Protagonist Therapeutics has announced positive topline results from Phase 3 clinical trials of icotrokinra, an investigational oral peptide drug for the treatment of moderate-to-severe plaque psoriasis. The ICONIC-LEAD study demonstrated that a daily oral dose of icotrokinra achieved significant skin clearance compared to placebo in adult and adolescent patients.
The study results indicate that 65% of patients treated with icotrokinra achieved an Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear skin) at week 16, compared to only 8% of patients in the placebo group. Furthermore, 50% of icotrokinra patients achieved a Psoriasis Area and Severity Index (PASI) 90 response (at least a 90% reduction in PASI score) at week 16, versus 4% in the placebo group. By week 24, 74% of patients had achieved clear skin and 65% achieved PASI90.
Psoriasis is a chronic autoimmune skin condition affecting approximately 2-3% of the world's population. In Australia, more than 500,000 people are affected each year. Plaque psoriasis, the most common form, is characterized by red, scaly patches that can cause itching and pain. Current treatments range from topical therapies to systemic injectable biologics. Icotrokinra aims to provide a more convenient oral alternative with comparable efficacy to injectable treatments.
Targeting IL-23 Receptor
Icotrokinra is a peptide drug that selectively blocks the interleukin-23 (IL-23) receptor. IL-23 is a key cytokine involved in the inflammatory pathways that drive psoriasis. By blocking this receptor, icotrokinra aims to reduce the overproduction of skin cells and the formation of psoriatic plaques.
Associate Professor Mark Smythe, founder of Protagonist Therapeutics, stated his vision was to find better therapeutics for diseases traditionally treated with injectable medications. He was inspired by venom-derived molecules for human therapeutics.
Financial Implications and Future Development
Protagonist Therapeutics is developing icotrokinra in collaboration with Johnson & Johnson. As a result of the successful Phase 3 completion, Protagonist will receive a $115 million milestone payment from Johnson & Johnson. The company has already earned $35 million for acceptance of an NDA in psoriasis and $15 million for starting a phase 3 study in a second indication, bringing the total milestone payments to $165 million.
"These positive phase 3 results confirm the compelling efficacy and safety trends that were observed with the previous Phase 2b FRONTIER-1 and -2 studies, highlighting icotrokinra's potential as a best-in-class oral agent providing an ideal combination of significant skin clearance with demonstrated tolerability in a once-daily pill for treating plaque psoriasis," said Dinesh Patel, President and CEO of Protagonist.
Comparison to Existing Therapies
While injectable biologics like infliximab and ustekinumab are effective for psoriasis, they are invasive and can be inconvenient for patients. Bristol Myers Squibb's Sotyktu (deucravacitinib), an oral tyrosine kinase 2 (TYK2) inhibitor, was approved in 2022 and is a competitor in the oral psoriasis market. Phase 3 trials are underway to compare icotrokinra head-to-head with deucravacitinib.
