Washington Editor

The anemia drug epoetin alfa has been linked to 42 deaths in patients participating in a German clinical trial testing the drug's use as a therapy for acute ischemic stroke, Ortho Biotech Products LP reported.

However, a spokeswoman for the institute conducting the German study called release of the information premature and the result "of some sort of panic attack."

Ortho Biotech, the Bridgewater, N.J.-based Johnson & Johnson subsidiary, markets epoetin alfa in the U.S. as Procrit under a license from Thousand Oaks, Calif.-based Amgen Inc., which markets its own version of the drug as Epogen.

Epoetin alfa, which belongs to a class of drugs known as erythropoiesis-stimulating agents (ESAs), is a bioengineered form of a protein made in the kidneys that is critical to red-blood cell production.

ESAs are approved in the U.S. to treat anemia in patients with kidney disease and HIV and cancer patients with chemotherapy-induced anemia.

However, ESAs have come under scrutiny over the past two years because of reports of adverse cardiovascular events and cancer linked to the drugs. The FDA over the past year has updated the ESA product labeling four times, including the most recent warning that the drugs should not be used in patients undergoing chemotherapy intended to cure their cancer. (See BioWorld Today, Aug. 1, 2008.)

Ortho Biotech spokesman Mark Wolfe said investigators at the Max Planck Institute for Experimental Medicine in Munich, Germany, had been studying Eprex, the epoetin alfa version sold in Europe by J&J subsidiary Janssen-Cilag, as a therapy to treat stroke patients.

Preliminary results from the 512-patient study showed that 42 patients died in the treatment arm compared with 24 in the placebo arm, Wolfe told BioWorld Today.

Patients in the J&J-funded study, which began in 2003, were treated with Eprex within six hours of the onset of an acute ischemic stroke. While J&J provided the drug, Wolfe said, the company did not participate in designing or conducting the study. Wolfe directed all other questions about the study's design and outcomes to the German institute's Hannelore Ehrenreich.

However, Ehrenreich said in an email to BioWorld Today that "This mess was arranged by a person from J&J who prematurely in some sort of a panic attack and without my knowledge jumped to false conclusions and misinformed the FDA. The press release happened explicitly without my consent and against my will.

"In fact, we have very promising results regarding clinical outcome in ischemic stroke and may ultimately have a treatment that is less dangerous and more beneficial than thrombolysis. An increased death rate in the ITT population is restricted to patients who received systemic thrombolytic therapy with rtPA plus EPO." Ehrenreich said she has informed FDA officials of her concerns, and "I do hope that they will soon respond adequately."

She said a paper outlining the study is being submitted Monday and that she hopes it will clarify the situation. She did not say to whom the article is being submitted.

Earlier in the day Wolfe had told BioWorld Today that Ortho Biotech "chose to publicly communicate the preliminary results of the investigator-initiated study because of the potential safety implications for patients. We proactively communicated the results to the FDA and European regulators," he added.

A request this week by U.S. and Canadian regulators for a temporary halt of a Phase IIb stroke trial conducted by Stem Cell Therapeutics Corp. of its neuroregenerative therapy may be related to the German study, said CEO Alan Moore. SCT's Phase IIb REGENESIS stroke trial uses a regimen that includes epoetin alfa, Moore told BioWorld Today.

Health Canada and the FDA made the requests based on safety outcomes from an unidentified "foreign" stroke trial involving epoetin alfa, he said, noting that the agencies provided only limited information about the foreign trial to the Calgary, Alberta-based firm.

"We are assuming" that it is the German trial, "but it is not official," Moore said.

Health Canada also asked SCT to postpone enrolling patients in the firm's traumatic brain injury trial, which also plans to use the same drug regimen, known as NTx-265, until regulators have completed their analysis of the foreign study.

NTx-265, SCT's lead therapeutic product, is a regimen of human chorionic gonadotropin (HCG) and epoetin alfa.

NTx-265 is intended to stimulate the growth and differentiation of new neurons to replace the brain cells that were lost or damaged by a stroke and direct functional recovery of motor, visual and cognitive capacity after acute ischemic stroke.

Results of SCT's 15-patient Phase IIa BETAS stroke trial showed there were no serious adverse events related to NTx-265, Moore said, noting that 12 of those patients were in the U.S. and three were in Canada.

Patients in the BETAS study received dosages of HCG on the first, third and fifth day after a stroke. On the seventh, eighth and ninth day, the patients were administered dosages of epoetin alfa, he explained.

MRI scans after 90 days showed that NTx-265's neuroregenerative affect "filled the holes in the brain created by the stroke," Moore said. He noted that three BETAS study participants later died, but it was determined that none of the deaths were related to NTx-265. Moore noted that SCT's data safety monitoring board earlier this month had completed a safety analysis of REGENESIS and had recommended the trial continue per its designed protocol.

While SCT is disappointed that it had to temporarily halt its REGENESIS trial, Moore said, the firm "understands" and "supports" the safety concerns raised by drug regulators about the unrelated foreign trial.

SCT anticipates hearing from the FDA and Health Canada within the next two to four weeks, he said.

Analyst Michael Aberman, of Credit Suisse Securities LLC, said he viewed the German study as "highly irrelevant" to the ESA market, since the drug is not approved or used regularly in stroke patients. "Given the now well known safety concerns associated with ESA use, we do not believe there is a strong enough scientific rational to test ESAs in this indication," Aberman said in a research note.

Shares of SCT (CDNX:SSS) fell 8 cents Thursday, to close at 7 cents. Amgen's shares (NASDAQ:AMGN) closed at $59.99, down $1.74, while J&J's shares (NYSE:JNJ) were up $1.42, to close at $70.93.

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