FDA Holds Up Delcath Systems' NDA Over Safety Concerns

Questions over safety in Delcath Systems' chemotherapy delivery system for melphalan in the treatment of liver tumors caused the FDA to issue a refusal-to-file letter. Delcath Systems' is seeking approval for its proprietary method of chemotherapy delivery under a new drug application (NDA). The company expects to submit a formal meeting request with the FDA to discuss the issues raised in the refusal-to-file letter and to resubmit its NDA by September 30, 2011.

The FDA has the ability to formally file or refuse to file an application within 60 days of the completion of the submission, which occurred on December 22, 2010. Neither the acceptance nor non-acceptance of the NDA filing is a determination of the approvability of the chemosaturation system.

Click on thumbnail to watch a video of Delcath Systems' chemosaturation therapy
 

According to the company, Delcath Systems' has developed a "chemosaturation system" which uses a "percutaneous hepatic perfusion (PHP) procedure to deliver high doses of melphalan hydrochloride directly to the liver for the treatment of ocular and cutaneous metastatic melanoma."

In a late-stage clinical trial reported in April, Delcath revealed that the PHP patients had a statistically significant longer median hepatic progression–free survival (hPFS) of 214 days compared to 70 days in the best alternative care (BAC) arm (P = 0.001). This reflects a 144–day prolongation of hPFS over that of BAC control arm, with less than half the risk of progression and/or death in the PHP group compared to the BAC group (hazard ratio = 0.46).

Melphalan is currently used primarily to treat multiple myeloma. Delcath filed for approval using a 505(b)(2) application, allowing a new use to be considered for the treatment based on already proven safety and efficacy findings.

The company has conducted a phase III trial for ocular and cutaneous metastatic melanoma and a phase II trial for patients with different types of liver cancer.

In a statement Tuesday, Eamonn P. Hobbs, CEO and president of Delcath Systems, said, "The FDA's letter requested information involving manufacturing plant inspection timing, product and sterilization validations and additional safety information that we already planned on filing with our 120 day safety update in April, as well as additional statistical analysis clarification."

The president added: "We believe that we will be able to provide the requested information in an updated application and we expect to resubmit the NDA by the end of the third quarter of this year."