Oral psoriasis therapies: 54% PASI 100 and dosing differences

At week 48, 54% of patients with plaque psoriasis in the open-label ONWARD3 extension achieved PASI 100 with envudeucitinib, although the study had no placebo control.

Lebwohl called the finding a milestone for oral treatment: “For an oral therapy to achieve 54% PASI 100 ... is quite an accomplishment and something we have not seen before with a pill.”

He also noted that many biologics and oral therapies achieve higher degrees of PASI 100 over a year, so 54% does not establish superiority across treatment types.

In an August 10, 2026 news release, Alumis positioned the result as the highest reported PASI 100 skin clearance among oral therapies. That is the manufacturer’s claim; the ONWARD3 result came from an open-label extension without placebo control.

Mark Lebwohl, MD, a dermatologist, dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai and chairman emeritus of its dermatology department, reviewed these oral options in a recent Dermatology Times Expert Perspectives custom video series. He addressed dosing, safety, efficacy and responses at specific psoriasis sites.

Mechanism, safety and comparative efficacy

Zasocitinib, from Takeda, and envudeucitinib, from Alumis, are oral TYK2 inhibitors. Icotrokinra, marketed as Icotyde by Johnson & Johnson, is an oral IL-23 receptor antagonist. Neither TYK2 inhibitor has faced icotrokinra in a head-to-head trial, and the available efficacy data appear similar, according to Lebwohl.

Lebwohl said long-term safety and efficacy remain central concerns. He anchored expectations in years of experience with deucravacitinib, or Sotyktu, from Bristol Myers Squibb, another TYK2 inhibitor. He expects zasocitinib and envudeucitinib to benefit from that history and thinks clinicians will overwhelmingly regard both as safe, although that remains a prospective judgment rather than a head-to-head safety finding.

Lebwohl’s efficacy judgment was direct: “Certainly compared to apremilast, the new TYK2 inhibitors have been compared and they are much more effective.”

He expects a marketing war among the new agents, saying all three are more effective than apremilast and that he cannot identify a clear reason to use one over another. Without a TYK2-versus-icotrokinra head-to-head trial, comparative selection currently rests on indirect efficacy evidence, emerging safety experience and dosing schedules.

Response timing and dosing

Lebwohl said icotrokinra and the TYK2 inhibitors do not peak at 16 weeks. Patients continue to gain additional benefit through 24 weeks, with the peak effect arriving a little later. That pattern makes a 16-week snapshot an incomplete basis for comparing the agents.

The practical schedules differ:

• Envudeucitinib: taken twice a day.
• Zasocitinib: taken once a day, with or without food.
• Icotrokinra: normally taken in the morning on waking, followed by at least 30 minutes without food.

Where responses diverge

Scalp involvement is mostly uniform in psoriasis, and a high proportion of patients report it, Lebwohl said. Itching can be particularly severe in this group. Most patients respond to the same systemic drugs used for the rest of the body.

Response separates more clearly at the fingernails. Normalization requires the nail bed and nail matrix to recover, a process that usually takes months because clinicians treat the disease first and the nails then grow back in.

Palms and soles are the second site of divergence. Lebwohl said difficulty getting large biologic molecules through the thick stratum corneum via the small peripheral vessels of the hands and feet may explain their poorer response to biologics. Oral agents are much smaller, and he has seen good responses in palms and soles.

Reports have largely involved oral JAK inhibitors. Lebwohl expects some of the new drugs to benefit palm and sole psoriasis, which would give clinicians another choice because, in his assessment, all the agents appear safe and effective.

What does this change for clinicians?

The comparison gives clinicians three oral agents to weigh, but no head-to-head efficacy evidence identifies a winner. The practical choice will turn on dosing fit, the patient’s disease distribution and how much weight clinicians assign to emerging safety experience. What the evidence supports is a choice among these agents, not a declaration that one is best.

The 54% envudeucitinib result is the strongest concrete long-term signal in this comparison, but its uncontrolled design and sponsor-led interpretation keep it short of proof of superiority over biologics or other oral therapies.

Direct trials and longer follow-up should test whether the later-peaking response produces higher one-year PASI 100 rates and whether benefits persist across scalp, nails, palms and soles, giving prescribers a firmer basis for sequencing these therapies.