The Cellular, Tissue and Gene Therapies (CTGT) Advisory Committee held an open public meeting March 29-30 in Gaithersburg, Md. The first day of the meeting was comprised of presentations and discussions for the new prostate cancer drug – Sipuleucel-T (Provenge®). The committee heard presentations by the Dendreon Corporation and FDA on the new drug, Sipuleucel-T, indicated for the treatment of men with asymptomatic metastatic hormone refractory prostate cancer. The second day was devoted to a discussion of the Food and Drug Administration’s (FDA) draft guidance, Minimally Manipulated, Unrelated, Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution in Patients with Hematological Malignancies, which was released Jan 17.
The Dendreon Corporation presented evidence from several clinical trials that indicated the effectiveness of the new drug and sought FDA approval to market the product. In addition to the compelling evidence from Dendreon, there was testimony from many patients who had received the treatment and those that would like to have the option to receive the treatment. As with any new drug, there is some uncertainty about potential side effects, but patients and patient advocates stated that they want to have the choice on whether or not take the treatment because currently there are not many options, and this treatment appears to offer improved quality of life. The FDA raised the concern that the clinical trials did not include a fair representation of ethic minorities. This shortcoming was acknowledged by the manufacturer, which stated that it plans to continue to collect data post-marketing to obtain additional minority data.
The advisory committee was asked by the FDA to vote on two issues: 1) if the data submitted established that Sipuleucel-T is reasonably safe for the intended population; and 2) if the data submitted demonstrated substantial evidence of efficacy of Sipuleucel-T in the intended population. While the advisory committee’s vote on the first issue was a unanimous affirmative, the second issue resulted in 13 affirmative and four no votes. The takeaway to the FDA was that the drug should be licensed for the stated intended use for the stated intended population.
The agenda for the second day focused on the draft guidance – Minimally Manipulated, Unrelated, Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution in Patients with Hematological Malignancies. The advisory committee was asked by the FDA to consider four issues: 1) types of data that could be submitted to demonstrate comparability between the previously manufactured hematopoietic stem/progenitor cells – placenta/cord blood (HPC-C) and HPC-C manufactured currently; 2) comment on the clinical indications described in the draft guidance; 3) the recommendations in the draft guidance; and 4) what data would be adequate to demonstrate safety and efficacy for hematopoietic stem/progenitor cells – apheresis (HPC-A) and consider approach to licensure of HPC-A similar to the one proposed for cord blood. Due to the technical content of the draft guidance document, five industry experts augmented the advisory committee membership.
Another point that the FDA stressed was its current thinking of how to demonstrate comparability of previously manufactured HCP-Cs and currently manufactured HPC-Cs. If the manufacturer utilized the same procedure included in its BLA for previously manufactured HPC-Cs and has appropriate documentation, the previously manufactured HPC-Cs can be licensed. However, if the manufacturer utilized a different procedure for the previously manufactured HPC-Cs than was submitted in their BLA, then it must demonstrate comparability to currently manufactured HPC-Cs and provide evidence of conformance to Good Manufacturing Practices. A few of the tests mentioned that could demonstrate comparability are total nucleated cell count, viable CD34+ cell count, colony forming units, clinical outcome, and/or citation to medical literature. It would be up to the manufacturer to determine what data is available and provide that justification to the FDA.
During the open public hearing, representatives from AABB, American Society for Blood and Marrow Transplantation (ASBMT), Foundation for the Accreditation of Cellular Therapy (FACT), International Society for Cellular Therapies (ISCT), National Marrow Donor Program (NMDP) and NETCORD presented comments on the draft guidance document. Common themes emerged, such as: 1) what mechanisms are available to demonstrate comparability of previously manufactured HPC-Cs and currently manufactured HPC-Cs; 2) the potential effect on imported products; 3) what mechanism would be in place for continued use if imported products are not licensed; and 4) agreement that NDC numbers should not be required.
The meeting concluded with a short discussion about the possibility of drafting a similar guidance document for HPC-A.