Icotrokinra is a macrocyclic peptide that blocks the interleukin-23 receptor. Peptides of this kind normally have to be given subcutaneously or intravenously. This one is a tablet, swallowed once a day. In the phase 3 study ICONIC-LEAD, published by Bissonnette and colleagues in the New England Journal of Medicine in 2025, 65% of participants reached clear or almost clear skin at week 16, compared with 8% on placebo.
What icotrokinra is
The peptide, formerly known as JNJ-2113 and JNJ-77242113, was discovered jointly by scientists at Protagonist Therapeutics and Johnson & Johnson. Johnson & Johnson develops and commercialises it. Chemically it is a macrocyclic peptide, a short chain of amino acids whose backbone is closed into a ring.
Its target is the receptor for interleukin-23 (IL-23). IL-23 is a cytokine, a signalling protein that drives the inflammation behind plaque psoriasis. The peptide binds the receptor rather than the cytokine itself and so blocks the IL-23 pathway at the cell surface. The antibodies that act on the same pathway, such as guselkumab, risankizumab and tildrakizumab, are large proteins and are given subcutaneously. Icotrokinra is small enough to be formulated as a tablet. In its recommendation of July 2026 the CHMP, the expert committee of the European Medicines Agency, called it the first oral medicine that targets the IL-23 receptor. In ICONIC-LEAD it was given as one 200 mg tablet once a day.
ICONIC-LEAD: the phase 3 results in numbers
ICONIC-LEAD (NCT06095115) was a randomised, double-blind, placebo-controlled phase 3 trial. It enrolled 684 participants aged 12 and older with moderate to severe plaque psoriasis. 456 received the peptide and 228 received placebo. The two primary endpoints were read at week 16. The results published in the NEJM (Bissonnette R et al., 2025):
IGA 0/1, clear or almost clear skin: 65% with icotrokinra versus 8% with placebo
PASI 90, at least 90% improvement of the baseline score: 50% versus 4%
PASI 100, complete clearance: 27% versus under 1%
IGA 0, completely clear skin: 33% versus 1%
All four differences reached p < 0.001. From week 16 the placebo group was switched to the peptide. In the icotrokinra group the response continued to rise: according to the topline announcement by Johnson & Johnson of November 2024, 74.1% had reached IGA 0/1 and 64.9% PASI 90 at week 24. These week 24 figures are company data and are not in the NEJM abstract.
Adolescents made up a small part of the trial: 66 of the 684 participants were between 12 and 17. In this subgroup, presented at congress and reported by Dermatology Times, 84.1% reached IGA 0/1 at week 16 versus 27.3% with placebo, and 70.5% reached PASI 90 versus 13.6%. With 66 participants these percentages rest on small numbers and are not part of the NEJM paper.
Adverse events through week 16 were reported by 49% of participants in both groups. The most frequent were nasopharyngitis and upper respiratory tract infections. The authors state that longer and larger trials are needed to judge the balance of benefit and risk over time.
Why an oral IL-23 peptide is unusual
Most peptides cannot be swallowed as a medicine. Enzymes in the stomach and small intestine cut peptide bonds within minutes, and the intestinal wall lets through very little of a molecule this size and polarity. This is why nearly all peptide and protein drugs, from insulin to monoclonal antibodies, are given subcutaneously or intravenously.
Icotrokinra solves this through its molecular structure instead of a protective formulation. The macrocyclic ring makes the molecule more resistant to proteases and more rigid, so it keeps the shape that fits the receptor. Protagonist's platform designs such constrained peptides specifically for oral use. The amount that reaches the bloodstream after swallowing is still a small fraction, so the peptide has to bind its receptor very tightly and selectively for one tablet a day to be enough. Other oral peptides reach the bloodstream with the help of absorption enhancers in the tablet. This one relies on the molecule itself. ICONIC-LEAD is the first phase 3 evidence that this approach works clinically in a common inflammatory disease.
What the study does not answer
Long-term data. ICONIC-LEAD reports 16 and 24 weeks. The NEJM authors say that longer follow-up is needed. Johnson & Johnson reports no new safety signals through week 52 across the ICONIC programme, which is a company statement and not a peer-reviewed publication.
