The FDA's nod of approval in hand, Tularik Inc. is moving forward with its pivotal trial program for T67.

The agency signed off on the South San Francisco-based firm's study design for its lead anticancer drug for patients suffering from hepatocellular carcinoma (HCC). Tularik said the FDA's positive feedback negated a need for an end-of-Phase II meeting.

"The primary endpoint will be survival," Director of Investor Relations Traci McCarty said. "As a pivotal trial, there are early stopping rules in place. Our goal is to enroll 750 patients, but when we enroll a certain undisclosed number, we're going to take a look at all the data in hand."

She said the interim analysis would examine the drug's safety, efficacy and alpha-fetoprotein levels.

"If the data are turning in the right direction, an outside panel of experts will decide if we will continue to move forward," McCarty said.

The pivotal Phase II/III trial will be performed at numerous centers across the U.S., Europe and Asia. Its planned design will compare survival in patients who receive T67 at a dose of 250mg/m² given by intravenous infusion every week to doxorubicin at a dose of 60mg/m² given by intravenous infusion every three weeks.

T67's dose increase, from a Phase II level of 165mg/m² administered intravenously weekly, is based on low incidence of adverse events and hematologic toxicity, as well as related pharmacokinetic analysis.

At the meeting of the American Society of Clinical Oncology in May, Tularik reported that three of 34 unresectable HCC patients had partial responses and 38 percent (13 of 34) had stable disease. Also, five of 27 evaluable patients had a more than 50 percent reduction in alpha-fetoprotein.

With more than 260 patients dosed to date, Tularik said the drug has shown objective partial responses, defined as greater than 50 percent reduction in tumor size.

T67 binds irreversibly to beta-tubulin, a cellular building block of microtubules needed for cell division, making it a clinically proven cancer target, Tularik said. McCarty said the drug's irreversibly binding characteristics differentiate it from other tubulin-binding agents.

The upcoming study is aimed at evaluating the drug's safety and efficacy in patients with cancer related to hepatitis C infection. Its aggressive malignancy results in a six-month survival rate of 50 percent from time of diagnosis. HCC's one-year survival rate is 24 percent and the five-year survival rate is less than 5 percent.

Tularik expects to begin the trial early next year, though McCarty said exact timeline details were difficult to specify.

"It's really a function of where we end up enrolling the patients," she said. "There are different regulatory procedures in Europe and Asia, so it's really difficult to call right now."

Tularik, which retains complete worldwide rights to T67, said its platform spans seven disease-based programs focused on three areas: cancer, immunology and metabolic disease.

Its other drug in the clinic is T607, an analogue of T67, for which Tularik has begun Phase II trials in HCC, non-Hodgkin's lymphoma, gastric cancer and ovarian cancer.

Two months ago, the company dropped its development of two compounds - T611 for cytomegalovirus,outside of Tularik's area of focus, and the anticancer drug T64, for competitive reasons. (See BioWorld Today, June 12, 2002.)

Tularik's stock (NASDAQ:TLRK) climbed 46 cents Tuesday to close at $7.96.