J&J, Protagonist's oral anti-IL-23 meets primary goals in key psoriasis trials

Johnson & Johnson and Protagonist Therapeutics have announced positive top-line results from two significant Phase III trials, ICONIC-LEAD and ICONIC-TOTAL. These studies evaluated the efficacy of icotrokinra (also known as JNJ-2113), an oral peptide that targets IL-23, in patients aged 12 and above suffering from moderate to severe plaque psoriasis.

The majority of patients with moderate to severe plaque psoriasis often do not receive advanced therapies despite being eligible. Liza O'Dowd, the immunodermatology disease area lead at J&J Innovative Medicine, emphasized the potential of icotrokinra to offer a once-daily oral treatment option, addressing the needs and preferences of those living with this condition.

The ICONIC-LEAD trial involved 684 participants who were given either icotrokinra or a placebo once daily. The primary outcomes measured were Psoriasis Area and Severity Index (PASI) 90 and Investigator's Global Assessment (IGA) 0/1 with a minimum two-grade improvement. At week 16, 64.7% of patients treated with icotrokinra achieved IGA scores of 0/1, indicating clear or almost clear skin, while 49.6% reached a PASI 90 response. In comparison, only 8.3% and 4.4% of placebo recipients achieved these respective outcomes. By week 24, efficacy had increased, with 74.1% of icotrokinra-treated patients achieving IGA scores of 0/1 and 64.9% reaching PASI 90.

The ICONIC-TOTAL study focused on 311 patients with psoriasis affecting specific areas such as the scalp, genitals, and hands/feet. This trial also met its primary goal, with patients showing an IGA score of 0 or 1 with at least a two-grade improvement at week 16. This highlights the potential of icotrokinra in treating challenging cases of psoriasis. Safety data from both studies were consistent with previous Phase II results, showing similar rates of adverse events between the icotrokinra and placebo groups.

Johnson & Johnson and Protagonist Therapeutics plan to present detailed findings at forthcoming medical conferences and are preparing to submit applications for regulatory approvals. As part of their 2020 research collaboration, Protagonist will receive $165 million in milestone payments in the first quarter of next year. This includes $115 million for completing a Phase III study, $35 million for NDA acceptance in psoriasis, and $15 million for initiating a Phase III study in another indication. Protagonist is also eligible for up to $630 million in future milestones and 6% to 10% royalties on global net sales.

Protagonist CEO Dinesh Patel stated that the latest results further validate the company’s innovative peptide technology platform and its effectiveness in creating highly differentiated new chemical entities. The collaborative ICONIC clinical program also includes ICONIC-ADVANCE 1 and 2, which will evaluate the safety and efficacy of icotrokinra in moderate to severe plaque psoriasis against both placebo and Bristol Myers Squibb's Sotyktu (deucravacitinib). Additionally, the ICONIC-PsA program will investigate icotrokinra for psoriatic arthritis beginning early next year. A Phase IIb ANTHEM study for ulcerative colitis is nearing its conclusion, with top-line results for ICONIC-ADVANCE 1 and 2 and ANTHEM expected in the first half of next year.

Johnson & Johnson’s current immunology portfolio includes the IL-23 blocker Tremfya (guselkumab) and Stelara (ustekinumab), a dual inhibitor of IL-23 and IL-12, both approved for various autoimmune conditions.