LONDON – Cancer specialist Activartis Biotech GmbH will present positive survival data from the Phase II trial of its dendritic cell therapy in treating glioblastoma at the American Association of Cancer Research (AACR) Wednesday, as it steps up efforts to find a partner to back a Phase III study.

The first interim analysis of the open-label, 100-patient trial indicated that when the final numbers are in there will be an overall survival benefit in patients treated with AV0113, which consists of dendritic cells loaded with antigens derived from each patient's tumor.

Thomas Felzmann, CEO, told BioWorld International that the safety profile and evidence of benefit is so compelling that the company is now seeking scientific advice from the regulators with a view to starting a compassionate use program in patients who do not meet the study criteria and in securing a conditional marketing approval from the European Medicines Agency (EMA). Earlier this year, AV0113 was awarded orphan drug status by the EMA

While autologous dendritic cell therapy has been validated by Dendreon Inc.'s Provenge (sipuleucel-T) treatment for prostate cancer, Activartis' technology involves supercharging the dendritic cells with a bacterial lipopolysaccharide. That acts as a danger signal, prompting the dendritic cells to release interleukin-12 (IL-12), and thus activating cytotoxic T lymphocytes.

"Although others – for example, [Northwest Biotherapeutics Inc.] –are now doing similar things, we were the first to do it and have intellectual property around the use of microbial proteins to polarize the immune system," Felzmann said. The platform technology is protected by patents describing the use of dendritic cells that are treated to promote the production of IL-12, and are loaded with tumor-specific antigens.

Alongside the Phase II evidence of safety and efficacy in glioblastoma, Activartis has evidence from academic clinical trials demonstrating the technology is applicable to other tumor types. Six of 25 pediatric patients with a range of advanced cancers who had failed all other therapies remain alive after treatment with AV0113, as do four of 13 late-stage kidney cancer patients and three of 15 bone cancer patients.

"We need a partner to move into a Phase III [in glioblastoma] and to take this forward in other kinds of cancer," Felzmann said. "We don't have the financial strength to bring these products to market ourselves." Activartis spun out of the St. Anna Children's Cancer Research Center in Vienna, Austria, in 2003 (then under the name Trimed) and in 2006 was acquired by the Austrian orphan drug company AOP Orphan Pharmaceuticals, which has since financed development of AV0113.

It has taken more than a decade from the filing of the first patent on the AV0113 technology in 2002, to the presentation of the glioblastoma data at the AACR meeting in Washington. Felzmann explained that in part was due to the previous lack of a regulatory pathway for a cell-based product of this type – with the year it took for the EMA to decide that it should be classified as a medicine and not a transplant, being one example of the bureaucratic longeurs along the way.

The first patient in the glioblastoma trial was treated in May 2010, and to date just more than 100 patients have received the therapy at centers across Austria. Glioblastoma is the most aggressive form of brain cancer with patients having an average progression-free survival of only seven months to eight months and overall survival of 14 months to 15 months. The interim data being presented by Felzmann at AACR show overall survival at 18 months for 50 percent of patients (8/15) in the treated arm, vs. 33 percent (6/18) in the control group.

Felzmann said that initially swelling in the brain caused by the immune response to antigen-loaded dendritic cells can cause symptoms, such as seizures, to intensify in the treatment arm. In addition, it takes time for the immune response to become established and to begin to show an effect in controlling tumor growth, and as a result (and in common with similar studies), there is no improvement in progression-free survival between the two arms of the glioblastoma trial. In contrast, overall survival "clearly is prolonged," Felzmann said.