Washington Editor
Novacea Inc. and its partner Schering-Plough Corp. halted a Phase III trial of an investigational prostate cancer treatment because of a higher rate of deaths in patients receiving the drug, the firms said Monday.
The study, known as ASCENT-2, was comparing Novacea's Asentar (DN-101) plus the chemotherapy agent Taxotere (docetaxel) with Taxotere alone in patients with androgen-independent prostate cancer (AIPC).
Results from a Phase II/III trial showed that patients with AIPC receiving Asentar had an improvement of 49 percent in overall survival vs. patients receiving Taxotere alone.
About 900 patients at multiple centers in various countries, including the U.S., Canada, Germany and Central Europe, were enrolled in the Phase III trial. Just last week, South San Francisco-based Novacea had announced that it planned to increase the enrollment to 1,200 participants. (See BioWorld Today, Oct. 31, 2007.)
On news of the study's termination, shares of Novacea (NASDAQ:NOVC) plunged $4.30 Monday, or 60 percent, to close at $2.89.
The decision to end the Phase III trial, said Novacea CEO John Walker, was based on recommendations by the study's drug safety monitoring board (DSMB), which had observed a "significant imbalance of deaths between the two treatment arms" during a regularly scheduled analysis.
"Given the promising clinical activity observed in our Phase II trial, we are very surprised and disappointed by these findings," Walker said Monday during a conference call. "However, Novacea and Schering-Plough plan to fully analyze the clinical data in an attempt to understand the cause of the higher death rate in the Asentar plus Taxotere treatment group."
The preliminary analysis of Asentar, he said, had "not identified any unexpected safety findings."
While the termination of the Phase III study is "clearly a setback" for Novacea, Walker said, "we still believe that Asentar is a viable cancer treatment." He vowed that the biotech's partnership with Kenilworth, N.J.-based Schering-Plough would continue.
"We will work together to evaluate the results and to determine the next steps," Walker said. "The safety of the patients in our trials is our top concern, and we believe we have taken all of the immediate and appropriate steps in following the DSMB's recommendations. We have informed all relevant constituents, most importantly, the clinical trial sites treating patients and the regulatory authorities, and have suspended enrollment in other ongoing or planned trials until we have had a chance to assess the data more completely."
The company also suspended a Phase II trial of Asentar in patients with advanced pancreatic cancer, he noted.
Following the analysis of the ASCENT-2 data, Walker said, Novacea and Schering-Plough will discuss the findings with the principal investigators and prostate cancer experts to "determine the possible causes for this outcome."
Walker assured investors that Novacea's financial position "is solid," with about $110 million in cash and receivables at the end of the third quarter, "which should help to withstand this setback and will not necessitate us going back to the capital markets in the near future."
He said the decision to stop the Phase III trial would not result in any immediate layoffs of Novacea employees.
"We have a lot of work ahead of us," Walker said, noting that aside from the analysis of the ASCENT-2 data, the company is continuing its expansion of studies of AQ4N, a hypoxia-activated prodrug that currently is in a Phase Ib/IIa clinical trial in glioblastoma multiforme and a Phase II trial for refractory acute lymphoblastic leukemia.
The firm also is pursuing its ongoing strategic initiative to broaden its product pipeline, he said.
Novacea's business development group, Walker added, "continues to be very active in evaluating new product candidates for in-licensing as well as a wide range of strategic business opportunities."
While the outcome for ASCENT-2 was "profoundly disappointing" for Novacea, Walker said, "we remain hopeful that Asentar has utility as a cancer treatment. We will work diligently with our partner Schering-Plough to fully understand the data and to prepare revised plans and resources for Asentar."
Because Novacea has remained blinded to the ASCENT-2 data, he noted, the firm is "presently unable to answer the many questions that all of us may have."
It could be "several months," Walker explained, before the company is able to share its findings from the analysis of the ASCENT-2 trial and the firm's future plans for Asentar.
But, he declared, Novacea remains "hopeful that Asentar could, one day, be a benefit to cancer patients."