The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to MediWound Ltd regarding the Biologics License Application (BLA) for NexoBrid® (concentrate of proteolytic enzymes enriched in bromelain) for eschar removal (debridement) in adults with deep partial thickness and/or full thickness thermal burns.
NexoBrid is a topically administered, bromelain-based biological product containing a sterile mixture of proteolytic enzymes. The product selectively removes burn eschar within 4 hours without harming surrounding viable tissue.
The BLA is supported by data from the phase 3 DETECT trial (ClinicalTrials.gov Identifier: NCT02148705), which compared NexoBrid to gel vehicle placebo or standard of care (SOC) in adult patients with deep partial and full thickness thermal burns up to 30% of total body surface area (N=175).
Results showed that patients treated with NexoBrid demonstrated a significantly higher incidence of complete eschar removal compared with those treated with placebo (93.3% vs 4%; P <.00011). The trial also met its secondary endpoints. Compared with SOC, NexoBrid was associated with shorter time to complete eschar removal (1 day vs 3.8 days; P <.0001), a lower incidence of surgical eschar removal (4% vs 72%; P <.0001) and lower blood loss during the eschar removal procedure (14.2mL vs 814.5mL; P <.0001). Patients treated with NexoBrid also had a noninferior time to complete wound closure compared with those treated with SOC (P =.00035).
In the CRL, the FDA noted that the BLA could not be approved in its present form due to issues related to chemistry, manufacturing and controls (CMC). In response to the letter, the Company has submitted several CMC amendments and information requests to the FDA, which have not been reviewed for this action. The FDA is also requiring an inspection of manufacturing facilities in Israel and Taiwan before the application can be approved; however, due to COVID-related travel restrictions, the Agency could not conduct the required inspections.
Additionally, “the CRL cited observations identified during good clinical practice (CGP) inspections related to the US phase 3 study (DETECT), and requested the company to provide its perspective on the potential impact, if any, of these observations on the efficacy findings in the study.” While no safety issues were raised in the CRL, the FDA is requesting the Company provide a safety update in its BLA resubmission.
“While we are disappointed that the FDA has issued a CRL for NexoBrid, we remain confident in the strength of our clinical data and in the depth of our development program,” said Sharon Malka, CEO of MediWound. “We remain committed to working collaboratively with the Agency, as well as BARDA, to identify the most expeditious pathway toward a potential approval for this important therapy.”
NexoBrid is currently approved in the European Union and other international markets.
- MediWound receives Complete Response Letter from US FDA for NexoBrid Biologics License Application. [press release]. Yavne, Israel: MediWound Ltd.; June 29, 2021.
- MediWound announces positive top-line results from its pivotal phase 3 study (DETECT) in NexoBrid for eschar removal of severe thermal burns. [press release]. Yavne, Israel: MediWound Ltd.; January 22, 2019.