GPC Shifts Satraplatin Focus From First-Line To Second; Study Cleared In SPA

The German biotech firm GPC will proceed with a Phase III trial of its oral prostate cancer therapy satraplatin as a second-line treatment following FDA's clearance of a special protocol assessment.

In conjunction with its decision to shift focus for the platinum analog from first-line to second-line treatment of hormone-refractory prostate cancer, GPC decided to pursue an SPA "in order to maximize the chances of registrational success."

"We decided to pursue registration for second-line chemotherapy instead…because the path to approval for second-line provides several major advantages," VP-Drug Development Marcel Rozencweig, MD, told investors Sept. 2.

"First, there are already other drugs approved [for] first-line…a nd in the U.S., time to disease progression is not acceptable as a primary endpoint for a registrational trial with a new chemo agent."

Rozencweig also noted that the need for second-line HRPC therapies is increasing due to changing treatment practices. "Over the last few years we have seen a true paradigm shift in the treatment of prostate cancer. Chemotherapy is now being used more aggressively and at earlier stages of the disease," creating a need for second-line therapies.

"What is interesting," he observed, "is that there are many [prostate cancer] trials that are ongoing, but they all compete for the same first-line patients, so in second-line, there are less patients available, but very little competition in terms of clinical trials."

The 50-patient first-line study, presented at the American Society of Clinical Oncology annual meeting June 3, employed overall survival and time to pain/disease progression (TTP) as primary objectives. The study, conducted by the European Organization for Research & Treatment of Cancer (EORTC), compared satraplatin in combination with prednisone (n=27) vs. prednisone alone (n=23), with antiemetics in the background.

While satraplatin was statistically significant for TTP (5.2 months vs. 2.5; p=0.023), it did not reach significance for survival. Overall survival was 14.9 months for satraplatin vs. 11.9 months for prednisone (p=0.579).

"If we had to take survival as an endpoint [for the second-line trial], which, thank heavens, we do not have to do now based on the FDA green light, this would have added another one to two years," CEO Bernd Seizinger, MD/PhD, said. With the current plan, GPC expects to submit an NDA in 2006.

"As far as we are aware, this is the first time since the approval of mitoxantrone [Serono's Novantrone ] that the FDA has actually permitted the use of this surrogate endpoint for a registration study of cancer chemotherapy in prostate cancer, translating into a significantly faster trial compared to survival as the primary endpoint." Novantrone was approved in 1996 as initial chemotherapy, in combination with prednisone, for HRPC.

GPC hopes to enroll in the mid- to high-hundreds of second-line patients. In addition to TTP, the study will evaluate pain control and survival. The trial will use only one 5-HT3 antagonist while the first-line trial used two.

The study is "powered to detect an increase by one-third in the median [TTP], and this has to be contrasted with the doubling or more than doubling that we have seen in the EORTC study," Rozencweig said.

GPC projects satraplatin's annual peak sales to be "greater than $500 mil. with the help of a pharmaceutical partner." The firm is in discussions with potential partners and expects a licensing agreement with "one or more companies prior to receiving marketing approval."

The sales projection assumes other indications for satraplatin, including earlier stages of prostate cancer, and tumor types in which clinical activity has been observed, including small cell lung cancer and ovarian cancer. Combination use with radiotherapy is another possibility and could be especially attractive due to the agent's oral administration route.

A first-line prostate cancer trial in combination with Aventis' Taxotere (docetaxol) is in the planning stages. "We hope to be able, fairly soon, to activate that study," Rozencweig said. ¨¨