Novel nanobody izokibep demonstrates ‘high rates of response’ in psoriatic arthritis
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SAN DIEGO — Izokibep, a novel interleukin-17A inhibitor and nanobody drug, demonstrates “high rates of response” in psoriatic arthritis through 46 weeks, according to a speaker at ACR Convergence 2023.
“Izokibep [Acelyrin] is one of two nanobodies that are coming along,” Philip J. Mease, MD, of the Swedish Medical Center/Providence St. Joseph Health, and the University of Washington School of Medicine, told Healio. “It is a completely new approach to drug creation and manufacture.”
The difference with izokibep is a high IL-17A binding affinity (KD = 0.3 pM), small molecular size (18.6 kDa) and an albumin attachment site, according to Mease.
“The izokibep molecule is tiny compared to the other molecules of our biologic medications,” he said. “It has the same mechanism as a typical IL-17A inhibitor but delivered in a much smaller package.”
Previous week 16 data showed that 52% of patients achieved ACR50 response after treatment with izokibep, while 88% demonstrated enthesitis resolution. The current phase 2 data set includes results through 46 weeks for izokibep 80 mg and 40 mg twice a week.
“The study officially closed at week 16, but they decided they had enough information that it was going to be really good stuff,” Mease said. “If they were doing it over again, they would have finished out the week 46 data.”
The analysis included 44 patients assigned to 40 mg izokibep twice weekly, 47 assigned to the 80 mg twice-weekly dose, and 44 patients assigned to placebo who were switched to 80 mg twice-weekly at week 16. Baseline data showed patients had a mean age of 49 years (standard deviation, 12), a BMI of 29 (SD, 5), a PsA duration of 7 years (SD, 8), a swollen joint count of 10 (SD, 7) and a total joint count of 17 (SD, 10). Mean baseline DAPSA score was 47 (SD, 22), while the mean baseline PsAID-9 score was 5.9 (SD, 1.8), and the mean PASI score was 10 (SD, 6) in patients with a BSA greater than 3%.
In those with enthesitis, the mean Leeds enthesitis index (LEI) was 1.5 (SD, 0.5) and the mean SPARCC score was 3.4 (SD, 2.8). Prior TNF inhibition was reported in 13% of the cohort.
According to the researchers, 81% of patients in the izokibep 80 mg group achieved ACR50 response.
“That is higher than what you see for ACR20 response for most drugs,” Mease said.
Other week 46 results showed that 50% of patients in the izokibep 40 mg dose group achieved ACR50 response. In addition, 57% of patients reached MDA at week 46.
“The highest rates we see with other drugs are in the 45% to 50% range,” Mease said.
Meanwhile, the PASI100 rate was 71% and enthesitis resolution was 89% among patients in the izokibep 80 mg group, according to the researchers.
“We are seeing really high rates of response,” Mease said.
Safety data indicated the presence of candida infection, but Mease stressed that candida infections are “expected” with IL-17 inhibition.
“Typically, we see rates of 2% to 3%,” he said. “In this instance, there was a single case.”
Injection site reactions were reported in 14.5% of patients, while 12.2% reported injection site erythema. Nasopharyngitis occurred in 6.9%, and headache and back pain each occurred in 5.3% of patients.
“Overall, it was pretty well-tolerated,” Mease said.
Looking ahead, Mease said a dose of 160 mg may be included in the phase 3 program, alongside the 80 mg dose.
“Let’s get bolder,” he said.
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Mease PJ. Abstract 1688. Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego.
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