Washington Editor

Intracel Corp. got the FDA's green light to begin a pivotal trial of OncoVAX in early stage colon cancer to confirm previously generated positive data on the long-investigated cancer vaccine.

The autologous product has "real deep roots," said Chief Operating Officer Peter Nardin, as does the company, which dates back about 30 years. These days, its principal efforts are focused on OncoVAX, which is approved in two European countries and has fast-track status from the FDA.

The randomized Phase III study will test the patient-specific tumor cell vaccine's ability to treat Stage II colon cancer in patients after their tumors have been surgically removed. That phase of the disease involves limited penetration of the tumor through the bowel wall and no involvement of the regional lymph nodes, but in about a third of those patients, the cancer returns, and does so metastatically.

"For patients diagnosed with Stage II colon cancer, the only approved therapy is surgery," Nardin told BioWorld Today. "No other drug, chemotherapy or radiation has proved to have any recurrent effect."

So the trial's primary endpoint is disease-free survival, and secondary endpoints include the recurrence-free interval and overall survival at five years.

Nardin said the company, of Frederick, Md., hopes the data replicate findings from an earlier Phase III study, which lasted 13 years and provided a glimpse at OncoVAX's potential. In that randomized trial, the personalized therapy reduced patients' five-year recurrence rate by 80 percent. Notably, a year and a half after surgery, only 4 percent of OncoVAX-treated patients experienced recurrence, while the cancer came back in 23 percent of those in the control arm, who had surgery only.

The product is intended to treat patients at earlier than most approved therapies. Other therapeutic agents are cleared for the adjuvant treatment of Stage III and Stage IV colon cancer, but none are available for Stage II.

Enrollment of 560 patients is expected to begin in June and take two years, during which time half will get OncoVAX after surgery and the remainder will have surgery only, and the primary analysis will take place three years later.

An interim analysis will be performed one year following randomization of the last patient, which Nardin said should generate data that are "sufficiently robust to allow us to file" a biologics license application at that point. In the near term, he added, Intracel plans to begin submitting early components of the BLA on a rolling basis.

The trial, for which the company has a special protocol assessment agreement with the FDA, will be conducted throughout the U.S., UK, the Netherlands and Germany. The immunotherapy involves a vaccine made from a patient's tumor cells, which are dissociated, irradiated and administered in three injections given a week apart, starting about a month after surgery. Cells in the first two vaccines are mixed with Bacillus Calmette-Guérin (BCG), a Mycobacterium strain that acts as an immune stimulant. A booster vaccination is administered six months later.

"It excites the combination of the tumor cells," Nardin said, "and the adjuvant excites the immune system."

Through OncoVAX's development, manufacturing issues had to be resolved. Principally, the FDA had concerns about sterility, "one of the biggest issues we've had to face," Nardin said. Additional challenges related to the product's potency. But in time, the company was able to produce a consistently sterile vaccine that has uniform potency, identity and characterization.

OncoVAX is approved in the Netherlands and Switzerland. About 240,000 colon cancer cases are diagnosed annually in the U.S. and Western Europe, and the proportion of patients first presenting with Stage II disease has been increasing over the last decade, due in large part to what Nardin termed "great awareness campaigns" that have led to greater use of diagnostic tests such as sigmoidoscopy and colonoscopy.

In addition to colon cancer, Intracel is eyeing additional uses for the product, "all applicable to early stage disease," Nardin said. Already, the company has completed Phase I/II studies of OncoVAX in melanoma, renal and ovarian cancer, and a Phase II/III trial is likely to begin by the end of this year.

Eventually, Intracel might partner the product, though such decisions remain market-dependent.

Intracel, which went bankrupt in September 2001, came back to life with a $16 million funding round a little more than three years ago. Since then, it has recapitalized with two additional private equity rounds that were not publicized. (See BioWorld Today, Dec. 13, 2002.)