Dendreon surges on Provenge hope

Shares in Dendreon have increased dramatically over the past few days, possibly as the result of investors trying to cash in before the company releases final results from its make-or-break IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment; also known as D9902B) study. The trial is designed to assess the safety and efficacy of the investigational active cellular immunotherapy, Provenge (sipuleucel-T), in men with metastatic androgen-independent prostate cancer (PCA). Dendreon’s shares closed at US$4.05 on 13th March, up 46 per cent on the closing price on 11th March of US$2.77.

The latest price increase was likely triggered by the release of Dendreon’s fourth quarter and 2008 year-end financial results on 12th March, confirming that it anticipates the IMPACT study to continue to its final analysis, which is expected to be completed by the end of April. Favourable blinded, interim results from the trial were previously reported in October 2008, when the independent Data Monitoring Committee (IDMC), which is overseeing the trial, recorded a 20 per cent reduction in the risk of death in the Provenge arm relative to placebo (hazard ratio=0.80; 95% CI, 0.610 to 1.051). The IDMC observed no safety concerns and recommended that the study continues as planned. However, at that time the company only announced that the final analysis was anticipated in the middle of 2009.

At the final analysis, if the study demonstrates approximately a 22 per cent reduction in the risk of death, based on 304 events, the company would expect the trial to meet its primary endpoint of overall survival (OS). Should the prespecified criterion for statistical significance be achieved, Dendreon would anticipate amending its BLA based on these interim results. The initial BLA filing was based primarily on an improvement in OS observed in the Phase III D9901 trial. Following an FDA Advisory Committee vote that there was substantial evidence of efficacy of Provenge and that it was reasonably safe, the Agency requested additional clinical data to support the proposed efficacy claim. The FDA has since indicated that either a positive interim or final analysis for OS from the IMPACT trial would be sufficient to address the request for additional information to support the proposed efficacy claim.

Sipuleucel-T contains mature, autologous antigen presenting cells (APCs) that are obtained from the patient via a standard procedure approximately two days before each scheduled infusion. The patient's APCs are then transported to a Dendreon manufacturing facility where they are co-cultured with a recombinant fusion protein containing prostatic acid phosphatase. The activated, antigen-loaded APCs (now sipuleucel-T) are then delivered to the physician's office for infusion into the patient. Sipuleucel-T is then infused into the patient, where it can potentially stimulate a T-cell response against PCA cells. Well, that is the theory anyway, and investors buying up Dendreon’s shares will hope that is also the case in the IMPACT study. They will also have their fingers crossed that the company can hit the heady heights of April 2007, when its shares reached US$23.58.

Matthew Dennis - Editor, Cancer Drug News