CHICAGO — The future of psoriasis therapy lies in oral therapies now in development, Neil J. Korman, M.D., reported at the 11th International Psoriasis Symposium sponsored by the Skin Disease Education Foundation.
“Biologics have made an enormous difference in people's lives, but if you ask a patient if they want a shot or a pill, we all know the answer to that question,” Dr. Korman said.
The new drugs in development fall into two categories: drugs that target interleukin-12 and interleukin-23, and orally available small-molecule therapies.
In humans, IL-12 mRNA has been detected in psoriatic plaques but not in normal skin. Immunoreactivity for IL-12 is also increased in psoriatic plaques.
Investigators at Centocor have developed a fully human monoclonal IL-12 antibody, CNTO 1275, that demonstrated “a low placebo response and a very beautiful dose-response curve” in an ongoing phase II trial, said Dr. Korman of Case Western Reserve University, Cleveland.
A total of 252 patients were treated with a single dose of 50 mg or 100 mg, or a weekly dosage of 50 mg or 100 mg for 4 weeks. The primary end point of a 75% or greater improvement in the Psoriasis Area and Severity Index (PASI 75) at week 12 was achieved by 52%, 59%, 67%, and 81% of patients in the four treatment groups, respectively. In contrast, only 1.6% of the 67 placebo-treated patients achieved a PASI 75.
At week 20, there was no significant difference in safety data between any of the groups, he said.
Two phase II psoriasis studies are now underway to evaluate STA-5326, an orally available small molecule that inhibits production of IL-12 and IL-23. The molecule was discovered and is being developed by Synta Pharmaceuticals.
An oral formulation of pimecrolimus has been developed by Novartis and studied in 143 patients with moderate to severe chronic plaque psoriasis in a randomized, double-blind phase II trial.
At week 13, the median change in PASI scores from baseline was about 85% in patients treated with 30 mg twice daily for 12 weeks.
One safety finding is that patients reported a warm sensation when taking oral pimecrolimus and increased GI disorders, including diarrhea and nausea, which appear to be dose dependent, he said.
In the same category is ISA 247, a novel calcineurin inhibitor developed by Isotechnika, which is structurally similar to cyclosporine and is three times more potent than cyclosporine in vitro. In a phase II study, about 74% of patients given 0.75 mg/kg twice daily for 12 weeks achieved a PASI 75 response. The incidence of hypertension was lower than in previously reported trials of cyclosporine.
Early data from an ongoing phase III study in Canada showed that only 4.4% of 453 patients treated with ISA 247 had more than a 30% increase in creatinine. This compares very favorably with creatinine elevations reported with cyclosporine, suggesting that ISA 247 is safer than cyclosporine, he said.
Finally, Biogen Idec Inc. has developed BG-12, a more efficacious and tolerable oral formulation of fumaric acid esters that will be entering phase III trials in the United States. Fumaric acid esters have been used successfully for decades in Germany to treat psoriasis, but GI side effects have limited their use.
Dr. Korman has received funding from Centocor, Novartis, and Synta.
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