HEPZATO Kit (melphalan/HDS) is resubmitted to FDA for hepatic-dominant metastatic ocular melanoma

The resubmission is in response to a September 12, 2013 Complete Response Letter (CRL) from the FDA. The NDA resubmission contains comprehensive data and information to address all issues identified in the CRL. The FDA is expected to determine whether the resubmission constitutes a complete response and is eligible for review within 30 days. Once accepted for review by the FDA, a new PDUFA action date will be established for the HEPZATO Kit application.

Delcath powered the single arm trial to demonstrate a superior ORR versus checkpoint inhibitors, one of the few mOM treatment categories with a significant amount of peer reviewed publications. The checkpoint inhibitor ORR was calculated based on a meta-analysis covering 16 different publications and 476 patients. Based on those assumptions, a 21.0% ORR was required to demonstrate superiority over the checkpoint inhibitors at a 95% confidence interval. The FOCUS study's intent-to-treat (ITT) population was comprised of a total of 102 mOM subjects. In the ITT population, 91 patients were administered at least one study treatment. Of the 91 patients in the treated population, 51 (56.0%) had no prior therapy for liver metastases and 40 (44.0%) had at least one line of prior therapy. As previously reported, treatment with HEPZATO Kit in the treated population resulted in an ORR of 36.3% [95% CI: 26.44, 47.01] including 7.7% of patients with a complete response (CR). The median duration of response was 14.00 months [95% CI: 8.31, 17.74] and the disease control rate (DCR) was 73.6% [95% CI: 63.35, 82.31].

In addition, the NDA resubmission includes updated estimated median overall survival (OS) of 20.53 months [95% CI: 16.79, 25.26] and updated estimated OS at 1 year of 0.80 [95% CI: 0.70, 0.87]. Delcath will continue to follow patients until May 2023 (24 months after the last patient's last treatment).

In the FOCUS trial safety population (95 patients), 39 patients (41.1%) experienced a treatment-related serious adverse event. The most commonly reported treatment-related serious adverse events were thrombocytopenia, neutropenia and febrile neutropenia which were well-manageable. Five percent of patients experienced treatment-related serious cardiac adverse events; in all cases the events resolved with no ongoing complications. There were no treatment-related deaths in the trial. This is consistent with CHEMOSAT, the HDS device component of HEPZATO Kit, approved in Europe under a CE mark to deliver melphalan to the liver. The safety data submitted in the NDA is consistent with the CHEMOSAT safety data documented in numerous European single-center and multi-center publications.