Dendreon Biopharmaceutical Manufacturing Plant, Seattle, USA

Dendreon Corporation is a US biotechnology company based in Seattle currently in the spotlight over their controversial cancer vaccine for the treatment of prostate cancer, which is the third most prevalent cancer worldwide, causing over 40,000 male deaths a year in the US and UK.

In 2005 Dendreon began the construction of a new manufacturing plant in New Jersey to produce its investigational active cellular immunotherapy (Provenge vaccine) for advanced prostate cancer.

The plant was topped out in August 2006 with the fit-out completed in June 2007. In May 2007 the US FDA (Food and Drug Administration) proved less enthusiastic about Dendreon’s new treatment than expected, which has led to a scaling down of the manufacturing plant from 48 to 12 cleanrooms (with associated laboratory support) and a drop in company share prices.

The FDA has issued Dendreon an approvable letter but it needs to present more data for the efficacy of Provenge. Preliminary results will be available from a 500 patient clinical trial in 2008 with full results available in 2010.

This clinical trial has been designed to show that Provenge extends life expectancy when given to men whose prostate cancer has metastasised to other parts of their bodies. These cases would not have a good prognosis with current treatments, and if this trial is positive, it could be enough for the FDA to allow the drug to be put into commercial production.

PROVENGE VACCINE FOR PROSTATE CANCER TREATMENT

Dendreon is working on the development of novel therapeutics that harness the immune system to fight cancer. The company has strong experience in antigen identification, antigen engineering and antigen-presenting cell processing and this has led to compounds capable of causing a cell-mediated immune response.

Provenge (sipuleucel-T) is the company’s lead active cellular immunotherapy which is currently in Phase 3 development for treatment of advanced hormone-refractory prostate cancer. Provenge targets the prostate cancer antigen, prostatic acid phosphatase (PAP), which is found in approximately 95% of prostate cancers. They also have Trp-p8, a cold receptor and transmembrane ion channel in preclinical development, which is over-expressed in breast, prostate, lung and colon cancers.

DENDREON PLANT CONSTRUCTION

The new plant was constructed by the Henderson Corporation with architectural services supplied by Perkins & Will. Although the plant construction was completed in August 2006 the fit-out was scaled down in June 2007 and the plant capacity will be smaller than expected.

"This was part of their efforts to shift resources to prepare for the regulatory application and commercialization of Provenge." Mitchell H Gold, president and chief executive officer of Dendreon said at a recent press conference about the new plant: "We are committed to bringing Provenge to the market to help the many men with late-stage prostate cancer and believe this achievement brings us one step closer to this goal."

PROVENGE TECHNOLOGY

Provenge is delivered using proprietary antigen delivery cassette technology, which uses a recombinant form of an antigen found in approximately 95% of prostate cancers, prostatic acid phosphatase (PAP), to stimulate the patient's immune system to attack the cancer cells.

In March 2006 Diosynth were awarded a long-term contract by Dendreon to produce the recombinant protein antigen component of the new Provenge therapy.

Diosynth has already been producing the recombinant protein antigen component of the product on a small scale to supply clinical trials from its North Carolina plant and is ready to scale up manufacturing capacity to meet expected commercial demand.

LICENSING

In 2006 Provenge was given a Fast Track designation and Dendreon submitted a Biologics License Application (BLA) to the FDA as a rolling submission for approval to market. They intended to apply for Priority Review upon completion of the BLA submission.

The company received notice of approval from an FDA panel in March 2007. However, following criticism from two experts that the clinical studies were too small, in May 2007 the FDA asked for more evidence. Dendreon now faces the prospect of having to wait several years to gather enough supporting data from larger trials to support the Provenge application.

This may require more funding and may result in the company returning to the market to raise capital or alternatively being bought by a larger company with more resources. Provenge is a potential blockbuster treatment but as a new class of drug its efficacy needs to be above reproach.

Meanwhile, prostate cancer patients and investors in Dendreon are lobbying the FDA to approve Provenge. The FDA has also been sued for withholding approval of the drug.