Protagonist Therapeutics achieves Phase 3 success with oral psoriasis drug

The phase 3 ICONIC-LEAD study has demonstrated that icotrokinra, a peptide drug designed to block the interleukin (IL)-23 receptor, significantly clears psoriatic plaques. This drug, developed in collaboration with Johnson & Johnson (J&J), will earn Protagonist a milestone payment of $115 million upon successful completion of the phase 3 study. Prior to this, Protagonist had already received $35 million for the acceptance of a New Drug Application (NDA) in psoriasis and $15 million for initiating a phase 3 study in a second indication, totaling $165 million in milestone payments.

The effectiveness of icotrokinra was measured using two scales: the Investigator's Global Assessment (IGA) and the Psoriasis Area and Severity Index (PASI). The IGA scale assesses psoriasis severity on a range from 0 to 4, with 0 representing clear skin and 4 indicating severe disease. Results from the study revealed that 65% of patients achieved clear skin (an IGA score of 0 or 1) by week 16, compared to just 8% in the placebo group.

The PASI score gauges the extent of psoriasis plaques on different parts of the body and also evaluates the severity of these plaques. A PASI score improvement of 90% or more (PASI90) signifies significant progress. In the study, 50% of patients treated with icotrokinra achieved PASI90 by week 16, in contrast to only 4% of the placebo group. The drug's benefits continued to grow over time, with 74% of patients achieving clear skin and 65% reaching PASI90 by week 24. Adverse events occurred in approximately 49% of both the treatment and placebo groups, indicating that icotrokinra did not increase the incidence of side effects.

Dinesh Patel, President and CEO of Protagonist, commented on these positive phase 3 results, noting they confirm the strong efficacy and safety trends observed in previous Phase 2b FRONTIER-1 and -2 studies. Patel emphasized icotrokinra's potential as a superior oral treatment for plaque psoriasis, offering a combination of significant skin clearance and tolerability in a once-daily pill. He also highlighted the success of Protagonist's innovative peptide technology platform in developing new chemical entities to address unmet needs in various disease areas.

Psoriasis, a common autoimmune skin disorder, affects about 2-3% of the global population. It occurs when the immune system triggers the overproduction of skin cells, leading to the formation of plaques. Plaque psoriasis, the most prevalent form, accounts for 85-90% of cases. While there is no cure for psoriasis, various treatments exist, ranging from topical applications to systemic drugs. Injectable monoclonal antibody therapies like infliximab and ustekinumab are among the most effective systemic treatments. However, icotrokinra aims to provide a similarly effective treatment through an oral route, reducing the invasiveness and complexity of the treatment process.

Bristol Myers Squibb's Sotyktu (deucravacitinib), a tyrosine kinase 2 (TYK2) inhibitor, is a popular oral psoriasis medication approved in 2022. Protagonist and J&J are positioning icotrokinra to compete in this market, and head-to-head phase 3 trials comparing the two drugs are currently underway.