Immunex plans to submit 12-month, open-label Enbrel data in psoriatic arthritis patients following FDA's Jan. 16 approval of etanercept for the supplemental indication.

The sBLA approval was based on a 24-week, placebo-controlled study in 205 psoriatic arthritis patients, labeling states. Enbrel patients were administered 25 mg subcutaneously twice a week.

Clinical responses were seen after four weeks of therapy. "At 6 months, the ACR 20/50/70 responses were achieved by 50%, 37%, and 9%, respectively, of patients receiving Enbrel, compared to 13%, 4% and 1%, respectively, of patients receiving placebo," labeling says.

"Similar responses were seen in patients with each of the subtypes of psoriatic arthritis, although few patients were enrolled with the arthritis mutilans and ankylosing spondylitis-like subtypes," labeling states.

The number of tender joints decreased from 18 at baseline (on a 0-78 scale) to 5 after six months for Enbrel patients, compared to a decrease from 17 at baseline to 13 at six months for placebo. The number of swollen joints decreased from 13 to 5 (on a 0-76 scale) for Enbrel, versus 12.5 to 9.5 for placebo.

Psoriasis skin lesions also improved with Enbrel use compared to placebo. At six months, patients achieving an improvement of 50% or 75% in their psoriasis area and severity index scores were 47% and 23% in the Enbrel group versus 18% and 3% for the placebo arm.

The new indication is for "reducing the signs and symptoms of active arthritis in patients with psoriatic arthritis." The TNF inhibitor is already approved for rheumatoid arthritis and juvenile rheumatoid arthritis. Enbrel is co-promoted by Wyeth-Ayerst.

Enbrel is the first product approved for use in psoriatic arthritis. The biologic can be used as monotherapy or in conjunction with methotrexate, labeling says. Johnson & Johnson's anti-TNF agent Remicade (infliximab) is in Phase II for psoriatic arthritis; a 100-patient, placebo-controlled trial is underway in Europe and the U.S. J&J expects to initiate Phase III studies in 2003.

Psoriatic arthritis patients will be enrolled in Enbrel's access program until the biologic's manufacturing capacity is expanded. Immunex has estimated that its Rhode Island plant could produce additional shipments by October, but new Immunex owner Amgen is betting on a January 2003 start date (¹ Also see "Amgen Enbrel Projections Include 3-Month Cushion For Immunex Plant" - Pink Sheet, 24 December, 2001., p. 12).

Serious adverse events were seen in 5% of both Enbrel- and placebo-treated patients, labeling says. The only statistically significant difference was for injection site reactions (36% for Enbrel versus 9% for placebo), Immunex said. In both groups, 4% of patients withdrew due to adverse events.

Enbrel will be marketed by Immunex' first internal sales force of 100 reps. The reps will have two roles: to double-cover the higher-prescribing rheumatologists with Wyeth reps, and to detail the psoriatic arthritis indication to dermatologists (² Also see "Immunex Enbrel Building Sales Force For Psoriatic Arthritis Approval" - Pink Sheet, 27 August, 2001., p. 22).

The Jan. 16 approval also changes Enbrel labeling to allow for multiple administrations out of the same vial. Enbrel is supplied in 25 mg vials, and because the recommended starting dose for children is .4 mg/kg up to a maximum of 25 mg per dose, pediatric patients often do not use an entire vial per injection. Before the labeling change, patients were directed to dispose of any product remaining in the vial.

Labeling was also modified to lengthen Enbrel's shelf life. Upon reconstitution, Enbrel can now be stored for up to 14 days at 2-8 °C, compared to six hours under previous labeling.

Revised labeling also adds 24-month efficacy data in rheumatoid arthritis. Labeling previously cited only six- and 12-month data.

Enbrel is in Phase III in Wegener's granulomatosis and psoriasis, and in Phase II for ankylosing spondylitis. Phase II/III trials in congestive heart failure were discontinued in March 2001; Immunex is evaluating the data before deciding whether to proceed.

Immunex is also pursuing an Enbrel indication for delaying structural damage in psoriatic arthritis. Enbrel was approved for structural damage in rheumatoid arthritis patients in 2000. Immunex submitted the psoriatic arthritis sBLA on July 16, 2001 and received a six-month priority review.

Immunex Enbrel Psoriatic Arthritis 12-Month Data To Follow sBLA Approval

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