Provenge Off-Label Use Is Key CMS Concern In NCA, Dendreon Says

In its ongoing national coverage analysis of Dendreon's Provenge (sipuleucel-T), the Centers for Medicare and Medicaid Services is taking a close look at Medicare coverage for off-label use of the novel prostate cancer vaccine, according to the company.

Dendreon discussed the NCA, as well as early sales for the autologous immunotherapy, during its second quarter earnings call Aug. 3 ¹ (Also see "Provenge Tops 500 Scripts Since Approval; Most Local Medicare Contractors Will Cover Product" - Pink Sheet, 3 Aug, 2010.)). Reimbursement decisions for the physician-infused product are being watched carefully by investors since Provenge has a price tag of $93,000 for each three-dose course of treatment.

Chief Operating Officer Hans Bishop said that "one of the things we believe is important to [CMS] is to really understand how to define the on-label versus off-label population, and that's something clearly we'll be working with them to make sure they understand how we see it over the next several weeks."

Provenge is approved for treating asymptomatic or minimally symptomatic prostate cancer that is metastatic and resistant to standard hormone treatment. The potential for use in earlier stages of the disease is the off-label opportunity. For example, it could help after surgery for men with no overt metastases but who are at risk for developing them.

The on-label indication reflects the patient population in the pivotal clinical trial that formed the basis for the vaccine's approval. However, FDA earlier gave serious consideration to a broader indication, agency review documents for Provenge show (² Pharmaceutical Approvals Monthly, June 1, 2010).

The original indication proposed in the Provenge licensing application was broader: "for the treatment of men with metastatic castrate resistant (hormone refractory) prostate cancer."

And during the review, the Center for Biologics Evaluation and Research review team gave "thorough consideration" to the broader indication, Provenge Review Committee Chair Thomas Finn reported in the April 29 summary basis of approval. In the end, given the novelty of the therapy, FDA took the conservative route and narrowed the indication to the types of patients studied.

Dendreon said it cannot provide a breakdown on how many of the prescriptions written to date for Provenge have been for off-label use. "That's a question that is ultimately in the hands of the doctor," Bishop said during the earnings call.

Dendreon expects that CMS will, as announced, take 11 months to conduct the coverage analysis, which will include a technology assessment and a Medicare Evidence Development and Coverage Advisory Committee review. The process may lead to a national coverage determination that could limit Medicare reimbursement for the vaccine.

"We're planning [that] the process will see its way all the way through to the end on the time lines [CMS has] declared," Bishop commented. In recent comments to the agency, Dendreon had urged CMS to either cancel the NCA or foreshorten the process ³ (Also see "Provenge Should Be "Very Familiar" To CMS Now, Dendreon Says About NCA" - Pink Sheet, 2 Aug, 2010.)).

A proposed decision is scheduled to be issued by CMS March 3, 2011 and a final decision by June 30, 2011.

In the meantime, Provenge has achieved broad reimbursement acceptance by local Medicare Administrative Contractors, the firm reported. Local carriers determine Part B coverage in their regions in the absence of a national coverage decision.

Most Local Medicare Contractors Will Cover

So far, nine MACs have published positive coverage guidelines, another three have issued written confirmation of coverage to physicians and two have given verbal confirmation of coverage, it said. Only one MAC has issued a non-coverage decision.

In addition, a number of large private payers such as Aetna, Emblem Health, Humana, Kaiser Permanente and many Blues plans are covering Provenge, the company said. WellPoint also said it is covering the product.

Dendreon highlighted the strong endorsement of Provenge in the National Comprehensive Cancer Network's medical practice compendium as a positive development for its reimbursement prospects (⁴ (Also see "Provenge Poised For Broad Insurance Coverage, Despite Grumbles On Price" - Pink Sheet, 24 May, 2010.)).

Specifically, the NCCN guidelines state that sipuleucel-T is appropriate as salvage treatment for patients with castration-resistant prostate cancer who have minimally symptomatic disease, and a life expectancy of at least 6 months.

More than 500 prescriptions have been written for Dendreon's Provenge since it was approved on April 29, the company said. Dendreon also reaffirmed previous guidance that it expects 2,000 prescriptions for the prostate cancer vaccine in its first 12 months on the market.

The script target assumes the company will be able to expand production in its New Jersey facility by early 2011, the company explained. Currently the sole source for Provenge, the facility is operating at 25 percent capacity (⁵ (Also see "Dendreon Readies For Next Provenge Hurdles: Supply And Reimbursement" - Pink Sheet, 3 May, 2010.)).

"This number relies on the additional capacity becoming available following the buildout and subsequent regulatory approval of the remaining 75 percent of our New Jersey facility. And so, a significant percentage of these 2,000 patients will be treated early in 2011," Dendreon President Mitchell Gold said.

The firm also is planning to have its facilities in Atlanta and Los Angeles producing Provenge by the middle of 2011.

Manufacturing is a big challenge for the immunotherapy, as each dose is produced specifically for a particular patient using the patient's own cells. With Provenge, the patient's immune cells are altered via leukapheresis to boost their ability to fight prostate cancer. Then the activated immune cells are delivered back intravenously to the patient.

The company reported revenues of $2.8 million for Provenge in the quarter ending in June, with most of those sales in June, since May was the "start-up" month for the product, the company said. Dendreon added that revenues have continued to climb since the end of the quarter, reaching $5.2 million in July.

- Cathy Kelly ( ⁶ [email protected] ) and Scott Steinke ( ⁷ [email protected] )