Anacaulase-bcdb (Nexobrid)
Number: 1087
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses anacaulase-bcdb (Nexobrid) for commercial medical plans.
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Exclusions
Aetna considers members with any of the following exclusions not eligible for Nexobrid:
- Member with chemical or electrical burns; or
- Member is treating burns to the face, perineum, or genitalia; or
- Member is treating burns on the feet and is also diagnosed with diabetes mellitus or an occlusive vascular disease; or
- Member is treating circumferential burns; or
- Member has significant cardiopulmonary disease, including inhalation injury; or
- Member has wounds contaminated with radioactive and other hazardous substances to avoid unforseable reactions and an increased risk of spreading the noxious substance; or
- Member has burn wounds where medical devices (e.g., implants, pacemakers, shunts) or vital structures (e.g., large vessels) could become exposed during eschar removal; or
- Member has a known hypersensitivity to bromelain, pineapples, papayas, or papain.
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Prescriber Specialties
This medication must be prescribed by or in consultation with a burn specialist or plastic surgeon.
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Criteria for Initial Approval
Aetna considers anacaulase-bcdb (Nexobrid) medically necessary for eschar removal in adult and pediatric members with deep partial thickness and/or full thickness thermal burns when the following criteria are met:
- The body surface area (BSA) being treated per session does not exceed 15% BSA or does not exceed 10% BSA for pediatric members less than 6 years of ageFootnote*; and
- If for an adult member and a second application is clinically indicated, it must be applied 24 hours following the first application (e.g., if first application is on Tuesday, the second application must be on Wednesday) to either the same area previously treated with Nexobrid or to a new areaFootnote 2** and when any of the following criteria are met:
- The wound area is greater than 15% BSA; or
- Multiple wound areas on different body surfaces require additional treatment for logistical reasons such as body position; or
- The first application did not fully remove eschar from the wound area.
Footnote1*Nexobrid can be applied to a burn wound area of up to 15% BSA in one application in pediatric members 6 years of age and older. Nexobrid can be applied to a burn wound area of up to 10% BSA in one application in pediatric members less than 6 years of age.Footnote2**A second application of Nexobrid is not recommended for pediatric members. For adult members, the second application must occur within the next calendar day from the first application for the same treatment course.Note: For both applications, the total treated area with Nexobrid must not exceed 20% for the same treatment course. Remove Nexobrid after 4 hours per application.
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Continuation of Therapy
Aetna considers continuation of anacaulase-bcdb (Nexobrid) therapy medically necessary for all members (including new members) for a new treatment course (i.e., a new wound or new wound area different from the initial or prior treatment course) who meet all initial medical necessity selection requirements in the criteria for initial approval section.
Dosage and Administration
Anacaulase-bcdb is supplied as Nexobrid topical gel 8.8% for topical use only.
Nexobrid lyophilized powder and gel vehicle must be mixed prior to administration.
- Use 2 g of Nexobrid lyophilized powder mixed with 20 g gel for treatment of up to 180 cm2 of treated burn area; or 5 g of Nexobrid lyophilized powder mixed with 50 g gel for treatment of up to 450 cm2 of treated burn area.
- Dosage in adult individuals:
- Apply a 3 mm thick layer of Nexobrid in one application to an area of up to 15% body surface area (BSA) for four hours.
- A second application may be applied 24 hours later.
- For both applications, the total treated area must not exceed 20% BSA.
- Dosage in pediatric individuals 6 years of age and older:
- Apply a 3 mm thick layer of Nexobrid in one application of 4 hours to an area of up to 15% BSA.
- A second application of Nexobrid is not recommended.
- Dosage in pediatric individuals less than 6 years of age:
- Apply a 3 mm thick layer of Nexobrid in one application of 4 hours to an area of up to 10% BSA.
- A second application of Nexobrid is not recommended.
- Prepare Nexobrid at the individual's bedside within in 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.
- Nexobrid is only to be administered by a healthcare provider.
- Precautions should be taken to avoid exposure to Nexobrid during preparation and handling (e.g., use gloves, surgical masks, other protective coverings, as needed).
- Refer to full prescribing information for additional details on preparation, administration, and removal of Nexobrid.
Source: Vericel, 2024
Not Medically Necessary
Aetna considers treatments with anacaulase-bcdb (Nexobrid) performed less than 24 hours after the first application for the same treatment course is not medically necessary.
Aetna considers any treatment with anacaulase-bcdb (Nexobrid) that is more than one calendar day after the first application for the same treatment course is not medically necessary.
