The oral shift reshaping psoriasis therapeutics

Psoriasis treatment has been transformed by injectable biologics targeting the IL-17 and IL-23 pathways, but the next competitive frontier is entirely oral. Patients with moderate-to-severe plaque psoriasis increasingly express preference for oral administration, and payers are attentive to any therapy that can deliver biologic-comparable efficacy without the cost and administration burden of subcutaneous injections. This preference dynamic is the commercial engine driving both icotrokinra and deucravacitinib.

The psoriasis oral therapy market has historically been served by small molecules such as apremilast (a PDE4 inhibitor), which offers modest efficacy relative to biologics. Deucravacitinib’s 2022 approval by the FDA as the first oral TYK2 inhibitor represented a meaningful step-change — clinical data showed superiority over apremilast on PASI 75 response rates. Icotrokinra now aims to go further, bringing the mechanistic precision of IL-23 pathway targeting — previously only achievable via injectable antibodies — into an oral dosage form.

This oral shift is not merely a convenience story. For dermatologists, oral agents expand treatment options in primary care settings where injectable administration is logistically challenging. For pharmaceutical companies, an oral product with biologic-level efficacy represents a substantial commercial opportunity — one that both Johnson & Johnson and Bristol-Myers Squibb are actively pursuing through distinct but overlapping mechanistic strategies.

Mechanistic differentiation: IL-23R antagonism vs. TYK2 inhibition

Icotrokinra and deucravacitinib both ultimately suppress IL-23 pathway signalling in psoriatic skin, but they do so at structurally and pharmacologically distinct points in the signalling cascade — a distinction with real consequences for selectivity, safety profiling, and label differentiation.

Deucravacitinib operates downstream of the receptor, binding allosterically to the regulatory pseudokinase domain (JH2) of TYK2 — the kinase that transduces signals from both IL-23 and IL-12 receptors, as well as type I interferon receptors. This allosteric mechanism, which locks TYK2 in an inactive conformation without occupying the active ATP-binding site, was designed to improve selectivity over earlier pan-JAK inhibitors. Critically, TYK2 inhibition blocks not just IL-23 but also IL-12 and type I interferon signalling, a broader immunological footprint than icotrokinra’s receptor-level blockade.

Icotrokinra’s selectivity argument is compelling: by acting at the IL-23 receptor specifically, it mirrors the pathway focus of the most efficacious injectable biologics (guselkumab, risankizumab, tildrakizumab) while delivering oral convenience. The macrocyclic peptide format — a structural class that occupies a chemical space between small molecules and biologics — is what makes this possible. Macrocycles can engage protein-protein interaction surfaces, such as the IL-23/IL-23R interface, that are typically undruggable for conventional small molecules. According to research published by Nature, macrocyclic peptides represent one of the most promising modalities for targeting extracellular receptor binding domains with oral agents.

“Icotrokinra’s macrocyclic peptide architecture allows it to engage the IL-23 receptor binding surface — a protein-protein interaction interface previously considered undruggable for oral agents — delivering the pathway selectivity of a biologic in a tablet.”

The selectivity difference carries implications for safety labelling. TYK2 inhibitors, by blocking a broader set of cytokine pathways, carry theoretical immunosuppression risks beyond the IL-23 axis. Deucravacitinib’s allosteric mechanism was specifically designed to minimise off-target JAK inhibition, and its approval label reflects a differentiated safety profile from pan-JAK inhibitors. Icotrokinra’s receptor-level, IL-23-specific blockade may yield an even narrower immunological footprint, which J&J will likely emphasise in its Phase III label strategy and physician communications.

Phase III positioning and clinical endpoint strategy

Icotrokinra is currently advancing through Phase III clinical trials for moderate-to-severe plaque psoriasis, with the programme evaluating efficacy on the standard dermatology endpoints of PASI 75, PASI 90, and Investigator’s Global Assessment (IGA). These are the same benchmarks against which injectable IL-23 inhibitors have set high bars — PASI 90 response rates above 70% for agents like risankizumab — making the Phase III readout for icotrokinra one of the most consequential data events in dermatology pipelines.

The clinical design choices J&J makes for icotrokinra’s Phase III will signal its commercial ambitions. A trial powered to demonstrate non-inferiority to an injectable IL-23 inhibitor (rather than only superiority to apremilast or placebo) would position icotrokinra as a genuine biologic replacement rather than a step-up from existing oral options. This framing matters enormously for payer negotiations and treatment guideline positioning, as bodies such as NICE in the UK and equivalent HTA agencies globally evaluate oral therapies against the full efficacy spectrum of available treatments.

Deucravacitinib’s approved label already establishes a strong clinical narrative: it demonstrated superiority over apremilast in head-to-head trials and a favourable safety profile compared to pan-JAK inhibitors. BMS has been building real-world evidence and expanding into psoriatic arthritis indications. For icotrokinra to displace deucravacitinib as the preferred oral option, J&J will need Phase III data that either demonstrates superior PASI scores or a meaningfully differentiated safety and tolerability profile — or both.

