Not surprisingly, Johnson & Johnson's Stelara has out-performed rival Enbrel in relieving moderate-to-severe psoriasis in a Phase III trial, but as a new drug, it may still need to prove its safety profile to win dermatologists over.

TNF-blocking Stelara (ustekinumab), from J&J's Centocor division and Medarex, targets the cytokines interleukin-12 and interleukin-23.

It has a PDUFA date at the end of this year after getting a great reception from the agency's Dermatologic and Ophthalmic Drugs Advisory Committee in June (¹ Also see "FDA Holds Up Centocor’s Ustekinumab Three Months But Wants No New Trials" - Pink Sheet, 8 August, 2008.).

If approved, Stelara would compete with two other TNF inhibitors, Enbrel (etanercept), the market leader from Amgen/Wyeth, and Abbot's newcomer Humira (adalimumab).

In the ACCEPT head-to-head study of about 900 patients presented at the European Academy of Dermatology and Venereology in Paris Sept. 18, researchers measured reduction in psoriasis after 12 weeks using the Psoriasis Area and Severity Index.

After two subcutaneous injections at weeks 0 and 4, 68 percent and 74 percent of patients taking ustekinumab 45 mg or ustekinumab 90 mg, respectively, achieved a PASI 75. This compares to 57 percent of patients undergoing Enbrel 50 mg subcutaneous injections twice weekly for 12 weeks who reached that score, the firm reported.

Ustekinumab also spurred higher marked improvements in secondary endpoints, and adverse event rates were similar for the three patient groups.

Expert dermatologists are unlikely to be surprised at the new data, as the results support previously reported findings, though the head-to-head study may have an impact with everyday dermatologists, said Joanna Kim, analyst at Decision Resources in Waltham, Mass.

"The trial has put to rest any questions - if anyone had them - that Stelara is more efficacious, but it did not answer the question of safety, which is the primary thing holding back immediate uptake," Kim said.

Warnings for TNF-inhibitors as a class have increased greatly recently and unlike Enbrel and Humira, approved first for related indications, Stelara's first indication will be psoriasis and may be viewed with more caution by prescribing doctors, Kim said.

The firm's summer-time survey of 150 dermatologists and primary care doctors showed that "a large percentage of dermatologists surveyed are aware of Centocor/Medarex's emerging interleukin (IL)-12/23 inhibitor Stelara and are willing to prescribe the drug upon its anticipated approval."

According to the report, "Both Stelara and Abbott's IL-12/23 inhibitor ABT-874 are generating excitement because of their high PASI 75 response rates and the potential for long-term remissions."

If all goes well for Stelara from the safety point of view in its first few years on the market, the drug will become competitive with others in the same class, Kim said.

As the first head-to-head trial of biologics in psoriasis, the ACCEPT study could also put Stelara in a better light with managed care organizations because it clearly shows better efficacy, Kim said.

Novel drugs sometimes get lower status with insurance companies, but these results could be used to place Stelara in the same tier as Enbrel, she added.

In the survey, 77 percent of dermatologists said Enbrel was their first-line biologic therapy.

"Thought leaders interviewed agree that no single biologic therapy has yet proven to be optimal for every type of psoriasis, but they believe that Enbrel offers the best balance of efficacy and safety," wrote analyst Madhuri Borde, in the Treatment Algorithm in Psoriasis report detailing the results.

"The critical factors driving the use of Enbrel ahead of other biologic therapies are its long-term safety data and physician familiarity with the drug," she wrote in the executive summary.

Humira was prescribed as a first-line therapy by 17 percent of dermatologists surveyed, and 44 percent said Humira was their most frequently prescribed second-line biologic agent.

Results indicate 38 percent of dermatologists surveyed are likely or very likely to increase their first-line use of Humira over the next two years.

- Emily Hayes (e.hayes@elsevier.com)

J&amp;J’s Stelara Beats Enbrel In Psoriasis

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J&J’s Stelara Beats Enbrel In Psoriasis