NexoBrid for Eschar Removal in Thermal Burns

On December 28, 2022, the FDA granted approval to anacaulase-bcdb (NexoBrid) for eschar removal in adults with deep partial thickness (DPT) and/or full thickness (FT) thermal burns.¹ Current standard of care for DPT and/or FT burns includes excisional debridement and autografting,² which comes with risks of serious complications. Eschar removal is critical to this step, often requiring a surgical approach. Nonsurgical approach has historically been limited to minimally elective topical agents, requiring significant time for elect. Anacaulase-bcdb is a bromelain-based, proteolytic enzyme concentrate that, when applied, dissolves burn wound eschar in a nonsurgical setting.³

Efficacy

Anacaulase-bcdb has been evaluated in 2 clinical trials. The phase 3 DETECT clinical trial (NCT02148705) compared anacaulase-bcdb with standard of care (SOC) and gel placebo in a 3:3:1 ratio in adult patients with DPT and/or FT burns up to 30% total body surface area (TBSA) in a topical treatment period. Among 169 adult patients, the incidence of greater than 95% eschar removal at the end of the topical treatment period was 93% and 4% in the treatment and gel arms, respectively (treatment diference, 89%; 95% CI, 74%-96%). The incidence of surgical eschar removal in the treatment group was 4% vs 72% among those treated with SOC (treatment diference, –68%; 95% CI, –78% to –56%). Median time to eschar removal was 1 vs 4 days in the treatment arm vs SOC group; median time for wound closure was 31 and 36 days, respectively.⁴

The second study was a multicenter, open-label, randomized, 2-arm study (NCT00324311) of patients with DPT and/or FT burns of 5% to 24% TBSA; efcacy was evaluated in DPT burns. A total of 156 patients were randomly assigned to the treatment or SOC groups. Incidence of surgical eschar removal was 22% and 77% in each group, respectively (treatment diference, –55%; 95% CI, –71% to –38%). Median times to greater than 95% wound closure were 33 and 24 days in each group, respectively.²

Safety

Across both clinical trials, only 2 adverse events were reported at greater than 10%. Pruritus was reported in 15% of treatment patients and 13% of SOC patients, whereas pyrexia was reported in 12% and 9% of patients in each group.

Postmarketing safety data remain limited. Safety and efectiveness of anacaulase-bcdb has not been established in chemical or electric burns; burns on the face, perineum, or genitalia; feet burns of those with diabetes or those with occlusive vascular disease; circumferential burns; or burns in patients with signifcant cardiopulmonary disease including inhalation injury. Additionally, anacaulase-bcdb is not recommended in wounds with radioactive and/or hazardous substances.

Dosing and Administration

Anacaulase-bcdb is supplied as 2 components, a lyophilized powder and a gel vehicle to be mixed prior to administration. Vial components come in 2 g (mixed in 20 g of gel) or 5 g (mixed in 50 g of gel). Drug preparation should be done at the patient’s bedside within 15 minutes of anticipated application. Anacaulase-bcdb should completely cover the burn wound area, be covered with a sterile occlusive flm dressing, and be appropriately dressed with a sterile loose, thick, and fufy dressing and secured with a sterile bandage. The dressing should remain on the wound for 4 hours, followed by appropriate removal procedures.

Patients may require a second application of anacaulase-bcdb if the wound area is more than 15% BSA, if there are logistical reasons for a second application (ie, body position), or if the removal of the frst application was not complete. If considering a second application, anacaulase-bcdb may be reapplied 24 hours following the frst application.¹

References

1. NexoBrid. Prescribing information. Vericel Corporation; 2022.Accessed January 9, 2023.https://www.nexobrid-us.com/pdf/nexobrid-full-prescribing-information.pdf 

2. Rosenberg L, Krieger Y, Bogdanov-Berezovski A, Silberstein E, Shoham Y, Singer AJ. A novel rapid and selective enzymatic debridement agent for burn wound management: a multi-center RCT. Burns. 2014;40(3):466-474. doi:10.1016/j.burns.2013.08.013

3. NexoBrid: disruptive therapy for burn care. MediWound. Accessed January 9, 2023.https://www.mediwound.com/products/nexobrid/ 

4. A study to evaluate the efficacy and safety of NexoBridin subjects with thermal burns. ClinicalTrials.gov. Updated February 19, 2019. Accessed January 9, 2023.https://clinicaltrials.gov/ct2/show/NCT02148705