These new data highlight the efficacy of JNJ-77242113 as a potential oral therapy option for moderate-to-severe psoriasis patients.
Once and twice-daily oral administration of interleukin (IL)-23–receptor antagonist peptide JNJ-77242113 met its primary endpoint of achieving a Psoriasis Area and Severity Index (PASI) score reduction of at least 75% or greater among those with moderate-to-severe plaque psoriasis, according to new findings.1
These findings were the results of a study published in The New England Journal of Medicine, conducted with the aim of assessing the performance of JNJ-77242113 as an oral drug. The study’s investigators noted the value of effective oral treatment options, as apremilast is known to be only moderately-effective compared to biologics.2
This new research was led by Robert Bissonnette, MD, dermatologist and president of Innovaderm Research Inc. in Montréal.
“The science behind advanced treatments for immune-mediated inflammatory diseases like PsO has advanced over the last few decades and patients desire treatment options that combine standard of care efficacy, an acceptable safety profile and flexible routes of administration,” said Robert Bissonnette, MD, chief executive officer and medical director at Innovaderm Research, Montreal, Canada.3 “The Phase 2b FRONTIER 1 data, as reported in NEJM, are very encouraging for the ongoing clinical development program and offer a reason to look forward to the continued research of investigational JNJ-2113 as an oral therapy that may offer an attractive and convenient treatment option for patients.”
The study, known as the FRONTIER 1 trial, was led by Janssen Research and Development in collaboration with external medical experts. The research team looked into the efficacy of JNJ-77242113 versus placebo in adult individuals 18 years of age and older that had diagnoses of moderate-to-severe plaque psoriasis.
The trial design, data analysis, treatment administration, and manuscript formation involved the input and participation of the investigators. Individuals deemed to be eligible as subjects met specific criteria, including a diagnosis of psoriasis at minimum a half a year beforehand and suitability for phototherapy or systemic therapy.
Patients were excluded if they had non-plaque or drug-induced psoriasis, or had previously received certain biologic treatments. Enrollment occurred across 60 sites globally, with the trial being a phase 2, double-blind, randomized, placebo-controlled study.
The investigators randomized the participants to distinct doses of JNJ-77242113 or placebo for 16 total weeks, with the groups being given 25 mg once or twice-per-day, 50 mg once-per-day, 100 mg once, or 100 mg twice-per-day.
The research team determined their main endpoint to be a reduction of 75% or more in subjects’ PASI score from the point of baseline at the 16-week mark. After completion, the participants were given the option to take part in a long-term extension phase known as FRONTIER 2 or to be given their final safety follow-up.
Among their secondary endpoints, the team looked at Dermatology Life Quality Index (DLQI) and Psoriasis Symptoms and Signs Diary (PSSD) scores. The investigators also noted that concomitant treatments had been restricted during the trial period.
The research team ended up randomizing a total of 255 subjects, noting that there was a mean PASI score of 19.1 at the point of baseline. The team also found that the participants’ average duration of their psoriasis was shown to be 18.2 years, adding that 78% of those featured in all trial cohorts had had previous systemic therapy.
PASI 75 response rates at the 16-week mark were shown to be substantially higher in JNJ-77242113-treated groups. They reported rates of 37%, 51%, 58%, 65%, and 79% for 25-mg once-daily, 25-mg twice-daily, 50-mg once-daily, 100-mg once-daily, and 100-mg twice-daily groups versus 9% for placebo, respectively.
These results demonstrated a substantial dose–response relationship (P<0.001). The investigators did find that adverse events included coronavirus disease 2019 for 12% of those in the placebo group and 11% in each of the JNJ-77242113 groups.
Additionally, the team noted that nasopharyngitis (among 5% and 7%, respectively) was an adverse event reported by subjects. They did add, however, that there was not evidence of a dose-related adverse event increase among those treated with the drug, as incidence of was comparable between each of the JNJ-77242113 dose groups (52%) and the placebo (51%).
“In this phase 2 trial, JNJ-77242113…showed a dose–response relationship and greater efficacy than placebo, as measured by the PASI 75 response at week 16, in patients with moderate-to-severe plaque psoriasis,” they wrote. “Overall, there was no evidence of a relationship between the JNJ-77242113 dose and the incidence of adverse events.”