A brain cancer patient died from bleeding in the skull soon after being injected with a Ziopharm Oncology (ZIOP gene therapy directly into the brain tumor.
The Ziopharm patient, diagnosed with a recurrent brain tumor, was treated with the company's experimental gene therapy, known as Ad-RTS-hIL-12. The gene therapy, which is supposed to stimulate a tumor-killing immune response, is injected directly into the patient's tumor. Fifteen days after the Ziopharm gene therapy injection, the patient died from an intracranial hemorrhage.
Ziopharm CEO Laurence Cooper first disclosed the patient death -- which occurred as part of an ongoing clinical trial -- during a presentation at a closed-door scientific workshop in Washington, D.C., on Thursday. Cooper's presentation slides, which included a single bullet point about the patient death, were attached to an 8-K filed Thursday night with the Securities and Exchange Commission.
Ziopharm spokesman David Pitts confirmed the never-before-disclosed death but says the company does not believe the injection of Ad-RTS-hIL-12 into the patient's skull was responsible for the fatal bleeding episode.
However, Pitts concedes that more information about the patient and his fatal skull bleed is still being collected. The FDA has not yet been told about the death.
"This event has just been reported to us and we are following protocol in collecting and analyzing information in order to properly report it to the FDA," said Pitts.
The death of a second patient enrolled in the Ziopharm gene therapy study was also disclosed for the first time Thursday. That patient died 3.9 months following treatment for an undisclosed reason, but unrelated to Ad-RTS-hIL-12, the company says.
The circumstances surrounding the Ziopharm patient deaths come amid heightened scrutiny of experimental anti-cancer therapies. Last week, two blood cancer patients died from treatment with an unapproved CAR-T cellular therapy from Juno Therapeutics.
Ziopharm was trying to raise as much as $50 million in a stock offering this week, but the deal was abandoned Thursday night, according to an email sent by bankers from the investment bank Jefferies & Co. to a prospective investor in the deal. That investor forwarded the Jefferies email to TheStreet.
Concerns about the patient death and the way Ziopharm disclosed it scuttled the stock sale, a second investor source told TheStreet.
"We don't comment on any of the company's confidential activities," said Ziopharm spokesman Pitts.
The Ad-RTS-hIL-12 gene therapy uses a virus encoded with DNA to express interleukin-12 (IL-12), a powerful protein known to stimulate T cells in the immune system to kill cancer cells. The virus is injected directly into a patient's tumor.
Once there, the gene and the production of IL-12 are controlled using an oral drug, veledimex. By raising or lowering the veledimex dose swallowed by patients, Ziopharm says it can control the production of IL-12 to optimize the killing of cancer cells in both injected and non-injected tumors, while also limiting the dangerous side effects (sometimes fatal) caused when IL-12 is administered systemically.
Ziopharm first tried Ad-RTS-hIL-12 in patients with skin cancer, but subpar response rates and competition from other, more effective, cancer immunotherapies led the company to back off that indication. In a study of 12 breast cancer patients treated with Ad-RTS-hIL-12 and veledimex, a single patient had a partial response, according to data presented at a November 2015 cancer immunotherapy meeting.
The FDA is likely to look closely at the information collected by Ziopharm about the patient death in the brain cancer study because the fatal bleed occurred in the same location as the gene therapy injection. The timing of the bleeding death -- 15 days post treatment -- could also be linked to the gene therapy flooding the brain with the IL-12 protein.
For now, Ziopharm says the brain cancer study remains open.Ziopharm shares closed Thursday at $5.67.