By Mary Welch
Two months after the temporary suspension of a U.S. Phase II/III trial of Scios Inc.'s Fiblast (trafermin) in acute stroke, the study was terminated based on a review of preliminary results by an independent data safety and monitoring committee.
Scios, of Mountain View, Calif., is developing Fiblast in collaboration with Wyeth-Ayerst Laboratories, the Radnor, Pa.,-based pharmaceutical arm of American Home Products Corp., of Madison, N.J.
Fiblast is a recombinant form of basic fibroblast growth factor (bFGF), a naturally occurring peptide with neuroprotective and angiogenic properties. It has been shown to protect neurons from the damaging effects of stroke, including oxygen and glucose deprivation.
Despite ending the U.S. study, a Phase II/III European trial will continue at the recommendation of the safety committee. Both trials had a planned enrollment of 900 patients, but only about 300 were evaluated in the U.S. So far, the number enrolled in Europe is "significantly less than the [U.S.] trials," said Mary Ann Allencourt, manager of investor relations for Scios.
The European trial started late last year. The U.S. study commenced in October 1997. How long it will take to complete European enrollment is unclear.
The safety committee's recommendation on the U.S. trial was based on an unfavorable risk-to-benefit ratio in the stroke patients treated with Fiblast vs. those treated with a placebo.
"The data from the U.S. trial is undergoing detailed analysis," Allencourt said. "There appears to be an excessive number of unfavorable outcomes in the Fiblast group, including possible increase in mortality, but no cause and effect relationship has been established. It's really premature to speculate any further."
In the U.S. trial, patients received, within six hours of suffering a stroke, infusions of either Fiblast or a placebo over eight hours. In the ongoing European trials, patients are treated within six hours of stroke onset, but the drug is infused over 24 hours.
Scios' stock (NASDAQ:SCIO) didn't take Wednesday's news hard. Shares closed at $8.625, down $0.187. The day after the temporary suspension in May, Scios' stock dropped nearly 14 percent. (See BioWorld Today, May 20, 1998, p. 1.)
"It appears to be an indication that the market had already taken the outcome into account based on the suspension," Allencourt said. "The end points are soft. It's a tough area, and it's widely appreciated that stroke trials are difficult."
Wyeth-Ayerst is running the trials, and has agreed to pay up to $12 million in cash and contribute another $32 million upon achievement of certain milestones as part of the deal to jointly develop and market Fiblast.
The two companies are waiting for data from Europe to determine whether to proceed with Fiblast again in this country, perhaps with a longer infusion period. There are no plans to initiate any new trials in U.S. because the European trial will serve to evaluate the longer infusion period. Future decisions will be based on that information, Allencourt said.
The decision also affects the two companies' strategy to test Fiblast for peripheral vascular disease (PVD) and coronary artery disease as well. Scios is leading the investigation for these vascular indications, and Phase II trials for both indications have been conducted.
Due to the stroke trial cessation, plans are a little behind projections, but the company still hopes to start another Phase II trial for PVD this year with a larger enrollment. No date for a follow-up Phase II trial for coronary artery disease has been set.
"Obviously our plans to continue in these areas may be delayed. We have to talk to the FDA, but we believe that the vascular trials will go forward," Allencourt said.
While the future of Fiblast is important to Scios and Wyeth-Ayerst, Scios' main focus is currently Natrecor (nesiritide), a hormone-based therapy for acute congestive heart failure.
Scios submitted a new drug application — the company's first — in April. In May, Scios signed a $60 million marketing deal for Natrecor with Bayer AG, of Leverkusen, Germany. (See BioWorld Today, May 27, 1998, p. 1.)
"Natrecor should be approved by the second quarter of 1999 if all goes as we expect," said Allencourt. "We believe Bayer's successful commercialization of Natrecor is the key factor to our success in the short term. We expect sales of Natrecor to take us to sustained profitability within two years." *