BRIEF SUMMARY

EFBEMALENOGRASTIN -(Nov 2023)

Indn-   to treat neutropenia

Comp-   Injection: 20 mg/mL solution in a single-dose prefilled syringe.                            Recommended Dose: 20 mg administered subcutaneously once per chemotherapy cycle. Administer approximately 24 hours after cytotoxic chemotherapy. Do not administer between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

ADR-    Most common adverse reactions (=10%) were nausea, anemia, and thrombocytopenia. 

CI-   Patients with a history of serious allergic reactions to granulocyte stimulating factors such as efbemalenograstim alfa-vuxw, pegfilgrastim, or filgrastim products. 

WARNINGS AND PRECAUTIONS-

 These highlights do not include all the information needed to use  safely and effectively. See full prescribing information for  RYZNEUTA® (efbemalenograstim alfa-vuxw) injection, for subcutaneous use

Pat Inform-

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U.S.  APPROVED DRUGS DURING 2023                                        

Serial No 50

Name-          RYZNEUTA

Active ingedient-       Efbemalenograstin                  

Indication              to treat neutropenia

Date  of approval       11/16/2023 

HIGHLIGHTS OF PRESCRIBING INFORMATION-

WARNINGS AND PRECAUTIONS-

 These highlights do not include all the information needed to use                              RYZNEUTA® safely and effectively.

See full prescribing information for RYZNEUTA. RYZNEUTA® (efbemalenograstim alfa-vuxw) injection, for subcutaneous use

Initial U.S. Approval: yyyy

INDICATIONS AND USAGE-

 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.

 Limitations of Use RYZNEUTA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

ADVERSE REACTIONS-

 Most common adverse reactions (=10%) were nausea, anemia, and thrombocytopenia. 

CONTRAINDICATIONS-

 Patients with a history of serious allergic reactions to granulocyte stimulating factors such as efbemalenograstim alfa-vuxw, pegfilgrastim, or filgrastim products. 

WARNINGS AND PRECAUTIONS-

 These highlights do not include all the information needed to use RYZNEUTA® safely and effectively. See full prescribing information for RYZNEUTA. RYZNEUTA® (efbemalenograstim alfa-vuxw) injection, for subcutaneous use

DOSAGE AND ADMINISTRATION-

 Recommended Dose: 20 mg administered subcutaneously once per chemotherapy cycle. Administer approximately 24 hours after cytotoxic chemotherapy. Do not administer between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

DOSAGE FORMS AND STRENGTHS-

 Injection: 20 mg/mL solution in a single-dose prefilled syringe.

PATIENT COUNSELING INFORMATION-

 Advise the patient to read the FDA-approved patient labeling (Patient Information)

Advise patients of the following risks and potential risks with RYZNEUTA:

 Rupture or enlargement of the spleen may occur. Symptoms include left upper quadrant abdominal pain or left shoulder pain.

Advise patients to report pain in these areas to their healthcare provider immediately

 Dyspnea, with or without fever, progressing to acute respiratory distress syndrome, may occur.

Advise patients to report dyspnea to their healthcare provider immediately

 Serious allergic reactions may occur, which may be signaled by rash, facial edema, wheezing, dyspnea, hypotension, or tachycardia.

Advise patients to seek immediate medical attention if signs or symptoms of hypersensitivity reaction occur

 In patients with sickle cell disease, sickle cell crisis and death have occurred with use of human granulocyte colony-stimulating factors. Discuss potential risks and benefits for patients with sickle cell disease prior to the administration of RYZNEUTA

 Glomerulonephritis may occur. Symptoms include swelling of the face or ankles, dark colored urine or blood in the urine, or a decrease in urine production. Advise patients to report signs or symptoms of glomerulonephritis to their healthcare provider immediately

 Capillary leak syndrome may occur. Symptoms include hypotension and edema. Advise patients to report signs and symptoms of capillary leak syndrome to their healthcare provider immediately

There may be an increased risk of Myelodysplastic Syndrome and/or Acute Myeloid Leukemia in patients with breast and lung cancer who receive RYZNEUTA in conjunction with chemotherapy and/or radiation therapy. Symptoms of MDS and AML may include tiredness, fever, and easy bruising or bleeding.

