Phase 3 win for Protagonist Therapeutics with oral plaque psoriasis drug

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The promising trial results put icotrokinra on track to fulfill its potential as a best in class oral therapeutic for the chronic skin condition.

The phase 3 ICONIC-LEAD study showed that icotrokinra, a peptide drug that blocks the interleukin (IL)-23 receptor, was able to induce significant clearance of psoriatic plaques.

The drug is being developed in conjunction with Johnson & Johnson and Protagonist will earn $115 million as a milestone payment from the big pharma for successful completing a phase 3 study.

Protagonist has already earned $35 million due to acceptance of an NDA in psoriasis and $15 million for starting a phase 3 study in a second indication bringing its total milestone payments up to $165 million.

The IGA scale is used to measure severity of psoriasis and ranges from 0 to 4, where 0 is clear skin and 4 indicates severe disease. The results from the trial show 65% of patients were able to achieve clear skin (an IGA score of 0 or 1) at week 16 versus only 8% of the placebo group.

The PASI score relates to the amount of surface area on each part of the body that is covered by psoriasis plaques and also grades severity of the plaques. A score of 90 or more means that this has improved by 90% from the start of the study, which 50% of icotrokinra patients achieved versus only 4% of the placebo group.

The effects of the drug improved with time and by week 24, 74% of patients had achieved clear skin and 65% achieved PASI90. Around 49% of people in the treatment and placebo group had some form of adverse event, showing no increase with icotrokinra treatment.

"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.

"These results also continue to validate Protagonist's innovative peptide technology platform and its effectiveness in creating highly differentiated new chemical entities to address unmet needs in various disease areas."

New options for a common skin disorder

Psoriasis impacts around 2-3% of the world’s population. It is an autoimmune skin condition where the body produces too many skin cells following a triggering event that causes the immune system to start this overproduction.

In people with psoriasis, immune cells secrete inflammatory biomarkers that cause the skin to overproduce keratinocytes and create plaques on the skin that are characteristic of plaque psoriasis, which accounts for 85-90% of people with the skin condition.

There is no cure for psoriasis, but many treatments are available ranging from topical to systemic. The most effective of the systemic drugs tend to be injectable, such as the monoclonal antibody therapies infliximab or ustekinumab. Icotrokinra is aiming to be as effective as the injectable therapies but taking the oral route to reduce invasiveness and make the treatment easier for patients.

Bristol Myers Squibb has a popular oral psoriasis medication Sotyktu (deucravacitinib), a tyrosine kinase 2 (TYK2) inhibitor, which was approved in 2022. Protagonist and J&J are hoping to compete for some of this market and phase 3 trials testing the two drugs head-to-head are in progress.