A Medical Device Daily

Delcath Systems (New York) reported that it received a letter from the FDA recommending that the company temporarily suspend enrollment in the Phase III and Phase II trials of the Delcath system, and submit an analysis of adverse events in anticipation of a meeting with the agency to discuss certain gastrointestinal (GI) safety concerns.

The recommendation was issued by the agency following reports of GI events submitted by the company to the FDA that may have been related to the infusion of melphalan.

The company said it plans to submit to the FDA its analysis of these adverse events and their relation to the Delcath system within the next 15 days.

The FDA request comes after Delcath reporting four serious adverse events, including two deaths, in a late-stage trial.

None of the events occurred during the administration of the Delcath procedure but happened afterwards, CEO Richard Taney said in a conference call with analysts about the trial suspension.

Delcath worked with the National Cancer Institute (NCI; Bethesda, Maryland) to amend the protocols, which were approved by the Institutional Review Board at NCI on Sept. 18 and implemented in the trials. There have been no GI toxicities in patients since then, Taney said.

The company said it was unsure if the FDA considered the amended protocols and related data while issuing the letter.

The mid- and late-stage trials used the Delcath system with the drug melphalan to isolate the liver from the general circulatory system to treat the tumors in the liver.

Under the treatment, catheters inserted through the skin are used to deliver drugs to the liver, block the flow of blood from the liver and then remove the drugs. This avoids the complications of a surgery and can be repeated if needed.

The FDA had approved the late-stage trial under a fast track designation and NCI was the lead center in the trial.

About 90 patients have been treated with the Delcath procedure and the current enrollment is 60 patients. The NCI has performed 200 such procedures, Taney said.

The company expects patients currently enrolled in the trials will continue to receive their treatments under the approved protocols.

“We are prepared to meet with the FDA as soon as possible, and will present a thorough analysis of these GI episodes. We will update our investors promptly on resolution of this issue,” Taney said.

Delcath is the developer of percutaneous perfusion technology for organ- or region-specific delivery of therapeutic and chemotherapeutic agents. The Delcath system is currently being tested with the drug melphalan in a Phase III trial of patients with metastatic ocular and cutaneous melanoma in the liver, and a Phase II trial of patients with primary liver cancers and metastatic tumors in the liver from neuroendocrine cancers and adenocarcinomas, as well as patients with melanoma who previously received isolated perfusion.