U.S.  APPROVED DRUGS DURING 2022                                        

Serial No 37

Name-        NEXOBRID

Acive  Ingredient -  Anacaulase -bcdb

Pharmacological clssificiation-        To remove Eschar in adults with deep partial                                                                  thickness or full thichness theramal burns                                                                                                                                                                                                                                                                                              Date of Approval-         28/12/2022

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                     NEXOBRID safely and effectively.                                                                                    See full prescribing information for NEXOBRID. NEXOBRID® (anacaulase-bcdb) for topical gel

Initial U.S. Approval: 2022

INDICATIONS AND USAGE                                                                                              - NEXOBRID contains proteolytic enzymes and is indicated for eschar removal in adults with deep partial thickness and/or full thickness thermal burns                                         

 Limitations of Use-                                                                                                        The safety and effectiveness of NEXOBRID have not been established for treatment of:

• Chemical or electrical burns                                                                                              • Burns on the face, perineum, or genitalia                                                                         • Burns on the feet of patients with diabetes mellitus or on the feet of patients with occlusive vascular disease                                                                                                  • Circumferential burns                                                                                                    . • Burns in patients with significant cardiopulmonary disease, including inhalation injury

 NEXOBRID is not recommended for wounds contaminated with radioactive and other hazardous substances to avoid unforeseeable reactions with the product and an increased risk of spreading the noxious substance

ADVERSE REACTIONS-                                                                                                 

  The most common adverse reactions (>10%) were pruritus and pyrexia

CONTRAINDICATIONS-                                                                                                   - • Known hypersensitivity to anacaulase-bcdb, bromelain, pineapples, or to any of the other components                                                                                                             . • Known hypersensitivity to papayas or papain because of the risk of crosssensitivity 

WARNINGS AND PRECAUTIONS-                                                                                 •  Hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, have been reported with postmarketing use of anacaulase..                          If a hypersensitivity reaction occurs, remove NEXOBRID (if applicable) and initiate appropriate therapy

 • Pain: Manage pain as appropriate for an extensive dressing change of burn wounds. At least 15 minutes prior to NEXOBRID-related procedures ensure adequate pain control measures are in place

 • Proteolytic Injury to Non-Target Tissues: NEXOBRID is not recommended for treatment of burn wounds where medical devices or vital structures could become exposed during eschar removal. Protect any open wounds with skin protectant ointments or ointment gauze to prevent possible exposure to NEXOBRID

 • Coagulopathy: Avoid use of NEXOBRID in patients with uncontrolled disorders of coagulation. Use with caution in patients on anticoagulant therapy or other drugs affecting coagulation, and in patients with low platelet counts and increased risk of bleeding from other causes. Monitor patients for possible signs of coagulation abnormalities and signs of bleeding

• See Full Prescribing Information for additional details on preparation, administration, and removal of NEXOBRID

DOSAGE AND ADMINISTRATION-                                                                                   • For topical use only

• NEXOBRID may be applied in up to two applications of 4 hours each                             • A first application may be applied to an area of up to 15% body surface area (BSA)       . • A second application may be applied 24 hours later. The total treated area for both applications must not exceed 20% BSA                                                                              . • Use 1.94 g of anacaulase-bcdb in 2 g powder mixed with 20 g gel per 1% BSA, or 4.85 g of anacaulase-bcdb in 5 g powder mixed with 50 g gel per 2.5% BSA                    • Prepare NEXOBRID at patient’s bedside within 15 minutes of intended application        • Apply NEXOBRID to a clean, moist wound bed free of burned epidermis layer and blisters, and cover with an occlusive film dressing for 4 hours                                         . • See Full Prescribing Information for additional details on preparation, administration, and removal of NEXOBRID

DOSAGE FORMS AND STRENGTHS-                                                                              • For topical gel: 8.8%

 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied-                                                                                                    NEXOBRID (anacaulase-bcdb) for topical gel, 8.8%, is supplied as a package containing two components, a sterile, preservative-free, off-white to light tan lyophilized powder in a glass vial and a sterile, preservative-free, clear and colorless gel vehicle in a glass jar, that are mixed prior to application.

