Ziopharm Oncology has disclosed the deaths of three patients in a Phase I study of its gene therapy candidate Ad-RTS-hIL-12 plus oral veledimex for a form of brain cancer.

The third patient died of an intracranial hemorrhage that occurred sometime following discharge from a treating center for the Phase I study, Ziopharm said today in a statement. The study is designed to assess the combination of Ad-RTS-hIL-12 with orally administered veledimex in patients with recurrent or progressive glioblastoma (GBM) or grade III malignant glioma.

“This is an isolated case, and there have been no reported related instances of brain hemorrhage in any previous cohort or prior studies with Ad-RTS-hIL-12 + veledimex,” Ziopharm stated. “Enrollment remains open in the study, and we will be discussing with our Safety Review Committee the appropriate course of action.”

The statement followed the company’s first disclosure of the deaths yesterday during a presentation by Ziopharm CEO Laurence Cooper, M.D., Ph.D., at an American Society of Hematology workshop—a presentation whose slides were submitted as a regulatory filing to the U.S. Securities and Exchange Commission.

According to Ziopharm, the third patient died 15 days after starting on a 30-mg dose of the gene therapy. The death has yet to be reported to the FDA: “We are collecting and analyzing information in order to properly and timely report it to the FDA.”

The other two patient deaths occurred 6.7 months following a 20-mg dose, and 3.9 months after treatment with a 40-mg dose, the company added, insisting that the deaths were unrelated to the study drug.

“For patients who have experienced multiple recurrences, as these patients have, prognoses are particularly poor,” Ziopharm stated. “For the patients that remain in follow up in this Phase I study, we believe that preliminary overall survival remains encouraging. The Company expects to provide an update once a course of action has been determined.”

On June 27, Ziopharm announced the successful completion of enrollment in the first and second dosing cohorts, as well as the start of enrollment in a third cohort, in the Phase I study. The first cohort of seven patients received 20-mg doses of veledimex, the second cohort of six patients received 40-mg doses of veledimex, and the third cohort will receive 30-mg doses of veledimex to refine the effect of activating the immune response within the tumor, the company said at the time.

The study’s primary objective is to determine safety and tolerability of a single intratumoral Ad-RTS-hIL-12 injection activated upon dosing with oral veledimex. Secondary objectives are to determine the maximum tolerated dose, the immune responses elicited, and assessment of biologic response, Ziopharm has said.

Ad-RTS-hIL-12 is a viral gene therapy candidate for the controlled expression of interleukin 12 (IL-12). Ad-RTS-hIL-12 has been granted Orphan Drug Designation by the FDA for the treatment of patients with malignant glioma.

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