Psoriasis Drug Shows ‘Stunning’ Early Promise
JANE SALODOF MACNEIL (Southwest Bureau)
KAPALUA, HAWAII — A monoclonal antibody that targets interleukin 12 and interleukin 23 has produced phase II results that investigators are describing as far superior to anything seen before in psoriasis.
The investigational agent, which is called CNTO-1275, will now be tested in a phase III trial. “If this drug continues to track well, maybe by 2008 we are going to have a drug that will be highly effective with a very long-lived response and convenient administration,” Dr. Craig Leonardi said at the Winter Clinical Dermatology Conference, Hawaii.
“Safety still has to be proven, but to date this is clearly the most stunning drug I've worked with,” added Dr. Leonardi at the conference, sponsored by the Center for Bio-Medical Communication Inc. Dr. Leonardi, a board-certified dermatologist with a private practice in St. Louis, contributed 22 of 320 patients with moderate to severe psoriasis in the phase II trial.
Dr. Gerald G. Krueger, the principal investigator, confirmed the development in an interview at a subsequent clinical dermatology seminar sponsored by Medicis, where he spoke on psoriasis management. “I've never seen anything like it either,” said Dr. Krueger, a professor of dermatology at the University of Utah Health Sciences Center in Salt Lake City.
CNTO-1275 is being developed by Centocor Inc., which sponsored the study. In phase II, half the patients who received only one 50-mg injection achieved Psoriasis Area and Severity Index (PASI) 75 scores and a Physician Global Assessment (PGA) of clear or excellent in 12 weeks.
A dose-escalating effect was seen with 59% of patients achieving the PASI target and 53% the PGA goal among those who received a total of 100 mg. In the 200-mg cohort, the proportions went up to 67% and 72%, respectively.
In the group that received the highest dose, (400 mg given in four 100-mg injections during the first 4 weeks of the trial), 81% reached PASI 75 and 83% had a PGA of clear or excellent at 12 weeks. Only 1.3% of patients kept on placebo achieved PASI 75. None had a PGA of clear or excellent.
More than 95% of patients had used topical agents, and nearly half (45%) had tried UVB before entering in the trial. About a quarter had tried methotrexate and PUVA light, respectively. About 15% had used acitretin, and 12% cyclosporine before the study.
Although 79% of treated patients and 72% of untreated patients had adverse events on trial, very few were serious: 3.6% of all treated patients vs. 1.5% of those on placebo. The proportion of side effects was similar for the highest dose and placebo groups. Upper respiratory tract infections were the most common adverse event.
The investigators described response to treatment as prolonged. Dr. Krueger said results from a continuation study will be released at the American Academy of Dermatology annual meeting this month.
The 12-week phase III trial, listed in December but not yet open, has set a target enrollment of 750 subjects with severe plaque-type psoriasis. Patients in the active arms will receive 45 mg or 90 mg subcutaneously at baseline and at week 4, and every 12 weeks thereafter. Patients will be followed up to 264 weeks in a planned long-term extension of the study.
Dr. Leonardi said the study design raises an issue that he has been thinking hard about. CNTO 1275 is injected subcutaneously every 3 months. If it were injected twice a week, he would probably teach patients to inject themselves. With such a long interval, he says he wonders whether patients will be able to do it well.
As he usually sees psoriasis patients quarterly, he is thinking that he will inject them in his office during their follow-up visits. “I don't know how this will work out, but what a nice problem to have,” he said.
Dr. Leonardi and Dr. Krueger both disclosed consulting relationships with Centocor.
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