Aetna considers a second application for the same treatment course of anacaulase-bcdb (Nexobrid) for pediatric members is not considered medically necessary.
Background
U.S. Food and Drug Administration (FDA)-Approved Indications
- Nexobrid contains proteolytic enzymes and is indicated for eschar removal in adults and pediatric patients 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;
- Treatment of burn wounds where medical devices (e.g., implants, pacemakers, shunts) or vital structures (e.g., large vessels) could become exposed during eschar removal.
Anacaulase-bcdb is available as Nexobrid (Vericel Corporation), a mixture of proteolytic enzymes extracted from the stems of pineapple plants (Ananas comosus [L.] Merr.) that has been filtered and lyophilized. Nexobrid is made of mainly (80% to 95% w/w) of the proteins: stem bromelain, ananain, jacalin-like lectin, bromelain inhibitors, and phytocystatin inhibitor; and saccharides, as both free monosaccharides and the N-linked glycan of stem bromelain, and small molecule metabolites. The enzyme mixture in Nexobrid dissolves burn wound eschar. The specific components causing this effect have been unidentified (Vericel, 2024).
According to the prescribing information, Nexobrid carries the following contraindications, warnings and precautions, and adverse reactions:
Contraindications
- Known hypersensitivity to Nexobrid, bromelain, pineapples, or to any of the other components.
- Known hypersensitivity to papayas or papain because of the risk of cross-sensitivity.
Warnings and precautions
- Hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, have been reported with postmarketing use of Nexobrid. If a hypersensitivity reaction occurs, remove Nexobrid (if applicable) and initiate appropriate therapy.
- 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.
Adverse reactions
- The most common adverse reactions (>10%) were pruritus and pyrexia.
On December 28, 2022, the U.S. Food and Drug Administration (FDA) approved anacaulase-bcdb (Nexobrid) for eschar removal in adults and pediatric patients with deep partial thickness and/or full thickness thermal burns. The FDA approval was based on supporting data from two clinical trials of 357 patients with deep partial thickness (DPT) and/or full thickness (FT) thermal burns. The investigators conducted the trials in 15 countries including the United States, Romania, Italy, Georgia, Czech Republic, Belgium, Germany, France, Slovakia, Poland, United Kingdom, Austrailia, India, and Israel. Of the 357 enrolled patients, 331 patients were evaluated for efficacy (Intent-to-Treat polulation) (FDA, 2024).
In study 1 (DETECT), a randomized, controlled, assessor-blinded, three-arm trial, investigators compared Nexobrid, standard of care (SOC), and gel vehicle treatment in subjects with DPT and/or FT thermal burns of 3 to 30% body surface area (BSA). SOC included both surgical and non-surgical methods for eschar removal based on the investigators' preference. The health care provider applied Nexobrid or gel vehicle to the treatment area one or two times or used either surgical or non-surgical SOC methods for eschar removal. Any eschar that remained following the topical treatment (i.e., patients in either the Nexobrid of gel vehicle arms) period were treated with SOC. A separate assessor, not involved with treatment, was used to determine the amount of eschar following the topical treatment period (FDA, 2024; Vericel 2024).
In study 1, a total of 175 patients were randomized in a 3:3:1 ratio (Nexobrid (N = 75): SOC (N = 75): gel vehicle (N= 25)) and 169 subjects were treated. Patients had one or more target wounds (TWs) to be treated for eschar removal. The mean percentage BSA of all TWs per patient was 6.1% and the majority of patients (82%) had one to two TWs. Efficacy was assessed by comparing Nexobrid to gel vehicle for the incidence of ≥ 95% eschar removal at the end of the topical treatment period and as the incidence of surgical methods for eschar removal (tangential, minor, avulsion, Versajet and/or dermabrasion excision) for Nexobrid and SOC groups at the time of eschar removal (FDA, 2024; Vericel, 2024).
The incidence of ≥ 95% eschar removal at the end of the topical treatment period was 93% (70/75) for the Nexobrid group and 4% (1/25) for the gel vehicle group (treatment difference; 95% Confidence Interval [CI], 89% [74%, 96%]). The incidence of surgical eschar removal (tangential, minor, avulsion, Versajet and/or dermabrasion excision) and time to ≥ 95% eschar removal was 4% (3/75) for the Nexobrid group and 72% (54/75) for the SOC group (treatment difference; 95% CI, -68% [-78%, -56%]). The median time to eschar removal was 1 day on the Nexobrid arm and 3.8 days on the SOC arm. The estimated median time to ≥ 95% wound closure for all TWs on a subject was 31 days for the Nexobrid arm and 36 days for the SOC treatment arm. Patients were not evaluated often enough after achieving ≥ 95% wound closure to adequately assess time to 100% wound closure (FDA, 2024; Vericel, 2024).
