July 15, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Cancer gene therapy technology is taking a hit this week. As the market has beat up on Juno Therapeutics and Kite Pharma over four reported deaths in Juno’s CAR-T gene therapy clinical trials Boston’s Ziopharm Oncology released information that three patients receiving gene therapy for brain tumors have died during the Phase I trial.
Due to three (now four) reported deaths by cerebral edema, a fluid buildup in the brain, the U.S. Food and Drug Administration (FDA) placed a clinical hold on Juno’s JCAR015 clinical trial for relapsed or refractory B cell acute lymphoblastic leukemia on July 8. On July 12, it announced that the FDA had lifted the hold after a change in the protocol. However, today it was announced that there had been an additional death in a related CAR-T trial of JCAR014.
In Ziopharm’s case, a patient diagnosed with a recurrent brain tumor was treated with Ad-RTS-hIL-12, a gene therapy. Ad-RTS-hIL-12 utilizes a virus modified to express interleukin-12 (IL-12), a protein that stimulates T-cells to attack cancer cells. The modified virus is injected directly into a patient’s tumor. Once injected, the gene and the manufacturing of IL-12 are controlled with an oral drug, veledimex.
Ziopharm disclosed this death, which was part of a clinical trial, at a closed-door scientific workshop in Washington, DC yesterday. Results were also included in an 8-K form filed with the U.S. Securities and Exchange Commission (SEC).
At this point, the company has not been able to confirm if the injection of Ad-RTS-hIL-12 into the patient’s brain was the cause of the intracranial hemorrhage. “This event,” said Ziopharma spokesman David Pitts, to The Street, “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.”
At the same time as the reporting of the first death, the company disclosed that two other patients had died who were enrolled in the clinical trial. One patient died 3.9 months after treatment for a reason that was undisclosed, but apparently unrelated to Ad-RTS-hIL-12. The other died about 6.7 months after a 20mg dose, but Ziopharm indicates those deaths are not related to the clinical trial.
“For patients who have experienced multiple recurrences, as these patients have, prognoses are particularly poor,” the company said in a statement. “For the patients that remain in follow up in this Phase I study, we believe that preliminary overall survival remains encouraging.”
Ziopharm picked up its gene therapy technology from Intrexon. It initially investigated Ad-RTS-HIL-12 in skin cancer patients, but didn’t find it to be an effective treatment, particularly in comparison to competitive therapeutic strategies, and has since shifted to breast cancer and brain cancer.
At this time the brain cancer trial is still open, although as mentioned earlier, the FDA has yet to be officially informed of the death. The most recent death occurred 15 days after treatment, but the link has not yet been made between the intracranial hemorrhage and the production of IL-12 protein in the brain.
Ziopharm Oncology is currently trading for $4.88. Shares traded for $14.57 on Nov. 10, 2015, dropped to $4.89 on Jan. 28, 2016, and rose again to $9.59 on Mar. 3.
According to TheStreet, “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 investors in the deal. That investor forwarded the Jefferies email to TheStreet.”
