The oral treatment is also effective in adolescents, an age group with limited systemic treatment options.
Oral icotrokinra led to substantial skin clearance of plaque psoriasis without increased adverse events, results of a phase three trial have shown.
Symptoms were reduced as quickly as four weeks in, with 15% of the icotrokinra group achieving a 75% reduction from baseline on the Psoriasis Area and Severity Index (PASI) compared to only 2% of the placebo group.
After 16 weeks of treatment, half of the treatment group achieved a PASI 90 response compared to 4% of the placebo group, and nearly 30% and less than 1% achieved a PASI 100, respectively.
In the treatment group, the average area of skin affected by plaque psoriasis fell from a quarter of the body to around 6%. The placebo group experienced minor change, decreasing by about 4% over the same period. A third of the treatment group also achieved an Investigator’s Global Assessment (IGA) score of 0 compared to only 1% of the placebo group.
The double-blind ICONIC-LEAD study included nearly 700 participants aged 12 years and older. They were randomised 2:1 to receive a single 200mg icotrokinra daily, a targeted oral peptide that selectively binds the interleukin-23 (IL-23) receptor, or placebo for 16 weeks. After 16 weeks, the placebo group was transitioned to treatment through to 24 weeks.
After 24 weeks, an IGA score of 0 was achieved by nearly half of the cohort.
Assessment of the adolescent subgroup, which made up a tenth of the cohort, found that 70% of the treatment group achieved a PASI 90 response at 16 weeks, compared to 14% in the placebo group.
By week 24, this had increased to nearly 90%.
“It is expected that oral medicine which needs to be taken daily won’t be as effective as a large dose given subcutaneously every 12 weeks, but it was still excellent,” Conjoint Professor Dedee Murrell, director of dermatology at the St George Hospital, UNSW, told Dermatology Republic.
Professor Murrell said the treatment had the potential to be a great alternative for people with needle phobia.
All participants had moderate-to-severe plaque psoriasis, defined as a minimum of 10% total body-surface area affected, a PASI score of at least 12 and an IGA score of at least three.
They were diagnosed with plaque psoriasis at least 26 weeks before screening and were candidates for phototherapy or other systemic treatment.
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Enrolment ended in 2024 but the trial is ongoing, with a randomised withdrawal and retreatment period from week 24 to week 52 for adults with a treatment response.
After 52 weeks, an open-label treatment period will run until week 156, then a four-week safety follow-up from the final dose. It is being conducted across138 sites in Argentina, Australia, Canada, China, Germany, Hungary, Italy, Japan, Poland, South Korea, Spain, Taiwan, Turkey, the UK and the US. The majority of participants are male (65%) and white (72%). About half of each group experienced at least on adverse event in the 16 weeks, most commonly nasopharyngitis and upper respiratory tract infection.
Oral therapy offers clear advantages over injectable treatment, but most oral therapies for plaque psoriasis are less effective than biologics and are associated with adverse events. As a result, patients with moderate-to-severe disease typically require injectable biologics to achieve meaningful disease control.
For children, systemic options in Australia are even more limited than for adults and Professor Murrell said it’s common that teens aren’t fond of a needle.
Researchers concluded that the percentage of participants receiving icotrokinra who had clear skin at week 16 was within the range of percentages observed with FDA-approved injectable biologics targeting IL-23 for adults at week 12 or 16.
“It’s amazing to have a small molecule like a peptide that can specifically block a cytokine pathway without needing an antibody to be specific enough” Professor Murrell said.
