Efbemalenograstim alfa

12.1 Mechanism of Action Efbemalenograstim alfa-vuxw is a colony-stimulating factor that acts on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation.

1. INDICATIONS AND USAGE RYZNEUTA is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. Limitations of Use RYZNEUTA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. RYZNEUTA is a leukocyte growth factor indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. ( 1 ) Limitations of Use RYZNEUTA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. ( 1 )

2. DOSAGE AND ADMINISTRATION Recommended Dose: 20 mg administered subcutaneously once per chemotherapy cycle. ( 2.1 ) Administer approximately 24 hours after cytotoxic chemotherapy. Do not administer between 14 days before and 24 hours after administration of cytotoxic chemotherapy. ( 2.1 ) 2.1 Recommended Dosage The recommended dosage of RYZNEUTA is a single subcutaneous injection of 20 mg administered once per chemotherapy cycle at least 24 hours after cytotoxic chemotherapy. Do not administer RYZNEUTA within 14 days before and <24 hours after administration of cytotoxic chemotherapy. 2.2 Administration RYZNEUTA is administered subcutaneously via a single-dose prefilled syringe by a healthcare professional. Prior to use‚ remove the carton from the refrigerator (keeping the prefilled syringe inside the carton) for a minimum of 30 minutes to allow the product to reach room temperature. Discard any product left at room temperature for greater than 48 hours. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer RYZNEUTA if discoloration or particulates are observed. Caution: This product contains natural rubber latex which may cause allergic reactions. The needle cap on the prefilled syringe contains natural rubber; people with latex allergies should not administer this product. The RYZNEUTA prefilled syringe does not bear graduation marks and is intended only to deliver the entire contents of the syringe (20 mg/mL) for direct administration to adult patients. Administer injection by pinching the skin and holding. Inject into the abdomen, the back or side of the upper arms, or the thighs. Rotate injection sites. Do not inject into scar tissue or areas that are reddened, inflamed, or swollen. If injecting into the abdomen, avoid a 2-inch diameter circle around the navel. Once the entire dose has been injected, the needle safety device will be triggered, pulling the needle automatically from the skin, and into the barrel; the entire needle will be covered by the needle guard.

6. ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Splenic Rupture [see Warnings and Precautions ( 5.1 )] Acute Respiratory Distress Syndrome [see Warnings and Precautions ( 5.2 )] Serious Allergic Reactions [see Warnings and Precautions ( 5.3 )] Sickle Cell Crisis in Patients with Sickle Cell Disorders [see Warnings and Precautions ( 5.4 )] Glomerulonephritis [see Warnings and Precautions ( 5.5 )] Leukocytosis [see Warnings and Precautions ( 5.6 )] Thrombocytopenia [see Warnings and Precautions ( 5.7 )] Capillary Leak Syndrome [see Warnings and Precautions ( 5.8 )] Potential for Tumor Growth Stimulatory Effects on Malignant Cells [see Warnings and Precautions ( 5.9 )] Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer [see Warnings and Precautions ( 5.10 )] Aortitis [see Warnings and Precautions ( 5.11 )] Most common adverse reactions (≥10%) were nausea, anemia, and thrombocytopenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Acrotech Biopharma Inc at 1-888-292-9617 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The following adverse reaction data are based on two studies [see Clinical Studies ( 14 )]. The first was a randomized, double-blind, placebo-controlled study in patients with metastatic or non-metastatic breast cancer receiving doxorubicin 60 mg/m 2 and docetaxel 75 mg/m 2 every 21 days (Study GC-627-04). A total of 122 female patients were randomized to receive either 20 mg RYZNEUTA (n=83) or placebo (n=39) in chemotherapy cycle 1; all patients received RYZNEUTA in cycles 2-4. The second was a randomized, open-label, active-controlled study in patients with stage I to III invasive breast cancer receiving docetaxel 75 mg/m 2 and cyclophosphamide 600 mg/m 2 (Study GC-627-05). A total of 393 patients were randomized to receive either 20 mg RYZNEUTA (n=197) or pegfilgrastim (n=196) in chemotherapy cycles 1 through 4. In Study GC-627-04, the most common adverse reactions (≥10%) in the RYZNEUTA arm through cycle 1 were nausea, anemia, and thrombocytopenia (see Table 1). Other adverse reactions reported by ≥ 20% of RYZNEUTA-treated Patients with Breast Cancer Receiving Myelosuppressive Chemotherapy in Study GC-627-05 were fatigue and bone pain. Table 1. Adverse Reactions Adverse reactions that occurred in ≥10% of Ryzneuta-treated patients and ≥5% more than placebo-treated patients. in Study GC-627-04 in RYZNEUTA-treated Patients with Breast Cancer Receiving Myelosuppressive Chemotherapy Through Cycle 1 Adverse Reactions Ryzneuta (n=83) Placebo (n=39) Nausea 42 (51) 15 (39) Anemia 12 (15) 4 (10) Thrombocytopenia 10 (12) 1 (3)