GTx announced 11/2/2009 that it has received a Complete Response Letter from the FDA concerning its NDA for TOREMIFENE CITRATE 80 mg (ACAPODENE®). The NDA, filed in late December 2008, sought approval for use of toremifene 80 mg to reduce fractures in men with prostate cancer receiving androgen deprivation therapy (ADT). The NDA was based on a single 2 year double-blind Phase III trial that randomized 1,389 ADT patients in 150 clinical sites. The primary endpoint was new morphometric vertebral fractures. Secondary endpoints included bone mineral density, lipid changes, hot flashes and gynecomastia (hyperlinks are to sources of these Phase III trial endpoint results).
According to GTx, the FDA Letter identified two deficiencies:
“(i) results of a second adequate and well controlled Phase III trial demonstrating the safety and efficacy of toremifene citrate 80mg to reduce fractures in men with prostate cancer on ADT and
(ii) results from an adequate and well-controlled clinical trial demonstrating that toremifene treatment to reduce fractures in men with prostate cancer on ADT does not have a detrimental effect on either time-to-disease progression or overall survival.”
Usually a new indication, such as this, requires 2 adequate and well-controlled Phase III trials. It is not known why GTx filed the NDA with just one trial. The FDA met the PDUFA date of 10 months after the NDA was filed.
GTx had previously reported that “[a]mong men in the intent-to-treat population with a detectable PSA (PSA greater than or equal to 1 ng/ml) at baseline (n=419), significantly fewer men treated with toremifene 80 mg had PSA progression over time compared to men taking placebo (27% versus 37%, respectively; p less than 0.05)”. That is, GTx was using PSA as a surrogate for the underlying prostate cancer. Survival was not reported in the paper. Apparently, FDA did decided not to accept the surrogate marker and now wishes to have actual disease data.
GTx, a publicly traded company, saw a large increase in trading volume and a big drop in its share price.