If the sipuleucel-T story were a movie, it would have most of the elements of a blockbuster: money, power, conflict, ethics, and even death threats.
What the prostate cancer vaccine doesn’t have, at least not yet, is the Hollywood ending: the "ah-ha" moment when the protagonist – in this case the first autologous cellular immunotherapy approved for any oncology indication – overcomes unbelievable odds and revolutionizes cancer treatment.
Instead, the momentum that propelled sipuleucel-T along the turbulent path to regulatory approval in April 2010 seems to have stalled. Acceptance in the prostate cancer market has been slower than expected, as sales fell substantially short of consensus estimates for the second quarter. Market analysts are skewering the manufacturer, Dendreon, for grossly overinflating expectations, and, at least in the business sector, the company’s claims that reimbursement concerns are at the root of the sluggish numbers seem to be falling on deaf ears.
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Most physicians have strong opinions on sipuleucel-T, including dubbing its approval "a milestone in the history of oncology," but many of them refuse to even speak about it on the record.
Terms such as "implosion" and "derailment" in the business press have the ominous tone of a death knell for sipuleucel-T (Provenge), but oncologists and urologists in the trenches are more forgiving, albeit reasonably cautious. In an ironic twist, interviews show they want more data – a complaint that has dogged sipuleucel-T since the 2007 decision by the Food and Drug Administration’s Center for Biologics Evaluation and Research to act against its advisory panel’s favorable recommendations.
Instead of approval, the agency sent a complete response letter requesting further clinical evidence. Patient and lobbyist picketing outside of FDA offices and cancer conferences, death threats to panelists who had resisted approval, calls for congressional inquiries, and a lawsuit grabbed headlines but did not reverse the decision.
And even after the indication was won, though a Centers for Medicare & Medicaid Services (CMS) panel voted in favor of national coverage for all Medicare beneficiaries beginning July 1 of this year, the panelists expressed only intermediate confidence that the immunotherapy was safe and effective for its labeled indication and very low confidence on off-label use.
Against this backdrop, perhaps it is not surprising that, of 16 physicians approached for this article, many had strong opinions but only a few would speak on the record.
Paradigm Advance Called Huge
Dr. Philip Kantoff, lead author of the pivotal phase-III IMPACT trial in which sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer, maintains that the treatment "represents a huge paradigm advance and is a significant advance for prostate cancer patients."
In the IMPACT trial, sipuleucel-T was associated with a median 4.1-month increase in patient survival, compared with patients in the control condition (25.8 months vs. 21.7 months). The 36-month survival probability in the sipuleucel-T group was estimated to be 31.7%, compared with 23.0% in the placebo group, the investigators reported (N. Engl. J. Med. 2010;363:411-22).
Although many have suggested that the cost of the treatment, at $93,000, may be a barrier to adoption, given the seemingly modest survival benefit in the absence of any prostate-specific antigen (PSA) changes or time-to-disease progression benefit, Dr. Kantoff disagrees. He suggests that it is the fears over timely reimbursement and not the cost of the treatment that is keeping many clinicians from taking the plunge.
"The cost [of sipuleucel-T] treatment is comparable to other cancer therapies; the difference is it is given over a 4-week period rather than over many months," Dr. Kantoff, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute in Boston, said in an interview.
The "cost-density" of the treatment, rather than the overall cost per se, combined with the requirement by some private payers for special coverage authorization, might be keeping some clinicians from jumping on board, at least until they are more confident in the reimbursement process, he said.
Dendreon has also cited cost-density as an important contributing factor to sipuleucel-T’s lower-than-predicted uptake among clinicians. The company’s Aug. 3, 2011 and Sept. 8, 2011 press releases, in which it reported second-quarter performance statistics and the corporate restructuring plan to compensate for the lack of anticipated growth, respectively, stated that the "primary issue affecting the dynamics of our launch is the reimbursement knowledge around [sipuleucel-T]."
Both communications suggested that the National Coverage Determination (NCD) issued by CMS and assignment of a Q code will lead to increased physician adoption over time.
The direct costs of the treatment, as well as the indirect costs in terms of staff time needed to arrange preauthorization and administer the infusions (three doses at 2-week intervals, with each dose preceded by the leukapheresis procedure 3 days prior), are obvious concerns. Clarifying the reimbursement picture is important, but it will hardly address all of the reasons urologists and oncologists might be reluctant to prescribe sipuleucel-T to their patients.