Dendreon Defends Provenge’s Stake Against Arrival Of Abiraterone

Dendreon Corp. is defending Provenge's position as the “foundation of care” for castration-resistant prostate cancer, following the recent approval of Johnson & Johnson’s Zytiga, and looking ahead to other novel drugs coming down the pike.

FDA approved oral, once-daily Zytiga (abiraterone) on April 28 for use with prednisone for metastatic CRPC, also called hormone-refractory prostate cancer, after treatment with docetaxel. Its price of $5,000 per month – with a median duration of treatment in trials of eight months – is arguably very competitive with Provenge’s $93,000 price (Also see "Zytiga Cleared Fast In Refractory CRPC, Can It Also Move To Earlier Use?" - Pink Sheet, 2 May, 2011.).

Dendreon CEO Mitch Gold: We are very interested in doing sequencing trials with new drugs as they are approved.

Many other drugs are in mid-to-late stage development, notably Medivation Inc./Astellas Pharma Inc.’s MDV3100 and Takeda Pharmaceutical Co. Ltd.’s TAK-700, both oral drugs with a similar mechanism of action as abiraterone (Also see "A Chock-Full Pipeline For Prostate Cancer Drugs" - Pink Sheet, 22 Nov, 2010.).

As a personalized therapeutic cancer vaccine, Provenge (sipuleucel-T) is more difficult to produce and currently access is limited, though the company has been working to bring manufacturing sites online and boost supply.

Facing The New Competition

During a May 2 investors call, Dendreon execs faced questions about how the company will handle competition from abiraterone.

In contrast with abiraterone, which is cleared for use in later-stage patients for use after chemotherapy, Provenge is approved for minimally symptomatic or asymptomatic patients, most of whom will not have had chemo. Abiraterone, however, is being tested in a Phase III trial in the pre-chemo population and results could become available by year-end.

“We’ve been having discussions with a lot of key opinion leaders in this space and even if the pre-chemo abiraterone trial were to be positive," Dendreon’s Chief Medical Officer Mark Frohlich said on the call, "overwhelmingly the feedback we’ve heard is even in that setting they would still view Provenge as the foundation of care and [as] being initiated first, followed at some later time by abiraterone.”

Dendreon argues that even if abiraterone is effective in first-line CRPC, Provenge will remain the “foundation of care.”

With so many new treatments set to become available, the Prostate Cancer Foundation is looking to get companies and clinicians together to devise sequencing trials to help determine the appropriate order of therapies.

Gold noted that the company is “very interested in doing sequencing studies of Provenge with other novel agents as they are approved.”

These studies would help determine, he explained, how long after treatment with Provenge clinicians should wait before they bring abiraterone on board, given that abiraterone must be used with prednisone.

Execs also were questioned about how Provenge’s high price would be received in “price-sensitive” Europe, where the company is planning to file later this year or early next year (Also see "Dendreon Expands Provenge To Europe" - Pink Sheet, 7 Jan, 2011.).

But the company is confident that the evidence supports use; Gold pointed out that the data clearly support use in patients with asymptomatic or minimally symptomatic disease. “[Provenge] has shown the largest reported survival benefit in this patient population and then patients have the option to go to other treatments downstream,” the exec said. “So we don’t see price as being the main issue here.”

The regulatory process in Europe is on track, COO Hans Bishop said, adding that ensuring European physicians become familiar with the product and have experience with it is “critically important.” The company is planning a worldwide trial in consultation with regulatory agencies to support the European application and is slated to treat the first European clinical trial patient with Provenge in the second half of this year.

In the U.S., a final national coverage decision is due from CMS on June 30 (Also see "Medicare Will Cover Provenge Labeled Uses, CMS Proposes; Off-Label Is Up To Contractors" - Pink Sheet, 30 Mar, 2011.). Many comments on the draft are urging CMS to clarify eligibility for treatment (Also see "Provenge Medicare NCD Needs More Clarity To Avoid Restrictions, CMS Told" - Pink Sheet, 9 May, 2011.).

An accompanying product-specific Q code expected July 1 will be a positive step toward greater reimbursement confidence for customers, execs argued, as it will allow electronic submission of claims and presumably accelerated payments.

Zytiga A Threat To Provenge

Company assurances aside, some analysts are still wary of the competition. The low price of Zytiga represents a threat if the pre-chemo data from the second Phase III study turn out to be compelling, Lazard Capital Markets analyst Joel Sendek said in a May 3 note.

A survey conducted by Lazard of 30 prostate cancer doctors showed that clinicians view Provenge as very costly and that the majority would prescribe abiraterone first if it became approved for use prior to chemo in metastatic HRPC.

“Physicians anticipate continuing patients on abiraterone long term until the emergence of symptoms or when PSA begins to increase, which would make those patients ineligible for Provenge, ultimately limiting the addressable patient population,” Sendek wrote.

So while management “maintains the view” that Provenge is the “foundation of care” in the pre-chemo setting, survey results suggest otherwise, he noted.

Similarly, Morgan Joseph TriArtisan analyst Shiv Kapoor cited competitive concerns in a May 3 note. He pointed out an additional advantage of abiraterone over Provenge, in that clinicians are able to monitor effects through changes in prostate-specific antigen levels. “We believe competition from abiraterone could be significant, given JNJ’s marketing muscle, lower price and PSA issues,” he wrote.

Launch Plans On Track

However, the company’s first quarter earnings call showed reasons to be positive: the launch of Provenge appears to be on track.

Dendreon reported revenue of $28 million in the first quarter, up from $21,000 the same time the previous year, and finished the quarter with $779 million in cash. The company reported signs of increasing demand for Provenge, with $15 million in sales for April, and said it was on target to reach $350 million to $400 million in revenue this year, about 50% of which will be earned in the second half.

As of the end of March, Dendreon reported that it had 135 prescribing sites for Provenge, out of the 225 it is targeting to get on board by the end of the second quarter.

The plan is to have three manufacturing facilities, one of which – in New Jersey – is up-and-running and is set to expand. The company has filed for approval for two other sites, in Orange County, Calif., and Atlanta. Both sites could be cleared by September.

The first quarter report provides encouraging signs that the company will reach its commercial plans for 2011, according to Leerink Swann analyst Howard Liang. The strong site activations suggest high demand for the product, in Liang’s view. “We believe the benefit observed with Provenge is real, that over time investors will be convinced of its benefits and that sentiment change could catalyze further stock appreciation,” he wrote in a May 3 note.

By Emily Hayes