WASHINGTON - A month after the FDA placed a hold on gene therapy trials involving retroviral vectors to deliver genes to hematopoietic stem cells, the Recombinant DNA Advisory Committee said there's not enough evidence of adverse events attributed to the use of such vectors to warrant halting other human gene transfer studies, including those for non-X-linked severe combined immunodeficiency.
The committee, known as RAC, also said retroviral gene transfer studies for X-linked severe combined immunodeficiency (SCID) should be limited to patients who have failed "identical or haploidentical stem cell transplantation or for whom no suitable stem cell donor can be identified."
Recommendations and findings issued by RAC are forwarded to Elias Zerhouni, director of the National Institutes of Health, said Stephen Rose, deputy director for the Recombinant DNA program in the Office of Biotechnology Activities and executive secretary of RAC. The NIH and RAC make recommendations while the FDA has regulatory authority to stop trials.
As a precautionary measure, the FDA in January placed a clinical hold (stops enrollment of new patients) on all active gene therapy trials using retroviral vectors to insert genes into blood stem cells after a second child treated in a French gene therapy trial developed a leukemia-like condition. The first such event surfaced in a 3-year-old boy who also had been successfully treated for X-linked SCID ("bubble boy syndrome") last August. (See BioWorld Today, Jan. 16, 2003.)
After the first case occurred in August 2002, the FDA identified the three U.S. gene therapy studies that most closely resembled the French trial and stopped enrollment, a statement from the agency said.
At the time, the FDA said it had found no evidence of leukemia caused by gene therapy in U.S. studies involving retroviral vectors.
Nevertheless, RAC took up the issue and the FDA's Biological Response Modifiers Advisory Committee is expected to review it Feb. 28.
RAC had planned a further discussion in early March, but Rose said the panel has decided against that. "What we need to do is step back and get an understanding of exactly what questions need to be answered - some of which might be what animal models would be useful, long-term banking of samples and long-term follow-up," he told BioWorld Today, adding that RAC would have a more clear direction following the Biological Response Modifiers meeting.
FDA officials could not be reached for comment.
Based on its discussion and review of the French case, RAC said the gene transfer was a cause of both leukemia cases, and the event constitutes a "serious inherent risk in this study."
The committee also determined that a majority of the children in the X-linked SCID study experienced major clinical improvement since the trial began about three years ago.
And of the nine children in the study who had successful engraftment of their gamma-c transduced cells, two developed leukemia about three years after treatment, but the overall frequency of the adverse event could not be determined with current information, RAC said.
A prepared statement released by the FDA said in early results of the French study, nine of the 11 participating children had promising results and could leave the hospital and lead relatively normal lives.