New generation biologic sets bar for efficacy, safety outcomes for psoriasis

March 1, 2008

PHOENIX 2 is a phase 3 study evaluating the efficacy and safety of ustekinumab (Centocor), a fully human interleukin-12/23p40 monoclonal antibody in patients with moderate to severe chronic plaque psoriasis.

Key Points

Buenos Aires, Argentina - Ustekinumab, a fully human interleukin-12/23p40 monoclonal antibody, has yielded impressive efficacy and safety results in a phase 3 study investigating it as an infrequently administered subcutaneous treatment for patients with moderate to severe chronic plaque psoriasis, according to investigators speaking at the 21st World Congress of Dermatology.

Craig Leonardi, M.D., and Kristian Reich, M.D., presented the data from the PHOENIX 2 trial and shared their perspectives on the study results and the potential of ustekinumab during a live press conference Webcast sponsored by Centocor, the company developing ustekinumab (formerly known as CNTO 1275).

The study randomized 1,230 patients 1:1:1 to treatment with ustekinumab 45 mg, ustekinumab 90 mg or placebo.

At week 12, when data were collected for the primary efficacy analysis, patients were randomized to continue treatment with ustekinumab 45 mg or 90 mg, beginning with two induction doses and then injections every 12 weeks.

Within four weeks of initiating ustekinumab, patients experienced significant and clinically meaningful improvements compared with the placebo-treated controls as measured by PASI scores and the Dermatology Life Quality Index.

PASI response

At the primary efficacy analysis at week 12, 67 percent of patients treated with ustekinumab 45 mg and 76 percent of patients in the 90 mg group achieved a PASI 75 response compared with only 4 percent of the controls.

Week 12 PASI 90 response rates in the placebo and ustekinumab 45 mg and 90 mg groups were 1 percent, 42 percent, and 51 percent, respectively.

During continued follow-up, further benefit was seen in the ustekinumab groups.

PASI 75 response rates peaked at week 20 at 70 percent in the lower dose group and 79 percent in patients treated with ustekinumab 90 mg.

The PASI 75 response rates remained at those levels at week 24 and showed only a slight drop at week 28 before patients received their fourth injection.

Patients who crossed over from placebo achieved outcomes mirroring those seen among patients treated initially with ustekinumab.

The ustekinumab injections were well-tolerated, with only a low incidence of mild injection site reactions reported. There was no evidence of any drug-related or dose-related safety issues.

'First-line drug'

"Ustekinumab represents a new class of biologics that interferes with both interleukin-12 (IL-12) and IL-23-mediated pathways by binding to their common p40 subunit, and the responses achieved in this trial validate that new approach for treating psoriasis.

"Working via a novel mechanism, ustekinumab also brings new hope to patients who are underserved by existing treatments," says Dr. Leonardi, associate clinical professor of dermatology, St. Louis University Medical School, St. Louis, and partner at Central Dermatology, St. Louis.

"With its minimal dosing requirements and its remarkable efficacy and safety, ustekinumab appears to have all of the characteristics of a first-line drug.

"Based on my personal experience as an investigator, I believe the impressive data from PHOENIX 2 even understate the impact of this treatment. We had quite few patients enrolled in this trial, and I am pleased to report that were some of the happiest I have ever treated with an investigational agent," Dr. Leonardi tells Dermatology Times.

"The list of new therapies for psoriasis has been growing, but there are still considerable unmet needs for treatment of psoriasis patients.

"In particular, patients want therapy that is convenient and can deliver safe and effective long-term disease control," says Dr. Reich, M.D., professor of dermatology, Georg-August University, Goettingen, Germany, and partner at the Dermatologikum, Hamburg, Germany.

"The efficacy results for ustekinumab place it in a champion league of psoriasis therapies, and its safety is unmatched by any biologic so far. Those features, together with its convenient administration regimen, suggest ustekinumab has definite, first-line potential," Dr. Reich says.

Tom Schaible, Ph.D., spoke on behalf of Centocor.