NIH’s RAC TO DISCUSS GENE THERAPY "COMPASSIONATE USE" MECHANISM

NIH's RAC TO DISCUSS GENE THERAPY "COMPASSIONATE USE" MECHANISM at a special meeting scheduled for Jan. 14 in Bethesda, Md. The Recombinant DNA Advisory Committee (RAC) discussion of a compassionate use policy, announced in the Dec. 30 Federal Register, will be stimulated by the group's formal evaluation of a gene therapy protocol submitted by Ivor Royston, MD, San Diego Regional Cancer Center (SDRCC), that received the first-ever approval for compassionate use by National Institutes of Health Director Bernadine Healy, MD, on Dec. 28. In the letter allowing Royston to initiate the gene therapy protocol, NIH Deputy Director Lance Liotta, PhD, states: "Pending FDA approval for safety, Dr. Healy has approved your compassionate plea request for a single-patient gene therapy. In view of the crucial nature of the RAC review, this one-time decision is non- precedent setting and will not create any rights, interest obligations for you or any other investigators in the future." SDRCC said Dec. 30 that FDA had not yet granted the one-person IND for the gene therapy due to outstanding questions of sterility and viability. However, SDRCC said it believed FDA approval to be imminent and planned to begin treatment on Jan 4. Although RAC did not support the protocol initially when Royston floated the concept at its last meeting on Dec. 3-4, the committee did agree that a compassionate use mechanism should be developed and established by a working group on the subject. The working group, headed by RAC member LeRoy Walters, PhD, Kennedy Institute of Ethics, Georgetown University, will provide the committee with a prototype mechanism for discussion at the Jan. 14 meeting. In a Dec. 2 letter to Nelson Wivel, MD, director of NIH's Office of Recombinant DNA Activities (ORDA), Walters provided insight into his view of a satisfactory compassionate use approach. Walters noted that under a protocol that already has been "reviewed and recommended for approval by the RAC and approved by the NIH Director, it should be possible for minor deviations from the precise terms of the protocol to occur." Following approval of the deviations by ORDA, the RAC chair and two RAC members, the protocol could then be brought to the next public meeting of the committee, Walters suggested. SDRCC's Royston requested RAC's review of the protocol, entitled "Phase I Study of Cytokine Therapy of Cancer, Active Immunotherapy of Glioblastoma with Tumor Cells or Fibroblasts Genetically Modified to Secrete Interleukin-2," in a Dec. 7 letter. Royston sought the compassionate use of the gene therapy protocol on behalf of a San Diego woman dying from a grade 4 glioblastoma brain tumor. When Royston had informally talked about a possible protocol at RAC's December meeting, he initially received a lukewarm response from the committee, which cited the need for additional information before the gene therapy could be approved. However, in the weeks following the RAC meeting, Royston provided additional data to NIH including institutional review board (IRB) review and biosafety information. In addition, NIH also realized that the vector to be used by Royston was approved by RAC at its June 2 meeting. The vector was part of a protocol submitted to the committee by Bernd Gansbacher, MD, Memorial Sloan-Kettering, for use in the treatment of metastatic melanoma and renal cell carcinoma ("The Pink Sheet" June 8, T&G-10). According to NIH, Gansbacher will provide the vector to Royston. Sen. Harkin (D-Iowa), who chairs the Appropriations/HHS Subcommittee in charge of NIH funding, has taken an interest in the woman's case and has suggested a possible legislative fix to allow for the approval of compassionate use gene therapy protocols in terminally ill patients. In an Oct. 8 letter to NIH's Healy, Harkin sought a compassionate use waiver that would have allowed Royston's protocol to be used on the woman, who has Iowa connections. The letter raised the issue of a legislative solution in the 103rd Congress. Harkin, however, is still in favor of NIH approval of all gene therapy protocols, compassionate use or otherwise.