GAITHERSBURG, Md--Faced with significant differences between FDA
staff and company-associated scientists in the analysis of data
from two clinical studies, the FDA's Oncology Drugs Advisory Committee
(ODAC) declined to vote either way on whether to recommend approval
of Pharmacia & Upjohn's Remisar (bropirimine tablets) for
the treatment of patients with BCG-refractory or BCG-intolerant
urinary bladder carcinoma in situ (CIS).
Dispute Over Complete Responders
The panel instead advised the FDA and the sponsoring company to
see if they could satisfactorily resolve the discrepancies between
their interpretations of the pooled data from the nonran-domized
studies involving a total of 105 patients.
The sponsor claims 25 patients (24%) responded completely; another
30% had no response. FDA evaluators, however, put the number of
complete responders at nine.
Bladder CIS often responds well to intravesical BCG (TICE BCG,
TheraCys). However, about 30% of patients with diffuse CIS are
refractory to this treatment or cannot tolerate it. Urologists
generally consider these people candidates for immediate cystectomy
because they are at high risk of developing invasive and metastatic
The FDA panel members unanimously agreed that a drug producing
a long-lasting, complete remission in a sizable number of CIS
patients would provide a "meaningful clinical benefit."
They disagreed with Pharmacia & Upjohn, however, that the
company had proved that Remisar was that drug.
In its safety evaluation, the sponsor included participants from
a third Remisar bladder CIS trial. No increase in urinary events
occurred, but increases in some cardiovascular episodes were seen
among the 134 patients in the analysis.