Leveraging FDA Guidelines
Provenge’s development path provided a basis, in large part, for vaccine developers and regulators struggling to understand appropriate endpoints and biological markers for therapeutic cancer vaccine trials. FDA’s “Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines” was issued in October 2011, a year and five months after Provenge’s approval. “Although the FDA guidelines are new,” Dr. Singh remarked, “they are backed by more than two decades of research and clinical experience, to which members of our scientific leadership meaningfully contributed.”
Dr. Singh offered these tips based on the guidelines: “We believe that conducting a randomized Phase II clinical trial early on is important to understanding clinical outcomes. We also agree that while progression-free survival is an important secondary endpoint, overall survival ought to be the primary indicator of therapeutic efficacy in most immunotherapy trials.
“Our current Phase IIb trial for glioblastoma adheres to these guidelines as we are primarily evaluating overall survival, using disease-free survival as a secondary endpoint.” ImmunoCellular Therapeutics’ lead product candidate, ICT-107, is an autologous dendritic cell-based vaccine.
Carlos F. Santos, Ph.D., svp, product development and regulatory affairs for cancer vaccine developer Biovest told GEN, “We’re encouraged with regard to the current U.S. regulatory environment for targeted oncology therapies with the FDA seemingly becoming increasingly flexible, evidenced by multiple recent approvals, even approving such drugs based on highly positive Phase II data alone.
“Our targeted cancer therapy, BiovaxID, is an autologous active immunotherapy,” Dr. Santos explained. “We are prepared to present what we believe is a compelling case in favor of its approval for the treatment of non-Hodgkin lymphoma.”
Besides Biovest, Immunocellular Therapeutics, and Dendreon, significant players in the cancer vaccine field include Bavarian Nordic and Prima BioMed. Bavarian Nordic’s Prostvac is a nonautologous candidate for advanced prostate cancer in Phase III development. Prima BioMed is investigating CVac, a personalized autologous dendritic cell therapy, as a treatment for ovarian cancer in Phase II.
These companies as well as researchers in earlier stages of R&D for cancer vaccines will fair best if they follow the regulatory guidance provided by the FDA. By lessening the uncertainty that surrounds the development path for this completely novel class of cancer therapies, the agency hopes to incentivize more innovation. On the flip side, though, scientists will have to bear the financial burden associated with increased regulation. Nonetheless, as evidence mounts with regard to biomarkers for clinical response to cancer immunotherapies, developers will have another piece of the puzzle to help make better decisions on clinical development as well as design.