Dendreon's Provenge (sipuleucel-T) faces a rocky road ahead following the company's announcement of its second quarter 2011 financial results. What does the future hold?

On August 3, 2011, Dendreon reported net revenue of $78 million for the first half of 2011 (ending June 30, 2011), representing a significant a significant reduction on company forecast for Provenge. Consequently, the company withdrew its prior forecast of $350-400 million for 2011, but rather expects modest growth for the remainder of the year without being too specific as to their 2011 sales expectations.

Provenge became the first personalized therapeutic vaccine to gain major market regulatory approval for any oncology indication in April 2010. The path to regulatory approval was turbulent. Success in gaining FDA approval was however widely regarded as a milestone in clinical development for both prostate cancer and the field of oncology. At the time of FDA approval there was much enthusiasm and optimism for this novel agent and within the first year following its approval there has been high patient demand. However, penetration of the prostate cancer market has been slow, not least because of Dendreon's limited patient-specific manufacturing capabilities. Although manufacturing constraints for Provenge now appear to have been alleviated, growth in sales has been considerably lower than expected.

Dendreon primarily attributed a lower 2011 sales projection to cautious physician prescribing, especially in the community setting, due to physician concern over gaining reimbursement for this highly priced therapy. The company stated that the high cost density associated with Provenge (i.e., Provenge's high price [$93,000] and administration over a short period of time [one month]) has created considerable reimbursement uncertainty among physicians. This is so, even though the Centers for Medicare & Medicaid Services (CMS) recommended that Provenge be covered nationally for all Medicare beneficiaries according to the FDA approved label, in June 2011. Unless physicians gain more confidence that they can be reimbursed for the cost of Provenge, and quickly, it is likely that the high cost of this novel therapeutic and the current reimbursement environment will be prohibitive in its uptake. Indeed, physicians and payers surveyed by Decision Resources reveal that the high price of Provenge and its patchy insurance coverage is a barrier to uptake1.

Although clinical data supporting Provenge as a first-line treatment for asymptomatic and minimally symptomatic castrate-resistant prostate cancer (mCRPC) are robust, Provenge has failed to demonstrate a significant improvement in time to disease progression over placebo. As such, the time to the requirement to treat with chemotherapy for symptomatic disease is likely not significantly different with Provenge treatment than with placebo. Experts interviewed by Decision Resources tell us that there is a subset of patients who are deterred from receiving Provenge, with this knowledge. Furthermore, there is no way of assessing which patients will most likely benefit from Provenge. These issues also likely contributed to the slower than anticipated uptake of Provenge, and are unlikely to remain unresolved in the near future.

The announcement of lower than anticipated sales is undoubtedly a setback for Dendreon, and the company faces a challenging time ahead. In addition to addressing physician confidence in Provenge's reimbursement environment, other novel therapeutic agents are on the horizon and are poised to threaten Provenge's current position in the prostate treatment paradigm. Most notably, Johnson & Johnson's Zytiga (abiraterone)  FDA approved in April 2011 as a treatment for mCRPC patients who have received prior docetaxel (Sanofi's Taxotere)  is being assessed as a treatment for the same subset of patients that Provenge is approved for. If Zytiga significantly improves overall survival and progression-free survival, and we expect that it will do, this novel hormonal agent could hit Provenge hard. Pivotal Phase III data for Zytiga in the first-line mCRPC setting is eagerly awaited.

There are perhaps now more questions than answers about the future of Provenge. Not least, with significant investment in a European manufacturing site, what does the future hold for Provenge in Europe Lower than anticipated sales of Provenge in the United States certainly do not bode well for sales of Provenge in more cost-constrained European markets. However, there are likely many lessons learned from the developmental and commercial pathway of Provenge, and its woes post-approval. Developers of therapeutic vaccines in particularly for prostate cancer and other oncology indications could gain much from recent events.

1 U.S. Physician and Payer Perspectives on Provenge, the First Therapeutic Cancer Vaccine: The Proof is in the Prescribing. Decision Resources, Inc. Physician and Payer Forum, June 2011.

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