NEXOBRID is available: Reference ID: 5101702                                                                  • One glass vial of 2 g lyophilized powder (containing 1.94 grams of anacaulase-bcdb) and one glass jar of 20 g gel vehicle per carton 

• One glass vial of 5 g lyophilized powder (containing 4.85 grams of anacaulase-bcdb) and one glass jar of 50 g gel vehicle per carton

Storage and Handling-                                                                                               Store and transport NEXOBRID package upright and refrigerated at 2°C to to 8°C (36 °F to 46 °F) in the original carton to protect from light.

DO NOT FREEZE. Do not use if the vial or jar are damaged.

 PATIENT COUNSELING INFORMATION-

Hypersensitivity Reactions-                                                                                    Advise patients of the risk of hypersensitivity reactions, including anaphylaxis

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Dist- by: Vericel Corporation 64 Sidney Street Cambridge, MA 02139                 Man- by: MediWound LTD 42 Hayarkon Street, Yavne 8122745 Israel U.S.    License number XXXX NEXOBRID® is a registered trademark of MediWound LTD

 CLINICAL PHARMACOLOGY-

1. Mechanism of Action-                                                                                              The mixture of enzymes in NEXOBRID dissolves burn wound eschar. The specific components responsible for this effect have not been identified.

2. Pharmacodynamics-                                                                                                     The pharmacodynamics of NEXOBRID are unknown.

Cardiac Electrophysiology-                                                                                            At the approved recommended dose, NEXOBRID did not prolong the QT interval in humans to any clinically relevant extent.

3. Pharmacokinetics -                                                                                              Absorption-                                                                                                            Topically applied NEXOBRID to deep partial and full thickness burn wounds is rapidly absorbed, with median serum Tmax of 4 hours (during the treatment application). Systemic exposure (i.e., AUC) of bromelain, a component of anacaulase-bcbd is correlated with the size of the treated area and NEXOBRID dose, but not the depth of the burn wound.

Elimination-                                                                                                                       A majority of subjects had no quantifiable serum concentrations after 72 hours. The mean ± SD terminal half-life of bromelain, a component of anacaulase-bcbd, is 12 ± 4.4 hours. Cmax and the dose-normalized Cmax values after the first and second application (mean dosing interval of 17 hours) are comparable and only slight accumulation (less than 2-fold difference) is seen in AUC0-4 and AUC0-4 dose-normalized levels after the second application, compared to the first application.

Drug Interaction Studies -                                                                                             Effect of NEXOBRID on Other Drugs Bromelain, a component of anacaulase-bcbd, exhibited CYP2C8 time-dependent inhibition in human hepatocytes and inhibited human microsomal CYP2C9. No clinical studies have been conducted to assess the potential for systemic drug interactions.

 Immunogenicity-                                                                                                      There is insufficient information to characterize the anti-drug antibody response to anacaulasebcdb and the effects of anti-drug antibodies on pharmacokinetics, pharmacodynamics, safety, or effectiveness of NEXOBRID.

 USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-                                                                                    There are no available data on NEXOBRID use in pregnant women to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

The 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 risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% an 15 to 20%, respectively.

2. Lactation Risk Summary-                                                                                     There are no data on the presence of anacaulase-bcdb in either human or animal milk, the effects 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 NEXOBRID and any potential adverse effects on the breastfed infant from NEXOBRID or from the underlying maternal conditio

3. Pediatric Use-                                                                                                           The safety and effectiveness of NEXOBRID in pediatric patients have not been established. 

4. Geriatric Use-                                                                                                              Of the 177 subjects exposed to NEXOBRID for eschar removal in deep partial thickness (DPT) and/or full thickness (FT) thermal burns, 6 (3%) subjects were 65 years or older, and 1 (< 1%) subject was 75 years or older .                                                                  Clinical studies of NEXOBRID did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.