A new IL-23 inhibitor shows similar efficacy to that seen with injectable biologics currently approved for psoriasis.
Patients with plaque psoriasis have had significant improvement in their disease severity and extent after taking an oral interleukin-23 inhibitor, according to new research.
Almost 80% of patients who took the highest dose of the oral interleukin-23–receptor antagonist peptide JNJ-77242113 achieved a PASI response of 75% after 16 weeks, according to research in NEJM.
The researchers said that while there were several approved biologics that targeted the interleukin-23 pathway, one of their limitations was that they needed to be given intravenously or subcutaneously.
“Many patients prefer oral treatments over injections, and injections are especially problematic among children and among patients with a fear of needles,” they wrote.
“There is a need for efficacious targeted therapies that can be administered orally.
“Owing to its potency and stability in the gastrointestinal tract, this peptide is able to provide systemic interleukin-23 pathway blockade through oral administration.”
Participants in the phase 2 trial had moderate-to-severe plaque psoriasis, had had psoriasis for an average of 18 years, and had a mean PASI score at baseline of 19.
Almost 80% of participants had previously tried systemic treatments, the researchers said.
The 255 participants were randomly assigned to receive JNJ-77242113 at a dose of 25mg once daily, 25mg twice daily, 50mg once daily, 100mg once daily, 100mg twice daily or placebo for 16 weeks.
The researchers said there was a significant dose-response relationship.
At week 16, the percentages of patients with a PASI 75 response were 37% in the 25mg once-daily group, 51% in the 25mg twice-daily group, 58% in the 50mg once-daily group, 65% in the 100mg once-daily group, and 79% in 100mg twice-daily group. Only 9% of patients in the placebo group had a PASI 75 response.
“The level of reduction of psoriasis that was observed with higher doses of JNJ-77242113 at week 16 was similar in magnitude to the responses seen with several of the injectable biologics that are currently approved for psoriasis,” wrote the authors.
The drug blocks interleukin-23 signalling and the production of downstream cytokines such as interleukin-17, the researchers said.
The most common adverse events among participants were covid (12% of participants in the placebo group and 11% of those across the JNJ-77242113 groups) and nasopharyngitis (5% and 7% respectively).
At week 16, the percentages of patients who had adverse events was similar in the combined JNJ-77242113 group (52%) and the placebo group (51%).
The researchers said there was no relationship between increasing doses of the drug and the incidence of adverse events.
There were no deaths, major adverse cardiovascular events or cancers during the trial, they added.
More patients in the combined JNJ-77242113 group had diarrhoea compared with those in the placebo group, the researchers said.
“But the incidence among patients who received the highest doses was similar to the incidence among those who received placebo; this observation may reflect the variation that can occur with a small sample size.”
However, the researchers acknowledged that the number of participants was small and treatment duration was short, and said larger trials were needed.
In an accompanying editorial, professor of dermatology and epidemiology Professor Joel Gelfand noted that two infections (covid and an infected cyst) and a suicide attempt were reported as serious adverse events.
“Larger trials will be needed to determine whether such events are attributable to chance, psoriasis itself, or inhibition of interleukin-23 signalling,” he said.
“Furthermore, JNJ-77242113 needs to be taken on an empty stomach, and therefore, effectiveness may be lower in real-world settings.
Professor Gelfand, from the University of Pennsylvania Perelman School of Medicine, said the response may also be diminished by obesity.
“In the highest dose group, 100% of the patients with a body-mass index … of less than 25 had a PASI 75 response as compared with 68% of those with a BMI of 30 or higher.”
Professor Gelfand said the oral bioavailability of the medication was thanks to advances in bioengineering which made it possible for complex proteins to penetrate gastrointestinal proteases, mucus and cellular barriers.
