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.