EPO Safety Review Will Be Closely Watched By Amgen, J&J And Roche

Roche will refine its development program for the continuous erythropoeisis receptor activator (CERA) R-744 based on an upcoming FDA advisory committee discussion of EPO safety issues, Worldwide Pharmaceuticals Head William Burns said.

"We need to get through that review, see if there is any refinement in the goal posts," Burns told investors during an analysts call April 21. CERA began Phase III trials during the first quarter.

FDA's Oncologic Drugs Advisory Committee will meet May 4 to discuss safety issues associated with the use of Amgen's Aranesp (darbepoetin) and Johnson & Johnson's Procrit (epoetin alfa). [Editor's Note: To ¹ watch a webcast or order a video/DVD of this meeting, visit FDAAdvisoryCommittee.com.]

During separate first quarter conference calls, Roche and Amgen opted to highlight different safety issues to be discussed at the meeting.

Roche said that the FDA advisory committee will discuss studies of Procrit conducted by J&J that show dose-dependent blood clot formation.

"What we've seen recently are some trials being run in the U.S. by competitors where they are increasing the dosage to try and sharpen the competitiveness of Procrit versus Aranesp," Burns explained.

"There are questions over some studies that J&J have had to stop due to blood clots," he continued. "Our read on it is it was to do with the dosage and how high they were pushing the dosage."

Amgen said that FDA convened the meeting based on European EPO studies showing reduced progression-free survival among cancer patients receiving EPO products.

"It really was called due to the two studies that were done on [J&J's] Eprex and [Roche's] NeoRecormon in Europe, where there was issue about long-term survival in cancer population," Amgen Exec VP-Global Commercial Operations George Morrow said during an April 22 analysts call.

"We at Amgen recognize there is an issue for epoetin alfa and beta. Just as a reminder, those products were used off-label at higher hematocrit levels than dictated by the label. We also feel there were some potential study design flaws," Morrow added.

"We decided to participate in that meeting because the focus was not on Aranesp," he explained. "There is no signal associated with Aranesp. We've had two prospective, randomized, placebo-controlled trials along these lines, and the safety for Aranesp has been comparable to placebo."

Scientists have speculated on a possible tumor proliferation mechanism associated with EPO (² (Also see "Amgen 2004 R&D Goals Focus On Oncology, Osteoporosis Products" - Pink Sheet, 29 Mar, 2004.), p. 33).

The European Union health regulatory authority is also reviewing the safety of EPO in the oncology setting, Roche noted.

Roche is confident that safety data will support erythropoietin use in approved indications. "We believe that the data is extremely good, that in formal, approved indications of EPO, this drug has a very profound, positive benefit to bring to patients," Burns said.

"What we have been doing to help with the authorities' review are looking at some of the big meta-analyses of the various studies we've run. There we can see that the use of EPO, if anything, is positive to the outcome in the clinical setting. I think that will be a good set of data that we share with the authorities."

Roche is conducting mortality studies on its EPO brand, but does not expect results before the FDA meeting. "There are one or two studies running mortality endpoints, but I don't believe they are due to report soon," Burns said.

Roche intends to market CERA in the U.S., assuming it prevails in patent litigation against Amgen (³ (Also see "Roche Will Challenge Amgen In U.S. EPO Market; Oncology Business Growing" - Pink Sheet, 4 Aug, 2003.), p. 23).

In Europe, Roche's anemia treatment NeoRecormon (epoetin beta) had a moderate quarter. While volume grew steadily, a price war was sparked by J&J's Eprex (epoetin alfa) in an attempt to regain share lost due to the incidence of pure red cell aplasia. NeoRecormon sales grew just 5% to $372.7 mil., Burns said.

J&J is also engaged in a pricing battle in the U.S. with Procrit against Aranesp (⁴ (Also see "J&J Draws Line On Procrit Price; Will Not Meet Amgen Aranesp 40% Discount" - Pink Sheet, 19 Apr, 2004.), p. 11).