One-year outcomes for icotrokinra (Icotyde, Johnson & Johnson), a targeted oral peptide that blocks the interleukin-23 (IL-23) receptor, showed durable skin clearance and symptom improvements in adults with moderate-to-severe plaque psoriasis.

These results follow previously reported significantly higher response rates than placebo and deucravacitinib through weeks 16 and 24 in the phase III ICONIC-ADVANCE 1 and 2 trials. Icotrokinra was approved in March by the FDA for the treatment of moderate-to-severe plaque psoriasis in adults and children aged 12 years or older.

In the studies, through 52 weeks, the authors concluded, “once-daily icotrokinra demonstrated robust, durable disease control in moderate-to-severe plaque psoriasis, with a high proportion of participants achieving completely clear skin and reporting symptom resolution and no psoriasis impact” on health-related quality-of-life (HRQOL). The results were published in the British Journal of Dermatology.

The ICONIC-ADVANCE trials randomly assigned 1505 adults to once-daily icotrokinra (200 mg), placebo for 16 weeks, or the active comparator deucravacitinib (6 mg) for 24 weeks, with all participants receiving icotrokinra thereafter.

Coprimary endpoints in both studies, assessed at week 16, were the proportion of participants achieving an Investigator Global Assessment (IGA) score of 0 or 1 (with ≥ 2-grade improvement from baseline), and a Psoriasis Area and Severity Index (PASI) score of 90 (≥ 90% improvement from baseline).

Previously reported results showed that treatment with icotrokinra resulted in significantly higher psoriasis-related response rates than treatment with placebo at week 16 and deucravacitinib at weeks 16 and 24, with adverse event (AE) rates similar to those achieved with placebo and lower than those with deucravacitinib.

Robust Long-Term Benefits

Pooling ADVANCE 1 and 2 data, the newly reported 52-week clinician-reported, patient-reported, and safety outcomes showed that 73% of participants randomly assigned to icotrokinra, 77% of those in the placebo/icotrokinra group and 78% of those in the deucravacitinib/icotrokinra group achieved IGA 0/1 at week 52.

Similarly, 71%, 72%, and 75%, respectively, achieved PASI 90 at this timepoint, with AE rates similar to those reported earlier.

Icotrokinra also provided “robust and durable” clearance of scalp psoriasis (76%-87% across groups) through week 52, the authors reported. “These rates are within the range of response rates observed for biologics targeting IL-23 and higher than those reported for other oral therapies,” they added.

Among secondary endpoints, clinically meaningful improvement in participant-reported itch using Psoriasis Symptoms and Signs Diary was sustained through week 52 and was reported by 74% of participants randomly assigned to icotrokinra, and 76% and 83% of the placebo/icotrokinra and deucravacitinib/icotrokinra groups respectively (pooled analyses).

There were no new safety signals through week 52.

In a related editorial, Dijon Millette, MD, of Broadgreen Hospital, University Hospitals of Liverpool Group, Liverpool, England, wrote that while icotrokinra “has the potential to be a game changer in the race for even more effective and convenient therapies for psoriasis,” intention-to-treat analysis “of early discontinuations and withdrawals from the study could provide a more informative analysis of efficacy and safety profile in real terms.”

He added that a head-to-head randomized comparative study between deucravacitinib and icotrokinra instead of placebo “would provide further granularity in assessing efficacy and safety within an ethically robust trial setting.”

Asked by Medscape Medical News to comment, Mohannad Abu-Hilal, MD, associate professor and head of the Dermatology Division at McMaster University in Hamilton, Ontario, Canada, described the findings as clinically meaningful. “This potentially gives us a new oral option with a level of efficacy that is quite impressive for an oral therapy, while maintaining the convenience of once-daily administration. This could be particularly attractive for patients who prefer not to use injections,” he said in an email.

However, Abu-Hilal, who was not involved with the study, emphasized that a head-to-head comparison against one of the highly effective injectable IL-23 inhibitors would be ideal, and that longer-term extension studies will be important for identifying uncommon or delayed safety events.

“There are also practical questions that these trials do not yet fully answer, and that hopefully will be addressed in future extension and sub-study analyses, such as what happens when treatment is interrupted or discontinued, how quickly disease returns after withdrawal, whether efficacy is recaptured after restarting therapy, and whether intermittent treatment affects longer-term disease control.”

The study was funded by Johnson & Johnson. Several of the study authors are employees of Johnson & Johnson, which funded the study, and the remaining authors are either advisory board members, consultants, speakers and/or investigators for and/or received honoraria and/or grants from the company. Millette declared having no conflicts of interest. Abu-Hilal disclosed being a speaker, advisor and/or receiving honoraria from AbbVie, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Galderma, Hikma Pharmaceuticals, Incyte, Janssen, Leo, L’Oréal, La Roche-Posay, Medexus, Novartis, Pfizer, Recordati, Sanofi Regeneron, and Sun Pharma.