BioWorld International Correspondent

Austrianova Biotechnology GmbH aims to commence a Phase III trial of an encapsulated cell therapy in pancreatic cancer at the beginning of 2007, having recently attained good manufacturing practice compliance for the product, called NovaCaps.

The Vienna, Austria-based company said it believes it is the first in the world to attain GMP compliance in this area.

"It's very difficult to get reproducible encapsulation of cells," Austrianova co-CEO Brian Salmons told BioWorld International. "We went from a batch process to a continuous process. That was a major advance."

The latter achievement has streamlined the production process and eliminated additional tests required to support batch pooling, he said.

The company invested €6 million (US$7.7 million) over the past two and a half years in building up its capabilities in this area. It now has capacity for producing up to 40,000 vials annually - enough, it stated, to meet expected demand. Its manufacturing partner, Miltenyi Biotec GmbH, of Bergisch Gladbach, Germany, participated in the process development work.

Austrianova now is in a position to license the technology to third parties, Salmons said, and the company already has held exploratory discussions with potential partners while on a recent tour to Australia and Singapore.

Meanwhile, it is moving ahead with its Phase III pivotal trial of the pancreatic cancer therapy, which has obtained orphan drug designation from the European Union's drug regulator, the London-based European Medicines Agency. Some 200 patients will be recruited in centers located in several European countries.

The study will evaluate survival advantage for patients with inoperable pancreatic cancer in receipt of the therapy, which is designed to boost levels of the pharmacologically active metabolites of the prodrug ifosfamide.

The therapy comprises systemic administration of ifosfamide along with localized delivery of encapsulated HEK 293 cells that are engineered to express cytochrome P450, a liver enzyme that converts the prodrug into an unstable intermediate, 4-hydroxyifosfamide, which can enter cells.

Once inside the cell, that spontaneously decays to form phosphoramide mustard and acrolein, which alkylate DNA and proteins, respectively, and thereby exert antitumor effects. Classical ifosfamide therapy is limited by toxicity problems. As the pancreas is the final organ to drain into the liver, only low levels of 4-hydroxyifosfamide are available to enter tumor cells located in the pancreas.

The encapsulated cells are delivered to the head of the pancreas, where most tumors form, via arterial catheterization. Because of their proximity to the cancerous cells, only one-third of the usual dose of ifosfamide is administered.

"It's an important facet of the whole treatment that we're going in with a low-dose therapeutic," Salmons said.

The company reported median survival of 40 weeks in a Phase I/II trial, double that normally associated with classical ifosfamide therapy.

Since completing that trial, Gemzar (gemcitabine), marketed by Eli Lilly and Co., of Indianapolis, has become the gold standard therapy for pancreatic cancer, Salmons said, yet its reported median survival is just 25 to 26 weeks.

Moreover, reported data for Gemzar indicated a one-year survival frequency of 18 percent, whereas Austrianova obtained a one-year survival rate of 36 percent in its study, albeit with a small sample size, he said.

Austrianova was formed as a spinout from the University of Veterinary Medicine in Vienna in 2001. The company has raised €16 million to date.

"We're in a financing round at the moment. We're looking to raise something from €20 million to €25 million," Salmons said.