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12:00 AM
Apr 30, 2007
 |  BioCentury  |  Product Development

Celsentri: Resisting precaution

The rapid FDA review of Pfizer Inc.'s Celsentri maraviroc only four months after submission of the NDA shows that the agency can move rapidly when it wants to and that it is willing to collaborate with industry and the scientific community to get novel therapies to patients. If FDA agrees with last week's unanimous advisory panel vote in favor of approval it would mark the opening of a new therapeutic class -CCR5 antagonists for HIV - despite unresolved dosing questions about Celsentri and safety issues for other members of the class.

The Celsentri story is exceptional because FDA and the medical community have reacted proactively to safety concerns, rather than apply a precautionary approach. It would be easy to extrapolate adverse events that were uncovered in trials of other CC chemokine receptor 5 antagonists to the entire class, but the advisory committee, and apparently FDA, have decided to resist this temptation.

The Antiviral Drugs Advisory Committee had no concerns about Celsentri's ability to produce clinically relevant suppression of HIV-1 in patients who have run through existing therapies and desperately need a new drug. Indeed, the trials were an object lesson both of how a sponsor can demonstrate efficacy of a novel drug against a crowded background of highly effective therapies and how to enroll the patients most likely to benefit from targeted therapies.

PFE is conducting two 48-week Phase IIb/III trials comparing the safety and efficacy of two doses of Celsentri - 300 mg once or twice daily - plus optimized background therapy versus optimized background therapy alone. All patients were heavily pre-treated, screened to determine that they were infected with CCR5-tropic HIV-1 and did not have detectable CXCR4- or dual-tropic virus.

The application for accelerated approval is based on 24-week data from the ongoing studies. FDA agreed with PFE that both doses of Celsentri met the primary endpoint, a greater mean decrease in HIV-1 RNA from baseline to weeks 24 and 28 than placebo(see "Celsentri Data").

FDA's review also noted that only 29% (172/585) of patients in the maraviroc arms of the trials discontinued treatment by week 24 compared to 51% (106/209) of patients in the control arms (p<0.0001).

"The main...

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