SILVER SPRING, MdWith some uncommonly strong and negative comments to Food and Drug Administration staff, the Oncologic Drugs Advisory Committee (ODAC) refused to recommend approval of Roferon-A (interferon alfa-2a recombinant, Hoffmann-La Roche) for use as an adjuvant treatment of surgically resected malignant melanoma without clinical evidence of nodal disease.
The advisory panel acted after listening to analyses of two European studies of stage II malignant melanoma patients (no nodal involvement) presented by Hoffmann-La Roche in support of its application for a new indication for Roferon-A. The drug is currently approved in the United States for the treatment of chronic myelocytic leukemia, hairy cell leukemia, AIDS-related Kaposis sarcoma, and hepatitis C.
The pivotal study involved a French trial in which 246 patients were randomized to receive the drug following surgery and 253 were randomized to observation only after their operations. The primary endpoint was disease-free interval, and at the end of 3 years of follow-up, the French team reported a total of 135 relapses55 in the Roferon-A group and 80 in the observation group.
An Austrian study of 311 patients was offered as supportive evidence. FDA reviewers, however, did not include the Austrian study in their analysis because the company pro-vided full data from the study only about a week before the ODAC meeting, which was insufficient time for a thorough review.
In its analysis of the pivotal study, the FDA review team said that the improvement in disease-free interval noted at 3 years was not significant after adjustment for the thickness of the melanoma lesions or after a review of the trials 6-year follow-up data.
Several ODAC members criticized FDA staff for bringing the Roferon-A application to the committee. Candidly, I think the overall data are highly questionable, said David H. Johnson, MD, director, Division of Medical Oncology, Vanderbilt University Medical School. These are not the quality of data we see coming from this agency that generate approval by this body.
Added Derek Raghavan, MD, PhD, head of Medical Oncology, University of Southern California, As a taxpayer, I really have to say that I dont think youve done as well as you usually do. I shouldnt have to remind you, garbage in, garbage out. I just feel very disappointed that we have to go through this exercise.
Jay P. Siegel, MD, the senior FDA official present at the meeting, said the problem lay in the inability of the agency to obtain additional data it expected from the company in a timely manner after the meeting was scheduled. As you heard, it took us longer than anticipated, he said. The data arrived within the last week or two, and in a preliminary analysis, it did not look like we expected.
ODAC voted 7 to 0 against recommending approval of Roferon-A for this indication, with two abstentions.
In a statement issued after the meeting, Hoffmann-La Roche said, While we appreciate the opportunity FDA provided Roche in reviewing this current filing for the use of Roferon-A to fight stage II malignant melanoma, we are disappointed by the result of the review by the FDAs Oncologic Drugs Advisory Committee.
The statement continued, Because of our desire to meet the growing public need for additional therapies to fight this highly lethal skin cancer, we submitted the application based upon a single pivotal trial. We have based submissions upon, and received approvals for, Roferon-A malignant melanoma treatment in other countries using this same data. We are continuing to invest in Roferon-A research and have a number of additional trials underway.