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 cancer.
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.