Washington Editor

Amgen Inc.'s Enbrel could be the first TNF blocker to make it to market as a treatment for psoriasis, an inflammatory disease often mischaracterized as a disease of the skin.

Amgen, of Thousand Oaks, Calif., said Tuesday it filed a supplemental biologics license application for use of Enbrel (etanercept) in patients with moderate to severe plaque psoriasis. Rebecca Hamm, a spokeswoman for the company, would not speculate as to when Amgen and North American partner Wyeth Pharmaceuticals, of Madison, N.J., expect FDA action. Wyeth owns all rights outside North America.

Research notes provided by Leerink Swann & Co. in Boston said formal approval of Enbrel in psoriasis could occur by mid-2004.

Enbrel, developed by Wyeth and Immunex Corp., the Seattle-based company that merged with Amgen a year ago, was launched in 1998 as a treatment for rheumatoid arthritis (RA). Later it was approved for juvenile rheumatoid arthritis and psoriatic arthritis, and currently is being reviewed by the FDA as a treatment for ankylosing spondylitis. (See BioWorld Today, June 25, 2003; July 17, 2002; and Dec. 18, 2001.)

According to Amgen's figures, in 2002 Enbrel generated $802 million in revenues and the company's guidance for 2003 estimates the figure to reach $1.2 billion.

Enbrel works by binding TNF (tumor necrosis factor), one of the dominant inflammatory cytokines or regulatory proteins in both normal immune function and the cascade of reactions that causes the inflammatory process. According to Amgen's written material, the binding of Enbrel to TNF makes the bound TNF biologically inactive, resulting in a reduction in inflammatory activity.

Analysts told BioWorld Today Enbrel likely will outsell its competition in the psoriasis market. "For novel biologics, we think Enbrel has the best combination for efficacy, safety and patient convenience," Mike King, managing director with Banc of America Securities in New York, said.

And Bill Tanner, managing director with Leerink Swann & Co., told BioWorld Today Enbrel stacks up as the No. 1 drug. He believes the psoriasis indication could eventually generate $1 billion to $2 billion for Amgen and Wyeth. King, however, reserved comment on the revenue question, saying it could easily be worth $500 million or more, "but I'd rather wait and see how the psoriasis market develops."

Currently, he said about 8 percent of Enbrel prescriptions are being written by dermatologists off-label. "So if we're talking about $1.2 billion [Amgen's guidance on 2003 sales], that's over 100 million bucks off label, so if it's on label, it could easily double from there," he said.

Other TNF blockers under development in psoriasis are Remicade (infliximab), made by Centocor Inc., of Malvern, Pa., and Humira, Abbott Laboratories' product for RA.

Remicade is being studied in psoriasis, ulcerative colitis and spondyloarthropathies (such as ankylosing spondylitis), while Humira is expected to follow a course similar to the one taken by Enbrel, with applications down the road in juvenile RA, psoriatic arthritis, ankylosing spondylitis and psoriasis.

Outside the anti-TNF family, Enbrel faces competition from Amevive (alefacept), made by Cambridge, Mass.-based Biogen Inc., and Raptiva (efalizumab), from South San Francisco-based Genentech Inc. and XOMA Ltd., of Berkeley, Calif.

Amevive, designed to selectively target the CD45RO+ subset of T cells, was approved in the U.S. but rejected in Europe as a treatment for psoriasis. Regulatory officials apparently want additional clinical trials before they'll clear it in Europe, Tanner said. (See BioWorld Today, Feb. 21, 2003.)

Meanwhile, Raptiva, an adhesion molecule inhibitor (formerly called Xanelim), is expected to win FDA approval later this year as a treatment for moderate to severe psoriasis. (See BioWorld Today, May 13, 2002.)

Among other data, the sBLA for Enbrel includes a Phase III, double-blind, placebo-controlled, multicenter study of 583 patients who were randomized to receive Enbrel twice weekly at 50 mg or 25 mg, or placebo. The primary endpoint was the proportion of patients achieving a 75 percent or greater improvement in the Psoriasis Area and Severity Index (also called PASI 75) after 12 weeks of treatment.

According to Amgen, nearly half (49 percent) of the patients treated with 50 mg of Enbrel twice weekly and more than one-third (34 percent) of patients treated with 25 mg of Enbrel twice weekly achieved a PSAI 75 vs. 3 percent of patients receiving placebo.

Amgen said Enbrel is generally well tolerated, with injection-site reactions occurring more frequently than in the placebo group.

Amgen's stock (NASDAQ:AMGN) closed Tuesday at $69.99, up $1.08.