FDA Panel Unanimously Recommends Centocor’s Ustekinumab
This article was originally published in The Pink Sheet Daily
Executive Summary
But Dermatologic and Ophthalmic Drugs panel says the proposal for long-term safety follow-up is inadequate.
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FDA's Dermatologic and Ophthalmic Drugs Advisory Committee unanimously recommended Centocor's psoriasis drug ustekinumab for approval, but called for the sponsor to conduct more long-term studies during a June 17 meeting. The committee concluded that the drug demonstrates efficacy. "This drug has the potential to be so powerfully helpful to patients," said temporary voting member Lynn Drake, Massachusetts General Hospital. "We know it can help them; we don't know if it can hurt them ... so I think the answer is to do follow-up studies," Drake said. Centocor's immunosuppressant blocks a shared subunit of IL-12 and IL-23, which may lead to increased malignancy. However, such cases have been observed in animal, not human, studies (1 (Also see "FDA Notes Theoretical Cancer Risk For Centocor’s Ustekinumab" - Pink Sheet, 13 Jun, 2008.)). Temporary voting member Tor Shwayder, Henry Ford Medical Center, cited several cases in the medical literature where IL-12 blockage led to increased carcinogenicity. [Editor's note: This story originally indicated that increased risk of malignancies was identified in preclinical studies of ustekinumab. The risk was in fact seen in animal studies of other agents.] "I don't know if we're opening up Pandora's box by blocking IL-12, and that's really the elephant in the room," Shwayder said. Panelists emphasized the need for more long-term safety data, and addressed the firm's proposed long-term studies, including its ongoing PSOLAR trial, intended to monitor the drug's risk of carcinogenicity, cardiovascular events and serious hypersensitivity. "Ultimately the number of patients enrolled in these trials is not going to be sufficient to answer the questions about malignancies," committee chair Michael Bigby, Beth Israel Deaconess Medical Center, said. "I don't think PSOLAR is the solution to this issue." Some members of the committee agreed that five-year extensions of Centocor's two Phase III studies may provide more conclusive information than PSOLAR, noting the benefits of a mandatory patient registry to track events. The committee also discussed the firm's proposed two dose regimen, calibrated for patient weight. FDA proposed an interim 67.5mg dose as an addition to Centocor's proposed 45mg and 90mg doses. But the committee rejected FDA's proposal due a lack of data and requested more dose-response data in general to assist prescribers. -Carlene Olsen ([email protected]) |