufactured by: Orca Biosystems, Inc.
Menlo Park, CA 94025
1-877-411-ORCA (6722)
www.tregziHCP.com
U.S. Lic. # 2404
1340
Dosage: Infuse total Treg Component
(Step 2) immediately following
infusion of HSPC Component (Step 1).
See package insert for full dosage and
administration instructions.
Recipient: Last Name, First Name
Recipient DOB: YYYY-MMM-DD
Orca Patient ID: 00000000
Hospital Patient ID: 0000000000
EXP: YYYY-MMM-DD 00:00 UTC
[+/-] 00:00 PST
LOT: L-0000000000
DIN: W000000000000
Principal Display Panel (100 mL Bag Label)
NDC 85866-123-02
allogeneic regulatory T cell immunotherapy
with HSPC and T cells-vldq
TREGZI™
Cell suspension for infusion
For allogeneic and intravenous use
Rx Only
Carton contains a single dose of: 1 bag of HSPC Component and 1 bag of Treg Component.
1 STEP 1 HSPC Component
Contains ≥ 1.0 x 106 viable cells
per kg in 100 mL of multiple
electrolytes injection (Type 1)
and 2% HSA.
HSPC
Component
2 STEP 2 Treg Component
Contains 1.3 x 106 to 3.5 x 106
viable cells per kg in 100 mL of
multiple electrolytes injection
(Type 1) and 2% HSA.
Treg
Component
VERIFY PATIENT ID
Dosage: Infuse total HSPC Component (Step 1). Immediately following infusion
of HSPC Component, infuse total Treg Component (Step 2). See package insert for
full dosage and administration instructions.
See Certificate of Analysis for patient-specific dose.
Principal Display Panel (HSPC and Treg Bag Carton)
allogeneic regulatory T cell immunotherapy
with HSPC and T cells-vldq
TREGZI™
Step
3a
NDC 85866-126-01
Step 3a of Administration: Tcon Component
Cell suspension for infusion
Rx Only
For allogeneic and intravenous use after dilution
Contains 1.3 x 106 to 6.9 x 106 viable cells per kg
cryopreserved in 15 mL of multiple electrolytes
injection (Type 1), 3-4% HSA, 7.5% DMSO,
1.8% Hetastarch, and Sodium Chloride Injection.
Store at ≤ -125°C in vapor phase of liquid nitrogen.
DO NOT IRRADIATE. DO NOT REFREEZE.
Thaw immediately before use. Dilute with 30 mL
Tcon Diluent, for a final volume of 45 mL.
Hold at 2°C to 8°C (36°F to 46°F).
orcabio
Manufactured by: Orca Biosystems, Inc.
Menlo Park, CA 94025
1-877-411-ORCA (6722)
www.tregziHCP.com
U.S. Lic. # 2404
1342
Dosage: On Day 2+ to 3+ after infusion of HSPC
Component (Step 1) and Treg Component
(Step 2), add Tcon Diluent (Step 3b) to Tcon
Component (Step 3a). Infuse total diluted Tcon
Component. See package insert for full dosage
and administration instructions.
Recipient: Last Name, First Name
Recipient DOB: YYYY-MMM-DD
Orca Patient ID: 00000000
Hospital Patient ID: 0000000000
EXP: YYYY-MMM-DD 00:00 UTC
[+/-] 00:00 PST
LOT: L-0000000000
DIN: W000000000000
Principal Display Panel (15 mL Bag Label)
allogeneic regulatory T cell immunotherapy
with HSPC and T cells-vldq
TREGZI™
Step
3a
NDC 85866-126-02
Step 3a of Administration: Tcon Component
Cell suspension for infusion
Rx Only
For allogeneic and intravenous use after dilution
Contains 1.3 x 106 to 6.9 x 106 viable cells per kg
cryopreserved in 15 mL of multiple electrolytes
injection (Type 1), 3-4% HSA, 7.5% DMSO,
1.8% Hetastarch, and Sodium Chloride Injection.
No U.S. Standard of Potency
Store at ≤ -125°C in vapor phase of liquid nitrogen.
DO NOT IRRADIATE. DO NOT REFREEZE.
Thaw immediately before use. Dilute with 30 mL
Tcon Diluent, for a final volume of 45 mL.
Hold at 2°C to 8°C (36°F to 46°F).
orcabio
Manufactured by: Orca Biosystems, Inc.
Menlo Park, CA 94025
1-877-411-ORCA (6722)
www.tregziHCP.com
U.S. Lic. # 2404
1378
Dosage: On Day 2+ to 3+ after infusion of HSPC
Component (Step 1) and Treg Component
(Step 2), add Tcon Diluent (Step 3b) to Tcon
Component (Step 3a). Infuse total diluted Tcon
Component. See package insert for full dosage
and administration instructions.
VERIFY PATIENT ID
Recipient: Last Name, First Name
Recipient DOB: YYYY-MMM-DD
Orca Patient ID: 00000000
Hospital Patient ID: 0000000000
EXP: YYYY-MMM-DD 00:00 UTC
[+/-] 00:00 PST
LOT: L-0000000000
DIN: W000000000000
Principal Display Panel (15 mL Casette Label)
allogeneic regulatory T cell immunotherapy
with HSPC and T cells-vldq
TREGZI™
Step
3b
NDC 85866-127-01
Step 3b of Administration: Tcon Diluent
For intravenous use
Rx Only
Use only for diluting TREGZI™ Tcon
Component (Step 3a).
Single-use bag
Contains 38 mL sterile multiple electrolytes
injection (Type 1) and 2% HSA.
Store at 15°C to 30°C (59°F to 86°F).
DO NOT FREEZE.
Transfer to 2°C to 8°C (36°F to 46°F) for
at least 30 minutes prior to use.
Discard unused portion.
orcabio
Manufactured by: Orca Biosystems, Inc.
Menlo Park, CA 94025
1-877-411-ORCA (6722)
www.tregziHCP.com
U.S. Lic. # 2404
1343
Dosage: Add Diluent (Step 3b) to Tcon
Component (Step 3a). See package
insert for full dosage and administration
instructions.
Recipient: Last Name, First Name
Recipient DOB: YYYY-MMM-DD
Orca Patient ID: 00000000
Hospital Patient ID: 0000000000
See label on back of bag for lot
information and expiration date.
Principal Display Panel (38 mL Bag Label)
NDC 85866-127-02
allogeneic regulatory T cell immunotherapy
with HSPC and T cells-vldq
TREGZI™
Step 3b of Administration: Tcon Diluent
For intravenous use
Use only for diluting TREGZI™ Tcon
Component (Step 3a).
Single-use bag
Contains 38 mL sterile multiple
electrolytes injection (Type 1) and
2% HSA.
Store at 15°C to 30°C (59°F to 86°F).
DO NOT FREEZE.
Transfer to 2°C to 8°C (36°F to 46°F) for
at least 30 minutes prior to use.
Discard unused portion.
No preservative
No U.S. Standard of Potency
Dosage: Add Diluent (Step 3b) to
Tcon Component (Step 3a). See
package insert for full dosage and
administration instructions.
Rx Only
Step
3b
Tcon
Diluent
Carton contains 1 bag
of Tcon Diluent.
VERIFY PATIENT ID
Principal Display Panel (38 mL Bag Carton)
* Please review the disclaimer below.