Advise patients to report to their physician signs and symptoms of MDS/AML

Aortitis may occur. Symptoms may include fever, abdominal pain, malaise, back pain, and increased inflammatory markers.

Advise patients to report signs and symptoms of aortitis to their physician immediately

Manufactured by: EVIVE BIOTECHNOLOGY SINGAPORE PTE. LTD. Singapore, 189720 U.S. License No 2248 © 2023 Evive Biotechnology Singapore PTE. LTD. For more information, go to www.ryzneuta.com or call 1-888-292-961

CLINICAL PHARMACOLOGY-

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.

2. Pharmacodynamics-                                                                                                Over the tested dose range of 30 to 360 µg/kg in healthy adult males, neutrophils generally increased in a dose-dependent manner; however, the effect on neutrophils plateaued at the top two doses of 240 and 360 µg/kg.

3. Pharmacokinetics-                                                                                                    The pharmacokinetics of efbemalenograstim alfa-vuxw was studied in female patients with breast cancer and healthy male subjects.

Absorption-                                                                                                                     The median tmax of efbemalenograstim alfa-vuxw administered as 80 to 320 µg/kg in female patients with breast cancer receiving EC chemotherapy ranged from 24 hours to 48 hours in Cycle 1 and 9 to 30 hours in Cycle 3.

Distribution-                                                                                                                      The geometric mean (CV%) apparent volume of distribution of efbemalenograstim alfa-vuxw was 18.8 L (257%) in Cycle 1 and 40.7 L (387%) in Cycle 3 in female patients with breast cancer.

Elimination                                                                                                                         The geometric mean (CV%) apparent clearance of efbemalenograstim alfa-vuxw was 0.36 L/h (110%) in Cycle 1 and 0.76 L/h (167%) in Cycle 3.

The geometric mean (CV%) elimination half-life of efbemalenograstim alfa-vuxw was 35.6 h (108%) in Cycle 1 and 36.9 h (120%) in Cycle 3.

Metabolism-                                                                                                        Efbemalenograstim alfa-vuxw is expected to be metabolized into small peptides by catabolic pathways.

Specific Populations-                                                                                                           No clinically significant differences were observed based on age (20 to 83 years) or body weight (40 to 137 kg)

The impact of sex, race/ethnicity, renal impairment, hepatic impairment, and pregnancy on the pharmacokinetics of efbemalenograstim alfa-vuxw are unknown.

Immunogenicity- The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay.

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-

 Although available data with RYZNEUTA use in pregnant women are insufficient to establish whether there is a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, there are available data from published studies in pregnant women exposed to other human G-CSF products.

These studies have not established an association of G-CSF product use during pregnancy with major birth defects, miscarriage, or adverse maternal or fetal outcomes..

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15- 20%, respectively.

.2 Lactation Risk Summary-                                                                                                There are no data on the presence of efbemalenograstim alfa-vuxw or its metabolite in either human or animal milk, the effects on the breastfed child, or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for efbemalenograstim alfa-vuxw and any potential adverse effects on the breastfed child from efbemalenograstim alfa-vuxw or from the underlying maternal condition.

3 Pediatric Use-                                                                                                                 Safety and effectiveness in pediatric patients have not been established.

4. Geriatric Use-                                                                                                               Clinical studies of RYZNEUTA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Other reported clinical experience with RYZNEUTA has not identified differences in responses between the elderly and younger patients.

OVERDOSAGE-                                                                                                            Overdosage of RYZNEUTA may result in leukocytosis and bone pain. In the event of overdose, general supportive measures should be instituted, as necessary. Monitor the patient for adverse reactions

11 DESCRIPTION Efbemalenograstim alfa-vuxw, a leukocyte growth factor, is a 413 amino acid recombinant fusion protein consisting of human G-CSF, a 16 amino-acid linker, and the Fc portion of human IgG2. In solution, efbemalenograstim alfa-vuxw forms covalently-linked dimers (disulfide bonds between Fc moieties), resulting in an immunoglobulin-like structure. The dimer is a water-soluble, glycosylated protein with a molecular weight of approximately 93.4 kilodaltons (kDa), of which 89.5 kDa is attributed to amino acids (protein sequence) and the remainder is from glycosylation. Efbemalenograstim alfavuxw is obtained from genetically-engineered strain of Chinese hamster ovary (CHO) cells grown in a serum-free medium. RYZNEUTA (efb