Pharma’s Cutting Edge

You’ve by now read that Dendreon shares surged Friday following a Thursday meeting of a CBER advisory committee that indirectly endorsed FDA marketing approval for Dendreon’s first therapy, Sipuleucel-T (aka Provenge), an active immunotherapy for men with advanced hormone-refractory prostate cancer (HRPC).  If approved, Sipuleucel-T would be the first active cellular immunotherapy for cancer ever marketed. 

The method for producing Sipuleucel-T and its proposed mechanism of action is depicted in this slide adapted from a Dendreon presentation.  Each patient receives a treatment made from his or her own (i.e. autologous) antigen-presenting cells (APCs).  A treatment cycle will generally include three infusions of autologous APCs, at a cost estimated by one Dendreon consultant to be around $20,000 per infusion.

The advisory committee’s endorsement of Sipuleucel-T was based on its relatively benign safety profile (aside from a modestly increased risk of cerebrovascular accidents, the therapy was safe and tolerable) and the demonstration of a median survival advantage relative to placebo of about 4 months in one trial, allowing half the recipients of active therapy to live just over two years.  A second trial was associated with a trend towards improved survival. 

There are very few treatments for HRPC.  Probably the most frequently prescribed regimen in the U.S. is a combination of prednisone and docetaxel (Taxotere, Sanofi-Aventis).  This chemo regimen appears to be less well tolerated than Sipuleucel-T (although Dendreon made no direct comparison) and is associated with toxicities such as edema, liver damage, and neutropenia that have earned it a black box warning from FDA.  In exchange for its troubles, Taxotere added only 2.5 months median survival advantage to men with HRPC in its pivotal trial.  It’s not surprising then, that patients and doctors lament the lack of treatment choices for HRPC and are asking FDA to expedite approval of promising new therapies, Sipuleucel-T in particular.

I think FDA will use common sense and approve Dendreon’s therapy prior to completion of the ongoing 500-patient Phase 3b trial, which is now roughly 80% enrolled and is expected to report in 2010.  As one commenter noted, the drug seems safe and is reasonably well-tolerated.  If there’s a decent chance based on the results of one trial and an integrated analysis of efficacy that it will prolong survival why not approve it.  Sipuleucel-T promises no miracles, but when lifespan is measured in months, patients deserve a chance to add on a few.   

Okay, so all of the above is the good news.  The less good news is that treatment with Sipuleucel-T won’t cure men with HRPC, prevent their tumors from growing or their pain from returning, or return them to the workforce.  It’s also going to cost a pretty penny.  So, economically-speaking, treatment with Sipuleucel-T will be a perceptible, albeit relatively small, burden on U.S. federal healthcare outlays and perhaps on individuals who fall within coverage cracks or doughnut holes.   On the not-so-obvious front, should Sipuleucel-T become widely adopted and viewed as a standard-of-care that cannot be denied to patients with HRPC, it will make it more difficult for other drugs aimed at HRPC to be tested and approved.  Sponsors will likely have to recruit patients with more advanced disease, after they’ve failed Sipuleucel-T.  Remember, Sipuleucel-T is an active immunotherapy and probably cannot be used in conjunction with cytotoxic drugs that suppress T cell numbers or activity.

Dendreon may be on the cusp of bringing the first active immunotherapy for cancer to market after decades of basic research, 11 years of clinical testing and numerous failures by sponsors of other, similar therapies to do likewise.  It’s a momentous achievement.