Lack of CMC information puts clinical hold on trial
Ziopharm Oncology, a Boston-based biotechnology company focused on the development of immunotherapies using gene- and cell-based therapies to treat patients with cancer, believes that its point-of-care CAR-T production technology will eliminate the complex, expensive supply chain and facilities needed to manufacture first-generation therapies from Gilead and Novartis. “Instead of shipping cells from hospitals to production plants and back again, all processing will take place within two days at the healthcare center, thereby driving down treatment costs,” reported Nick Paul Taylor of Fierce Biotech.
However, the first trial to use the CD19-specific technology has come to a halt, because the Food & Drug Administration (FDA) has put a clinical hold on Ziopharm’s phase 1 CAR-T trial. While the company is hoping to run the study to assess CAR-T cells manufactured at the point of care, the FDA is insisting on additional chemistry, manufacturing and control (CMC) information before enabling the trial to continue.
According to a company press release, Ziopharm, Precigen, Inc., a wholly-owned subsidiary of Intrexon Corporation (NYSE:XON) and The University of Texas MD Anderson Cancer Center, the IND sponsor, are seeking to conduct a clinical trial to evaluate CAR-T cells manufactured with Sleeping Beauty technology as an investigational treatment for patients with relapsed or refractory, CD19+ leukemias and lymphomas. CAR-T cells very quickly manufactured with the Sleeping Beauty platform for this third-generation trial are designed to co-express CD19-specific chimeric antigen receptor, or CAR, membrane-bound interleukin 15 and a safety switch.
While Ziopharm CEO Laurence Cooper, M.D., Ph.D., said his company understands what it needs to do in in order to deal with the reasons for the clinical hold and intends to answer the FDA “in a timely manner,” Ziopharm has not yet divulged additional details about why the FDA is putting the hold on the program. The company has not yet committed to a target date for getting past the regulatory hurdle.
Cooper said, “We are undertaking cutting-edge science and are on the verge of a paradigm shift based on our approach to very-rapidly manufacture CD19-specific T cells within two days using our non-viral approach to CAR-T therapy based on the Sleeping Beauty platform.”
Ziopharm shares dropped 12 percent in premarket trading after the news about the hold was released. The decline signals the concern about the hold for the upside of a technology that is critical to Ziopharm’s plans. Successful production of a point-of-care CAR-T would lift the embryonuc market by reducing costs and turnaround times, but the FDA has to be convinced that theearly-phase approach to a novel technology will offer a safe, efficacious therapy. The FDA delay—and lack of details about it—adds to those doubts.
Until Ziopharm began this clinical trial, its top priority was to get inducible adenoviral vector Ad-RTS-hIL-12 into a pivotal brain cancer trial, Taylor reported. That priority shifted in May when a difficult CMC issue caused the biotech company to refocus its priorities, halting the phase 3 clinical trial indefinitely in order to enhance its emphasis on point-of-care CAR-T and other early-phase programs.