Dendreon has already provided the Centers for Medicare and Medicaid Services with extensive information on its new prostate cancer vaccine Provenge (sipuleucel-T), so a lengthy Medicare national coverage analysis is not needed, the firm maintained in July 27 comments to the agency.

The comments respond to CMS' recent announcement that it would open an NCA to determine whether treatment with the breakthrough autologous immunotherapy should be considered "reasonable and necessary" for Medicare coverage (¹ Also see "Is Provenge "Reasonable And Necessary"? CMS Analysis For Medicare Coverage Seeks To Find Out" - Pink Sheet, 1 July, 2010.). The NCA may lead to a national coverage determination, with possible restrictions on reimbursement for the therapy.

Dendreon's submission underscores the question of how drug developers can effectively engage with CMS to ensure Medicare coverage of new products as they undergo review at FDA. Provenge was approved by FDA April 29, and CMS opened the NCA on June 30.

"Dendreon appreciates the numerous opportunities we have had to meet with [CMS] to discuss Provenge both pre- and post- FDA approval," the company said. "We believe that the agency should be very familiar with Provenge's clinical benefits and manufacturing process as a result of these meetings and all of the additional information we have provided in other various forms."

For example, Dendreon said it submitted substantial clinical and product information to CMS to facilitate Medicare coverage in its applications for a Healthcare Common Procedure Coding System reimbursement code and pass-through biological status under the hospital outpatient prospective payment system.

Acceptance Among Medicare Contractors

Furthermore, the company said, early variation in local Medicare coverage policies for Provenge has diminished, eliminating the need for a national decision that would standardize reimbursement. "Currently most Medicare contractors have published guidelines or verbally indicated they are/will cover Provenge as a biological product for its on-label indication."

Therefore, Dendreon argued CMS should either close the NCA or conclude it quickly by determining Medicare should cover Provenge for its approved indication - treatment of asymptomatic or minimally asymptomatic metastatic castrate-resistant prostate cancer.

The firm also urged the agency to forgo plans for a contracted technology assessment on Provenge, as well as a Medicare Evidence Development and Coverage Advisory Committee review. The Agency for Healthcare Research and Quality is planning to conduct the technology assessment on health outcomes for sipuleucel-T.

To allow time for the technology assessment, CMS has announced plans to take up to a year (to June 30, 2011) to make a final decision on Provenge, a period of uncertainty that could impair early market acceptance of the therapy.

Along with its comments, Dendreon provided CMS with a copy of the Phase III clinical trial that was pivotal in the vaccine's approval. Published in the New England Journal of Medicine July 29, the study concludes the immunotherapy significantly prolonged survival in 512 men with metastatic castration-resistant prostate cancer. It was completed after two smaller trials, which FDA did not consider adequate to support approval.

However, an accompanying editorial reflects the current wariness about the study among health professionals. Physician Dan Longo writes that the surprising finding that tumor progression was not affected by Provenge raises questions about the study design.

The editorial also notes that the high cost of the therapy "may affect use," adding: "It is also uncertain what role sipuleucel-T will ultimately play in the treatment of prostate cancer, given the other promising treatments in development." Longo summarized his concerns in comments to CMS on the NCA.

Although the price of the therapy, $93,000 a course, has gotten a lot of attention, CMS is not permitted to consider cost in its coverage decisions. However, the level of evidence supporting the approval may be cause for concern. Provenge's effectiveness was ultimately considered to be proven in the one clinical trial and there was no confirmatory follow-up study (² Also see "Provenge Panel's Uncertainty Was More Persuasive To FDA Than Its Vote" - Pink Sheet, 1 June, 2010.).

"Shockwave" To Biotech Investing

Nevertheless, the tension set up by CMS potentially second-guessing FDA on Provenge has prompted the financial community to weigh in on the NCA.

Robert Brookby, of Putnam Investments, stated in comments that "to have a non-scientific agency essentially intervene with the possibility of not covering this drug after it has successfully exhausted the long road to commerciality is a shockwave of risk to all biotech investing."

He warned the CMS action "is likely to adversely affect capital formation and capital availability to the biotech industry if investors now cannot depend on the FDA as being the final arbiter of safe and effective drugs."

Adding the uncertainty of "'what does CMS think of the drug's reasonableness and necessity' is another huge risk factor that will depress investor interest in funding the most novel drugs of the future," Brookby said.

CMS: The New Social Media?

The high profile nature of the agency's coverage analysis is reflected in an unusual interplay between the comments posted to the CMS Web site. A number of commenters submitted more than one entry, sometimes responding directly to other comments, with the result that the assembly of comments looks more like a social media site than a regulatory forum.

Most of the comments appear to be concerned individuals, and many are physicians or representatives of health care organizations or patient advocacy groups.

One comment supporting Medicare coverage, submitted by an individual July 29, begins: "For any new readers of the Provenge Comments page or those just checking again, a few summary thoughts that will hopefully answer any lingering basic questions."

The commenter also provides "a list of selected comments on this page, all supportive of Provenge, which hopefully would provide any reader with questions, doubts, etc. about Provenge more than sufficient information and reason to reconsider their view."

- Cathy Kelly ( ³ c.kelly@elsevier.com )

Provenge Should Be "Very Familiar" To CMS Now, Dendreon Says About NCA

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