ORLANDO -- Two-thirds of patients with moderate or severe plaque psoriasis had complete or nearly complete clearance at 4 months with an oral peptide targeting interleukin (IL)-23, a randomized study showed.
The primary analysis showed that 65% of patients treated with icotrokinra had an investigator global assessment (IGA) score of 0/1 as compared with 8% of patients assigned to placebo. Half of the patients had 90% skin clearance by the Psoriasis Area and Severity Index (PASI 90) versus 4% of the placebo group. Clearance occurred as early as 4 weeks, achieving statistical significant versus placebo at 16 weeks. IGA scores continued to improve out to 24 weeks in the icotrokinra arm, and PASI 90 results remained stable.
The improvement occurred with a safety profile similar to that of placebo, reported Robert Bissonnette, MD, PhD, of Innovaderm Research in Montreal, at the American Academy of Dermatology annual meeting.
"I've shown that icotrokinra demonstrated higher rates of clear/almost clear skin -- the scalp as well -- improved psoriasis symptom relief, there was a clear separation between placebo and active therapy as early as week 4, and the safety profile looked very good," said Bissonnette. "However, I'm only showing you data up until week 24, and it's only one session of numerous studies. More to come."
Patients assigned to active therapy received a fixed dose of icotrokinra. Andrew Blauvelt, MD, of Blauvelt Consultants in Annapolis, Maryland, wondered whether the results differed by patient body weight.
"The data are not out there yet," said Bissonnette. "I have seen weight data with patients lower than 90 [kg] versus more than 90, and I saw no major difference. As an investigator, I would like to see, and this will eventually be presented, results by weight categories, so 110 [kg], 120, and those at 130-plus, which is where we usually start to see issues with fixed-dose drugs."
Ian Landells, MD, of The Landells Clinic in St. John's, Newfoundland, asked about the availability of separate data on adolescent patients, as the study included adolescents and adults. Such data might provide insight into the question of whether earlier use of the drug might lead to better results.
"That has not been done yet, but it's a good question," said Bissonnette. "We are more and more interested in the field in terms of early indications, specifically in terms of preventing body progression over time."
Therapies targeting IL-23 have demonstrated good efficacy for moderate/severe plaque psoriasis and have become a treatment staple for such patients. However, IL 23-targeted therapies today are all injectables. Icotrokinra is a first-in-class oral peptide that selectively binds the IL-23 receptor to inhibit IL 23-pathway signaling, said Bissonnette.
In one phase II trial of the oral peptide, 16-week PASI 75 response rates were as high as 79% across a range of doses. In a long-term extension trial of a separate study, three-fourths of patients achieved PASI 75 at 52 weeks.
Bissonnette reported primary results from the randomized, placebo-controlled phase III ICONIC-LEAD trial of moderate/severe psoriasis. The study population comprised 618 adults and 66 adolescents (mean age 15 years), who were separately randomized 2:1 to once-daily icotrokinra or placebo and followed for 16 weeks, at which time investigators analyzed results from the co-primary endpoints of IGA 0/1 and PASI 90.
All patients initially randomized to placebo crossed over to the IL-23 inhibitor at 16 weeks. Adults randomized to icotrokinra were followed to 24 weeks, at which point those who met both co-primary endpoints were re-randomized to icotrokinra or cross over to placebo and continued follow-up to 52 weeks. Adults who did not meet both endpoints at 24 weeks continued the IL-23 inhibitor. Adolescents initially randomized to icotrokinra received active therapy throughout follow-up.
Baseline characteristics included a mean age of 42, psoriasis duration of 17 years, body surface area of about 25%, and PASI score of about 19. About 30% of patients had received prior phototherapy, 71-72% prior systemic therapy, and 32-37% prior biologic therapy.
The primary endpoint was the proportion of patients achieving IGA 0/1 and PASI 90 at 16 weeks. The analysis showed a 56.4% absolute difference in IGA 0/1 and 45.1% absolute difference in PASI 90, both favoring icotrokinra (P<0.001).
The 24-week results showed persistence or improvement in the icotrokinra group and rapid improvement in patients switched from placebo to the IL-23 inhibitor:IGA 0/1: 74% vs 63% on placeboPASI 90: 65% vs 41%, respectivelyPASI 75: 81% vs 70%
An analysis limited to patients who achieved the best results showed that 33% of patients in the icotrokinra group achieved IGA 0 by 16 weeks, increasing to 46% at 24 weeks. PASI 100 rates at the same time points were 27% and 40% among patients switched from placebo to icotrokinra. IGA 0 response rate increased from 1% at 16 weeks to 23% at 24 weeks, and PASI 100 response rate from <1% to 14%. Rates of scalp clearance at 16 weeks were 72% with icotrokinra and 15% with placebo, improving to 80% with icotrokinra at 24 weeks and 77% after cross over from placebo.
Significantly more patients had at least a 4-point improvement in itch score with icotrokinra at 16 weeks (58% vs 13%, P<0.001) and a Psoriasis Symptom and Sign Diary score of 0 (20% vs 1%).
Adverse event rates were similar in number and severity between treatment groups during the first 16 weeks.
Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. Follow
Disclosures
The study was supported by Johnson & Johnson (J&J). A co-author is a company employee.Bissonnette disclosed an extensive list of financial relationships, including J&J.Blauvelt disclosed multiple relationships with industry.Landells disclosed relationships with industry.
Primary Source
American Academy of Dermatology
Source Reference: Bissonnette R, et al "Icotrokinra, a targeted oral peptide that selectively blocks the interleukin-23 receptor, or the treatment of moderate-to-severe plaque psoriasis: results through week 24 of the phase III, randomized, double-blinded, placebo-controlled ICONIC-LEAD trial" AAD 2025;Late-Breaking Abstract Session I.
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