SANDOZ CLOZARIL (CLOZAPINE) IS "1A" AT FDA: APPROVAL IS EXPECTED

Executive Summary

SANDOZ CLOZARIL (CLOZAPINE) IS "1A" AT FDA: APPROVAL IS EXPECTED as early as late September. Sandoz received an "approvable" letter from FDA for the neuroleptic agent Aug. 4. According to the FDA classification system for NDA applications, a "1A" drug is a new molecular entity with significant therapeutic advantage over existing therapies. The drug is indicated for schizophrenics who do not respond adequately to other therapeutic agents. FDA's Psychopharmacologic Drugs Advisory Committee unanimously recommended the drug for approval at an April 26 meeting. A question remains as to whether Clozaril will also be indicated for schizophrenic patients who cannot tolerate other drug therapies. Sandoz submitted an NDA for Clozaril in April 1983. In Feb. 1984, within a year of the submission, FDA's Psychopharmacologic Drugs Advisory Committee met to respond to early evidence of the drug's potential to cause agranulocytosis. Although the panel did not recommend that the drug be dropped from consideration because of safety concerns, the committee did suggest that Sandoz submit additional data to support its therapeutic advantage in treatment-refractory patients ("The Pink Sheet" May 1, p. 7). At the recent April 27 panel meeting, the company presented new data from a pivotal comparative study in patients who had failed on at least three previous treatments. The 16-center trial randomized 268 patients that were either intolerant or nonresponsive to alternative treatments into two groups: 126 patients receiving clozapine and 142 patients treated with a combination of chlorpromazine and benztropine over a period of six weeks. FDA's review of the data concluded that clozapine was effective in approximately 30% of the patients while the combination was effective in approximately 6%.