IP architecture and commercial strategy signals

The IP positioning of icotrokinra and deucravacitinib reflects their fundamentally different molecular classes — and this distinction shapes not only exclusivity timelines but also the competitive moats each company can build around its oral psoriasis franchise.

Icotrokinra’s patent estate is anchored in its macrocyclic peptide structure and the oral formulation technology required to achieve adequate bioavailability for a peptide-derived molecule. Macrocyclic peptides occupy a distinct IP space from both conventional small molecules and from biologic antibodies — they are neither subject to the biosimilar regulatory pathways that will eventually erode injectable IL-23 inhibitor revenues, nor are they directly comparable to the small-molecule kinase inhibitor IP families that govern deucravacitinib. This structural novelty provides J&J with a differentiated patent position that is difficult for competitors to design around without entering a new chemical class entirely.

Deucravacitinib’s IP is built around its allosteric TYK2 inhibition mechanism — specifically the pseudokinase domain binding mode that differentiates it from earlier ATP-competitive TYK2 inhibitors and from pan-JAK inhibitors. BMS has filed extensively around the deucravacitinib molecule, its crystalline forms, dosing regimens, and combination uses. The allosteric mechanism itself represents a defensible IP position, as the pseudokinase domain binding mode is structurally distinct from ATP-site inhibition. However, TYK2 as a target is now well-validated, and multiple companies including Pfizer (brepocitinib), Nimbus Therapeutics, and others are advancing TYK2 programmes that will eventually compete in the same space.

From a commercial strategy perspective, J&J’s positioning of icotrokinra as an “oral biologic equivalent” — targeting the same IL-23 pathway as its own injectable guselkumab (Tremfya) — is a deliberate portfolio management signal. Rather than cannibalising guselkumab sales, J&J appears to be building a tiered oral-to-injectable franchise: icotrokinra for patients preferring oral administration, guselkumab for those requiring or preferring injectable biologics. This dual-track strategy, analysed in detail through platforms such as PatSnap’s life sciences intelligence tools, mirrors approaches seen in other therapeutic areas where the same company holds both oral and injectable assets targeting the same pathway.

According to EMA regulatory frameworks, novel molecular entities in new chemical classes — such as macrocyclic peptide receptor antagonists — qualify for standard data exclusivity protections that provide market exclusivity independent of patent coverage, further reinforcing icotrokinra’s commercial protection upon potential approval.

Competitive outlook: who wins the oral biologic race?

The oral psoriasis competitive landscape in 2025 and beyond is a two-horse race between icotrokinra and deucravacitinib for the “oral biologic” positioning, with apremilast increasingly relegated to a lower-efficacy, cost-sensitive tier. The outcome will be determined by three converging factors: Phase III efficacy data, safety label differentiation, and payer access strategy.

Deucravacitinib’s first-mover advantage is substantial. With FDA approval since September 2022, BMS has had time to build physician familiarity, accumulate real-world evidence, negotiate formulary positions, and expand its label into psoriatic arthritis. First-mover advantages in dermatology are durable — apremilast maintained significant market share for years despite the availability of more efficacious biologics, largely because of established prescribing habits and payer tier positioning.

However, icotrokinra’s mechanistic argument is potentially decisive. If Phase III data demonstrate that an oral IL-23 receptor antagonist can achieve PASI 90 response rates approaching those of injectable biologics, the clinical narrative shifts fundamentally: icotrokinra would not be competing with deucravacitinib as a “better oral small molecule” but as an “oral biologic alternative” — a categorically different value proposition that could command both higher pricing and preferential guideline positioning. Research published through NEJM and other peer-reviewed dermatology journals has consistently shown that PASI 90 and PASI 100 responses are increasingly the benchmark patients and dermatologists use to define treatment success.

The competitive dynamics also extend to psoriatic arthritis, where both companies are pursuing label expansions. Deucravacitinib is in Phase III for psoriatic arthritis, and icotrokinra’s IL-23R mechanism is biologically plausible for joint disease given the role of IL-23 in enthesitis and axial inflammation. Whichever agent secures a broader label encompassing both skin and joint disease will gain a decisive advantage in the rheumatology-dermatology crossover prescriber population. Organisations such as WHO classify psoriatic arthritis as a significant comorbidity burden in psoriasis populations, reinforcing the strategic value of joint-indication coverage.

For drug discovery and IP professionals monitoring this space, the icotrokinra vs. deucravacitinib competition is a case study in how mechanistic differentiation, molecular class novelty, and clinical endpoint ambition interact to shape commercial outcomes. The patent landscapes, clinical trial designs, and payer strategy signals from both J&J and BMS are all visible in structured innovation intelligence platforms — making this one of the most data-rich competitive battles in current dermatology pipelines. Accessing and interpreting that data through tools like PatSnap’s life sciences platform is increasingly central to how pharma strategy teams make pipeline and BD decisions in this space.