Comparison with other oral treatments. ICONIC-LEAD compared the peptide with placebo only. The two ICONIC-ADVANCE trials compared it with placebo and with deucravacitinib, an oral TYK2 inhibitor. According to Johnson & Johnson, both trials met all key secondary endpoints that measured superiority to deucravacitinib at weeks 16 and 24. The detailed numbers are company data.
Comparison with an antibody. ICONIC-ASCEND compares icotrokinra with placebo and with ustekinumab, an IL-12/23 antibody given subcutaneously. As of 27 October 2026 no results from this trial had been published (Johnson & Johnson, 18 March 2026).
Other indications. Trials in psoriatic arthritis, ulcerative colitis and Crohn's disease are ongoing. There is no approval in those indications.
Icotrokinra approval status in the US and EU
Verified on 27 October 2026. On 18 March 2026 Johnson & Johnson announced that the US Food and Drug Administration had approved the peptide under the brand name ICOTYDE, for moderate to severe plaque psoriasis in adults and in patients aged 12 and older with at least 40 kg who are candidates for systemic therapy or phototherapy (Johnson & Johnson press release). In the European Union the CHMP recommended approval on 23 July 2026, and the European Commission granted the marketing authorisation on 18 September 2026 (EMA, Icotyde). Pricing, reimbursement and the launch date are decided by each member state.
What this means for peptide research
For a long time the working assumption was that a peptide needs a needle. Among receptor antagonists, icotrokinra is the clearest counterexample so far: built from amino acids, swallowed once a day, with phase 3 results and two major approvals. Stability can now be designed into a peptide. Macrocyclisation, non-natural amino acids and backbone modifications have become standard tools for making a peptide survive the gut long enough to be absorbed. The trial also shows that a peptide can block a cytokine receptor in patients, which was previously the domain of antibodies and, more recently, of small molecules. Oral peptides are becoming a class of their own, with several more in late-stage trials in other therapeutic areas.
None of this changes anything about research-grade peptides in a laboratory. Icotrokinra is a prescription medicine and was approved as such.
Questions about icotrokinra
Is icotrokinra approved?
Yes. As of 27 October 2026 it is approved in the United States (FDA approval announced on 18 March 2026) and in the European Union (marketing authorisation of 18 September 2026) under the brand name ICOTYDE, for moderate to severe plaque psoriasis in adults and adolescents aged 12 and older with at least 40 kg. For other countries check the national regulator.
Is icotrokinra a biologic?
No. The biologics used against psoriasis are monoclonal antibodies, large proteins produced in cell cultures and given subcutaneously. Icotrokinra is a macrocyclic peptide of a much smaller size that is given as a tablet. The EMA describes it as the first oral medicine targeting the IL-23 receptor, as distinct from the antibodies against the same pathway, which are given subcutaneously.
How does icotrokinra differ from biologics against psoriasis?
Biologics such as guselkumab or risankizumab bind the IL-23 cytokine itself. The peptide binds the IL-23 receptor on the cell. Both block the same pathway, one as a subcutaneous antibody, the other as a tablet. ICONIC-LEAD did not compare the two directly. ICONIC-ASCEND, the trial against ustekinumab, had no published results as of 27 October 2026.
When will icotrokinra be available in the EU?
The EU marketing authorisation was granted on 18 September 2026. From which date it can be prescribed and reimbursed in a given country depends on national pricing and reimbursement decisions. Johnson & Johnson has not announced launch dates per country. Check the national authority or the manufacturer.
What do PASI 90 and PASI 100 mean?
PASI stands for Psoriasis Area and Severity Index, a score from 0 to 72 that combines redness, thickness, scaling and the affected body area. PASI 90 means the score fell by at least 90% from baseline, PASI 100 means complete clearance. IGA is the Investigator's Global Assessment on a scale from 0 (clear) to 4 (severe); IGA 0/1 means clear or almost clear.
Is icotrokinra available at Peptidebio?
No. It is a prescription medicine, not a research chemical. It is not part of our range and we do not sell it. This article is a research update on a published study.
Sources
Johnson & Johnson: ICONIC-LEAD topline results, 18 November 2024
Johnson & Johnson: ICONIC-ADVANCE 1 and 2 results, 8 March 2025
Johnson & Johnson: FDA approval of ICOTYDE (icotrokinra), 18 March 2026
European Medicines Agency: Icotyde, marketing authorisation 18 September 2026
This article summarises a published clinical study. It is not medical advice. Icotrokinra is a prescription medicine and not part of our range.