SILVER SPRING, Md. - A panel of experts advising the FDA recommended approval of Biogen Inc.'s psoriasis drug Amevive on Thursday.
While the FDA is not bound by the 8-to-2 vote cast by the Dermatologic and Ophthalmic Drugs Advisory Committee, the positive vote is certainly a step in the right direction for Biogen, of Cambridge, Mass., and also for the biotechnology industry, which has had a series of late-stage setbacks this year.
Under the best-case scenario, analysts have predicted that Biogen could launch Amevive (alefacept) sometime late this year or early next year. The annual U.S. market has been estimated at between $350 million and $500 million.
But Matt Geller, an analyst with CIBC World Markets in New York, told BioWorld Today that he wouldn't even venture to guess the estimated market for Amevive.
"There will be other products for this," he said. "Amevive has modest efficacy and you have to monitor the T cells. There have been no comparative studies, but it appears that Enbrel [being studied by Seattle-based Immunex Corp.] has better efficacy and is safer."
Some panelists saw it differently.
J. Richard Taylor, panelist and professor of dermatology at the University of Miami Medical School, Miami Veterans Hospital, said it looks like Amevive is "better than or at least equal to anything I've seen."
Echoing Taylor's views, Elizabeth Abel, a panelist and dermatologist in Mountain View, Calif., said, "We have to look at all aspects of Amevive, including improvements in quality of life and remissions. Anything on the market for this is a plus."
Amevive is designed to selectively target the CD45R0+ subset of T cells (memory-effector T cells), and Biogen wants to sell it as a treatment for patients with chronic plaque psoriasis who are candidates for phototherapy or systemic therapy.
While the panel and FDA reviewers raised concerns that Amevive could add to a reduction in a patient's T-cell counts, Biogen has long claimed that its product only affects a subset of T cells that cause disease.
The company presented the panel with data from two Phase III trials. The first was a 555-patient trial called Study 711, and the other was a 500-patient trial called Study 712.
According to the FDA's analysis, in Study 711, about half the participants experienced at least a single occurrence of a CD4 cell count below the lower limit of normal at some time during the treatment course (12-week dosing and 12-week follow-up). Comparatively, in Study 712, the figure was about 30 percent. Furthermore, the agency said 12 weeks following the last dose, about 20 percent of Study 711 patients had CD4 counts below normal.
Even though that may be the case, research notes released by Eric Schmidt, an analyst with SG Cowen Securities Corp. in New York, said, "Our consultants have long maintained that Amevive's safety profile is far superior to the standard of care (cyclosporine, methotrexate, steroids) and that dermatologists would not have contemplated developing biologics for psoriasis had it not been for the safety advantages offered by the targeted agents."
The FDA conceded that in clinical trials, there was no apparent relationship between lymphopenia and infections, and no opportunistic infections were observed.
The efficacy endpoint of the Phase III studies was achieving 75 percent or greater improvement in the Psoriasis Area and Severity Index (PASI). According to the FDA, by the PASI assessment 10 percent to 16 percent more alefacept-treated patients responded compared to placebo and 7 percent to 9 percent more alefacept-treated patients responded as measured by the Physician's Global Assessment rating.
"It shows efficacy; it may not be the barn-burner, but I come down on the side of it," said Lloyd King, a panelist and professor of medicine in the dermatology division at Vanderbilt University in Nashville, Tenn.
If Biogen launches this year, Amevive would be ahead of competition being posed by Xanelim, a humanized monoclonal antibody, being developed by Xoma Ltd., of Berkeley, Calif., and Genentech Inc., of South San Francisco.
Xanelim development was delayed in October when the FDA requested a pharmacokinetic study on news that the companies had made minor manufacturing modifications in the transition from small-scale production (clinical trials) to large scale. (See BioWorld Today, Oct. 8, 2001.)
Then in April, Xanelim was delayed again when Genentech announced that the pharmacokinetic study did not achieve the predefined statistical definition for comparability. (See BioWorld Today, April 8, 2002.)
So even though Xanelim is a few steps behind, some analysts, such as Elise Wang, of Salomon Smith Barney in New York, have told BioWorld Today that the products may not create major competition for each other since they impact patients in different ways. She said patients respond quickly to Xanelim, but once taken off the drug, they relapse or rebound quickly. Comparatively, it takes Amevive patients longer to respond, but if they do respond, there's a long-duration effect.
Meanwhile, Enbrel is the subject of a Phase II/III study in psoriasis patients. Company officials told BioWorld Today that Immunex intends to file its biologics license application sometime next year and anticipates a potential launch in 2004.
Hoffmann-La Roche Inc. has a once-daily oral drug on the market for psoriasis called Soriatane (acitretin).
According to the National Psoriasis Foundation in Portland, Ore., about 7 million people in the U.S. are affected by psoriasis, a non-contagious, chronic skin disease. The most common form is plaque psoriasis, which is characterized by inflamed patches of the skin topped with silvery white scales.
According to the foundation, only an estimated 1.5 million of the 7 million people suffering from the disease are being treated.
Biogen officials were not prepared to comment immediately after the panel meeting. Trading was held on Biogen shares Thursday.