Washington Editor

Poniard Pharmaceuticals Inc. has laid the groundwork for a pivotal study of picoplatin in the second-line treatment of small-cell lung cancer through a special protocol assessment agreement with the FDA.

Of note, the specialty pharmaceutical company will conduct only a single Phase III trial, testing overall survival as the primary endpoint. The international, multicenter trial, labeled SPEAR (Study of Picoplatin Efficacy After Relapse), will begin in the first half of this year.

The SPA essentially means the study is adequately designed for an eventual marketing application, pending positive data. "In a way, we're creating a novel use for a platinum product by giving it when another platinum fails," said Poniard Chairman, President and CEO Jerry McMahon. He noted that although most small-cell lung cancer patients respond to initial combination therapy that includes platinum treatment, the majority soon relapse. Their overall survival within two years of diagnosis is less than 10 percent.

The new-generation platinum therapy is designed to prevent or overcome platinum resistance associated with chemotherapy in solid tumors, McMahon told BioWorld Today, with an improved safety profile. The FDA has designated it an orphan drug in the indication, which accounts for about one in five lung cancer diagnoses.

"In a way, we're targeting this very poor prognosis population where you can't use a platinum like you did initially," McMahon said, "and for which there really are very few products that you can use that provide clinical benefit and provide quality of life for people with a terminal illness."

South San Francisco-based Poniard expects to enroll about 400 patients who will be randomized in a 2:1 ratio to compare intravenous picoplatin plus best supportive care to best supportive care alone. The study, which should take about 20 months to complete enrollment and follow-up, will include patients who are refractory to treatment with first-line platinum chemotherapy such as cisplatin or carboplatin or who have progressed within six months of completing those treatments.

Patients will be dosed every three weeks with a picoplatin dose of 150 mg/m2. In addition to the primary endpoint of overall survival, secondary measures include overall response rates, progression-free survival and disease control. The company expects to file a new drug application for the indication in 2009.

"As oncology development goes," McMahon said, "this is probably as straightforward of a plan that you could ever imagine. You're going against basically a non-chemotherapy arm, and you're powering it to show a survival difference. There's not a lot of dispute about the data that would be generated from this trial."

The Phase III study's design is based on positive Phase II findings collected to date. Interim data from that ongoing trial, reported in November, showed a median overall survival of 26.7 weeks in the 72 evaluable patients treated with picoplatin, a clear improvement over the National Comprehensive Cancer Network's 16- to 20-week average achieved by patients who receive second-line chemotherapy. A recent study by London-based GlaxoSmithKline plc demonstrated even lower survival numbers, about 13 to 14 weeks.

"In theory, we could approach a 50 percent increase in patient survival if the data we've seen and the published data that Glaxo has observed are recapitulated in our Phase III," McMahon said. "It's a very tough disease, but we learned in our own Phase II how to do a second-line trial in small-cell lung cancer."

That open-label, multicenter Phase II trial also is assessing overall response rates, progression-free survival, improvement in disease-related symptoms and disease control, and at the time of the interim analysis, there had been 22 deaths from disease progression among the 77 picoplatin-treated patients.

Although there were not sufficient data for the last five patients to include them in the interim analysis, findings for all patients will be included in the final analysis. Those final results are expected in June, McMahon said, and will be submitted for presentation at upcoming scientific conferences.

Picoplatin, Poniard's lead drug, was brought in two and a half years ago when the company was still called NeoRx Corp. Exclusive North American and European rights to the compound were in-licensed from Vancouver, British Columbia-based AnorMed Inc., which has since been acquired by Cambridge, Mass.-based Genzyme Corp. (See BioWorld Today, April 6, 2004.)

McMahon said first-line therapy is the ultimate goal for picoplatin to prevent the occurrence of resistant and refractory tumor cells, "what the molecule originally was designed for." Additional clinical trials are testing picoplatin in a combination regimen for colorectal and hormone-refractory prostate cancers. Data from those studies should be released this summer.

On Wednesday, Poniard's stock (NASDAQ:PARD) tacked on 17 cents to close at $5.17. SCRIPT>//