Washington Editor

WASHINGTON – Most analysts agreed that the 3.6 intermediate confidence score in overall survival from Wednesday's Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) bodes well for Dendreon Corp.'s Provenge (sipuleucel-T) as the government hashes out whether the prostate cancer immunotherapy is a "reasonable and necessary" medication for Medicare beneficiaries.

Investors thought so, too – pushing shares of the Seattle-based biotech (NASDAQ:DNDN) up nearly 10 percent Thursday, before closing at $38.23, a gain of $2.36, or 6.6 percent.

The MEDCAC also gave high marks for Provenge in avoiding or minimizing the burdens of anticancer therapy, while maintaining overall survival and control of disease-related symptoms, doling out a 3.1 on the panel's confidence scale, with 5 being the highest.

Provenge had to meet at least a 2.5 confidence score in an initial question before the MEDCAC could make its determinations on those outcome questions, with panelists giving the immunotherapy a 3.7 ranking for overall survival and 3.9 score on the medicine's ability to avoid or minimize burdens of anticancer therapy.

Provenge, however, failed to meet that 2.5 mean in the initial round about its ability to control disease-related symptoms, only gaining a 2 on the confidence ranking. So no final question was asked on that outcome.

Historically, a 2.5 or higher score on a question suggests Medicare will reimburse a product, said Deutsche Bank Equity Research analyst Robyn Karnauskas.

The Centers for Medicare & Medicaid Services (CMS) convened its MEDCAC Wednesday as part of its ongoing national coverage analysis (NCA) of Provenge, which the agency initiated on June 30 – an action that triggered a 13.4 percent sell-off the next day of Dendreon's stock. (See BioWorld Today, July 2, 2010.)

CMS said the approval of Provenge in April as a treatment for asymptomatic or minimally symptomatic metastatic, castrate-resistant prostate cancer sparked informal inquiries for a national coverage determination (NCD) for such treatments.(See BioWorld Today, May 10, 2007, and April 30, 2010.)

Although some consider the price of $93,000 for Provenge high, the agency cannot consider cost effectiveness in its NCA.

Investors have had reason to worry about an NCD for Provenge, given the hit to Thousand Oaks, Calif.-based Amgen Inc.'s bottom line when CMS restricted payments for erythropoiesis-stimulating agents (ESA), including the company's Aranesp (darbepoetin alfa), in cancer and related neoplastic conditions. (See BioWorld Today, Aug. 1, 2007, and Sept. 26, 2007.)

The expected NCA completion date on Provenge is June 30, 2011, with a draft guidance memo from CMS anticipated by the end of March. But Wednesday's MEDCAC on Provenge ended up being much ado about nothing, said Roth Capital Partners analyst Joseph Pantginis.

While there were fears going into the meeting that CMS' use of a ranking system in its MEDCAC's voting process – which is very different from the up-or-down votes used by the FDA at its panel meetings – would lead to a level of ambiguity, "the voting appeared to certainly favor Provenge," especially for the most prominent questions on overall survival, Pantginis said.

The off-label use of Provenge at Wednesday's meeting, however, did not fare well. The MEDCAC gave Provenge scores of below 2 when it came to the committee's confidence about evidence to conclude that the immunotherapy improved overall survival and the avoidance of treatment burdens in patients whose prostate cancer has not metastasized, those who have metastatic castrate-resistant disease and symptoms more severe than minimally symptomatic or patients with metastatic prostate cancer, but who have not failed hormonal therapy.

But most analysts said they expected the lower confidence scores on the off-label questions, given the low expectations that Provenge would be used in those settings.

Provenge won a high mark of 4.1 in the committee's confidence about extrapolating overall survival and avoidance of treatment burdens in community-based settings. It also received an intermediate 2.9 grade about extrapolating the Provenge data in patients belonging to demographic groups that may have been underrepresented in Dendreon's trials – a score JP Morgan analyst Cory Kasimov called "promising." Such a score on that question, he added, could potentially have favorable implications when thinking about how European regulators are looking at the path forward for Provenge.

Although Kasimov acknowledged "this statement could be a bit of a reach." Nonetheless, he said he expected a "straightforward path," with no new major trials for Provenge. When it comes down to it, Kasimov said, Wednesday's MEDCAC was "all bark and no bite."

In a statement after the meeting, Dendreon CEO Mitchell Gold said the company would continue to work with CMS as it deliberates throughout the NCA process to "ensure patients with advanced prostate cancer have access to Provenge."

The outcome of Wednesday's MEDCAC was not only a win for Provenge, said Argos Therapeutics Inc. CEO Jeff Abbey, whose firm also is pursuing development of autologous cellular immunotherapies, but a "major milestone" for all biotechs in the space. Recently reported interim Phase II results showed that Argos' AGS-003 in combination with sunitinib had a median progression-free survival of 14.9 months for intermediate risk and six months for poor risk in patients with metastatic renal cell carcinoma (mRCC).

The company plans to meet with the FDA in January to discuss plans for a Phase III trial of AGS-003 as a first-line treatment in combination with sunitinib in mRCC, and currently is in discussions with investors and potential partners about financing the study, which is expected to start in the middle of next year, Abbey told BioWorld Today.

AGS-003 is part of Argos' Arcelis platform portfolio of personalized RNA-loaded dendritic cell immunotherapies for cancer and HIV and other infectious diseases.

As CMS goes forward in its deliberations about coverage decisions for autologous cellular immunotherapies, Abbey urged the agency to keep in mind that those products are very different than small-molecule drugs. "This is personalized medicine, and it takes a lot to do it, and it should be reimbursed at a reasonable level," he said. "It's just not the same as pills."