Significant Improvement in Psoriasis Seen With Oral Drug

ORLANDO, Fla. — Adults with moderate to severe plaque psoriasis taking the novel oral drug icotrokinra had significant improvement starting at week 16, with increased response rates continuing through week 24, according to an interim analysis of a phase 3 trial.

The analysis of the ICONIC-LEAD placebo-controlled study was presented in a late-breaker session at the American Academy of Dermatology (AAD) 2025 Annual Meeting.

“As early as week 4, there’s a clear separation between placebo and active drug,” said Robert Bissonnette, MD, executive chairman and founder of Innovaderm Research, Montreal, Quebec, Canada, who presented the results.

Overall, 456 adults and adolescents aged 12 years or older received icotrokinra — a novel oral peptide that specifically blocks the interleukin 23 receptor — 200 mg once daily, and 228 received placebo. Results for the 66 adolescents in the trial will be presented at an upcoming medical meeting, said Bissonnette.

Adult and adolescent participants had a mean of 25%-27% body surface area covered with plaques. Baseline characteristics between those given icotrokinra vs placebo were similar: 30% of those on icotrokinra and 29% on placebo had prior phototherapy, 72% of those on icotrokinra and 71% on placebo had prior systemic therapy, and 32% of those on icotrokinra and 37% on placebo had prior biologic therapy. The mean Psoriasis Area and Severity Index (PASI) score was 20.

At week 16, 65% of adults who took icotrokinra achieved an Investigator’s Global Assessment (IGA) 0/1 (clear or almost clear skin), and half achieved a PASI 90 response compared with 8% and 4%, respectively, for those receiving placebo. The P value for both of those co-primary endpoints was < .001.

At 24 weeks, 74% of patients taking icotrokinra had IGA 0/1 and 65% achieved PASI 90. Of those patients, 46% reached IGA 0 and 40% reached PASI 100.

The IGA 0 and PASI 100 endpoints “are a little more stringent, the ones that we really want to achieve and what our patients really want,” said Bissonnette.

At week 24, 73% of patients reported a 4-point or more improvement in PSSD (Psoriasis Symptoms and Signs Diary) itch, and 38% had a PSSD symptom score of 0.

Adverse event rates were similar for icotrokinra and placebo, with nasopharyngitis and upper respiratory tract infection most commonly reported. About a quarter of patients in each group had an infection. No new safety signals were identified, said Bissonnette.

“These study results are promising and show the potential for treatment with icotrokinra to offer patients the unique combination of complete skin clearance and a favorable safety profile in a once-daily pill,” said Bissonnette in a Johnson & Johnson press release.

When asked to comment, Lawrence J. Green, MD, clinical professor of dermatology, George Washington University School of Medicine, Washington, DC, said the results “show efficacy similar to or even better than those of phase 3 trials of many biologics given subcutaneously.”

Green, who investigated icotrokinra in a phase 2 trial, told Medscape Medical News that the drug “is the first of a new generation of oral medications that will work similarly to current subcutaneous biologics.” He expects that patients will soon be able to choose “between a daily pill or a monthly or less frequent subcutaneous injection to control their psoriasis.”

“I am excited to see which way most patients prefer,” said Green.

Ahuva Cices, MD, assistant professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York City, called the data “impressive.” Cices told Medscape Medical News that additional data will be needed to validate safety and efficacy in hard-to-treat areas such as the scalp, inverse, genital, and palmoplantar areas, as well as nail psoriasis.

But she said that she was excited about icotrokinra. “This novel therapy has the potential to transform the way we treat psoriasis by providing a needle-free treatment option with the efficacy of injectables,” she said, adding that it might be used as a first-line therapy.

Johnson & Johnson said it will soon begin a head-to-head study of icotrokinra against the injectable biologic ustekinumab in phase 3 of ICONIC-ASCEND.

Cices said she’s also looking forward to that trial. “No other oral medication has been able to achieve results that rival that of our injectable medications,” Cices said.

The study was funded by Janssen Research & Development. Bissonnette is a paid consultant for Johnson & Johnson and disclosed that he is an advisory board member, consultant, speaker, and/or investigator, and received honoraria or grants from AbbVie, Alumis, Amgen, Arcutis, Bausch Health, Boston Pharma, BMS/Celgene, Dermavant, Eli Lilly and Company, LEO Pharma, Nimbus, Novartis, Pfizer, Regeneron, UCB, Ventyx Biosciences, Vyne, Xencor, and Zai Lab. Green reported that he is an investigator, speaker, or advisor for Investigator and speaker or advisor for Amgen, Alumis, Arcutis, BMS, Dermavant, Janssen Pharmaceuticals, Eli Lilly and Company, UCB, and Vyne. Cices had no relevant disclosures but reported that she is on advisory boards for Almirall, Amgen, Bristol Myers Squibb, Castle, Janssen Pharmaceuticals, LEO Pharma, and Regeneron; a consultant for Botanix and FRÉ Skincare; and a speaker for Sanofi.

Alicia Ault is a Saint Petersburg, Florida-based freelance journalist whose work has appeared in many health and science publications, including Smithsonian.com. You can find her on X @aliciaault and on Bluesky @aliciaault.bsky.social.