In study 2, a multicenter, open-label, randomized, two-arm trial, investigators compared Nexobrid to SOC treatment in patients with DPT and/or FT thermal burns of 5 to 24% BSA. SOC included both surgical and non-surgical methods for eschar removal based on the investigators' preference. The health care provider applied Nexobrid or gel vehicle to the treatment area one or two times or used either surgical or non-surgical SOC methods for eschar removal. The trial enrolled 182 patients and first patient each site (26 patietns) was not randomized and was treated with Nexobrid. The remaining 156 patients were randomized to Nexobrid or SOC. Efficacy was assessed as the incidence of use of surgical methods for eschar revomal for Nexobrid and SOC groups on DPT burns only (97 patients) (FDA, 2024; Vericel, 2024).
The incidence of surgical eschar removal (tangential, minor, avulsion, Versajet and/or dermabrasion excision) of deep partial thickness wounds in patients with thermal burns is as follows: 1. incidence of excision for eschar removal (per wound) was 15% (16/106 wounds; N=106 wounds in 49 patients) for the Nexobrid group and 63% (55/88 wounds; N=88 wounds in 48 subjects) for the SOC group (treatment difference; 95% CI, -47% [-59%, -34%]), and 2. incidence of excision for eschar removal (per patient) was 22% (11/49 patients; N=106 wounds in 49 patients) for the Nexobrid group and 77% (37/48 patients) for the SOC group (treatment difference ; 95% CI, -55% [-71%, -38%]. In randomized patients, the estimated median time to ≥ 95% wound closure was 33 days for the Nexobrid arm and 24 days for the SOC treatment arm. Patients were not evaluated often enough after achieving ≥ 95% wound closure to adequately assess time to 100% wound closure (FDA, 2024; Vericel, 2024).
On August 15, 2024, the U.S. Food and Drug Administration (FDA), expanded the previous FDA indication approval to include eschar removal in pediatric burn patients wiht deep partial thickness and/or full thickness thermal burns.
The expanded FDA approval was based on supporting data from study 3 (CIDS study), an open label, randomized, controlled, two arm trial, in which investigators compared Nexobrid and standard of care (SOC) treatment in patients 7 months to 18 years of age with DPT and/or FT of ≥1 to 30% BSA. SOC included both surgical and non-surgical methods for eschar removal based on the investigators' preference. Patients in the Nexobrid arm who had eschar remaining after the topical treatment were treated with SOC. Nexobrid was compared with SOC for the time to eschar removal and for the incidence of surgical eschar removal (tangential, minor, avulsion, Versajet and/or dermabrasion excision) (Vericel, 2024).
In the CIDS study, a total of 145 subjects were randomized in a 1:1 ratio (Nexobrid: SOC) and 139 patients were treated. Patients had one or more target wounds (TWs) to be treated for eschar removal. The mean percentage BSA of all TWs per patient was 5.6% and the majority of patients in both treatment groups had 1 TW (71.0% for Nexobrid and 80.0% for SOC) (Vericel, 2024).
The estimated median time to ≥ 95% eschar removal was 0.99 days (95% Confidence Interval [CI]; 0.88, 1.04) for the Nexobrid group compared to 5.99 days (95% CI; 2.71, 9.84) fof the SOC group. The incidence of surgical eschar removal (tangential, minor, avulsion, Versajet and/or dermabrasion excision) was 8% (6/72) for the Nexobrid group (N=72) and 64% (47/73) for the SOC group (N=73), (treatment difference, 95% CI, -56% [-68%, -42%]). The estimated median time to ≥95% wound closure for all target wounds on a subject was 32 days for the Nexobrid group and 34 days for the SOC group. The estimated median time to reach 100% wound closure on a target wound level was 44 days for the Nexobrid group and 43 days for the SOC group (Vericel, 2024).
References
The above policy is based on the following references:
- U.S. Food and Drug Administration (FDA). Drug trials snapshot: Nexobrid. Drugs. Silver Spring, MD: FDA; January 23, 2024.
- Vericel Corporation. Nexobrid (anacaulase-bcdb) for topical gel. Prescribing Information. Cambridge, MA: Vericel; revised August 2024.
