Nomelcitinib tops Phase 3 endpoints in plaque psoriasis

By Daniel Okafor

In a 391-patient, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial in moderate-to-severe plaque psoriasis, InventisBio Co.’s nomelcitinib (D-2570) arms delivered PASI-90 rates above 70%, while PGA 0/1 response exceeded 80% at Week 16.

What did the registrational trial show?

Participants were assigned 1:1:1 to two nomelcitinib groups or placebo, putting about 130 people in each arm. The announcement gave no exact group totals, doses or country list for this multicenter study.

The trial used two response measures at Week 16:

• The primary endpoint was the percentage of patients achieving at least a 90% improvement from baseline in Psoriasis Area Severity Index score, known as PASI-90.
• The key secondary endpoint was the percentage achieving a Physician’s Global Assessment score of 0, meaning Clear, or 1, meaning Almost Clear, with a reduction of at least two points from baseline, known as PGA 0/1.

At Week 16, PASI-90 exceeded 70% in both nomelcitinib arms, with each significantly above placebo. The proportion reaching PGA 0/1 in the nomelcitinib groups exceeded 80%, also significantly above placebo. Other secondary efficacy analyses consistently favored nomelcitinib over placebo.

InventisBio said the study met its primary and key secondary endpoints. The release did not give numerical placebo responses, p-values, confidence intervals or treatment-effect estimates. That leaves the headline arm-level response rates visible, but not the full size of the benefit over placebo.

Takeaway: The Phase 3 result met both response endpoints at Week 16.

How quickly did it work, and what about safety?

Nomelcitinib is a Janus kinase homology 2 (JH2)-selective inhibitor of tyrosine kinase 2 (TYK2). More specifically, it acts on the JH2 pseudokinase regulatory domain of TYK2.

The separation from placebo appeared early. By Week 4, both treatment groups had significantly higher proportions of patients achieving PASI-90 and PGA 0/1 than the placebo group. The company reported further improvement as treatment continued through Week 16.

InventisBio described the safety profile as favorable and nomelcitinib as well tolerated. It identified no new safety signals. The company said those findings matched its earlier Phase 2 study and the experience with other JH2-selective TYK2 inhibitors.

The announcement offered no adverse-event counts, serious adverse-event rates, discontinuations, follow-up duration or event-level comparison with placebo. The safety conclusion therefore rests on the company’s qualitative summary rather than a detailed safety table.

Takeaway: The efficacy signal was present by Week 4, but the safety account still lacks event-level detail.

What comes next?

Another Phase 3 trial is underway as a head-to-head study with deucravacitinib (Sotyktu, BMS) serving as the active control. InventisBio expects that study to provide additional efficacy and safety data in moderate-to-severe plaque psoriasis.

The design shifts the comparison from nomelcitinib against placebo to nomelcitinib against deucravacitinib. If the head-to-head study reproduces the placebo-controlled result, direct response rates and safety findings should show how nomelcitinib compares with that branded active control.

In parallel, the company is running a US Phase 2 study in psoriasis and multiple Phase 2 studies in China for other indications. Those China programs include psoriatic arthritis, systemic lupus erythematosus, vitiligo and ulcerative colitis. They extend the clinical program beyond one skin disease without yet establishing efficacy in those conditions.

The announcement provided no regulatory filing or approval timeline. The next clearest evidence should come from the active-comparator trial and the continuing Phase 2 programs in psoriasis and other immune-mediated diseases.

Takeaway: Positive Phase 3 data establish the placebo-controlled result, while comparative performance and the regulatory path remain open.