Izokibep Potentially Clears Hidradenitis Suppurativa Lesions at 12 Weeks

Kim A. Papp, MD, PhD

Credit: LinkedIn

About 1 in 3 patients with hidradenitis suppurativa (HS) achieved complete abscess and inflammatory nodule clearance when treated with investigative drug izokibep over 12 weeks, according to new phase 2b/3 data.¹

In late-breaking research presented at the American Academy of Dermatology (AAD) 2023 Annual Meeting in New Orleans this weekend, a team of investigators reported that the novel small protein interleukin 17A (IL-17A) inhibitor was associated with possibly differentiated efficacy in treating HS, a chronic inflammatory skin condition currently with any drug approved by the US Food and Drug Administration (FDA).

The findings, presented by study author Kim A. Papp, MD, PhD, president of Probity Medical Research in Ontario, precede results from a double-blind, placebo controlled second part of the phase 2b/3 trial. The developing company Acelyrin also announced intentions to launch a phase 3 trial further assessing izokibep in patients with HS.

Papp and colleagues conducted the prospective, single-arm clinical trial to assess weekly 160 mg subcutaneous izokibep in patients with HS. They noted that the IL-17 pathway is a pathogenic driver for HS; izokibep has been observed in previous assessments to provide “high potency and potential for differentiated clinical response.”

In alignment with prior HS clinical trial standards, investigators recruited patients with lesions in ≥2 anatomic areas, ≥1 Hurley Stage II/III, and abscess/nodule (AN) counts of ≥3. Patients were further eligible if they previously had inadequate response, intolerance, or contraindication to oral antibiotics.

Investigators sought outcomes of Hidradenitis Suppurativa Clinical Response scores (HiSCR) of 50, 75, 90 and 100; they noted that placebo responses at ≥HiSCR75 are “historically minimal.”

The final assessment included 30 patients treated across 9 clinical sites. Mean patient age was 38 years old; 14 (46.7%) were Black and 21 (70%) were female. Mean HS duration was 12.8 years at baseline, and mean AN count was 9.7.

At 12 weeks of izokibep treatment, Papp and colleagues observed the following efficacy rates:

• 19 (65%) achieved HiSCR50
• 17 (57%) achieved HiSCR75
• 11 (38%) achieved HiSCR90
• 10 (33%) achieved HiSCR100

The most commonly reported adverse events (AEs) included mild to moderate injection site reaction. The team additionally observed 3 severe AEs in 2 subjects, including inflammatory bowel disease in a subject with pre-existing symptoms, and peri-colonic abscess/sepsis in the other subject. Relevant to pre-trial concerns, no patients reported candida infections.

Though investigators stated they are awaiting further results from the trial, the company’s response to initial outcomes were positive. In a statement accompanying the new data, Acelyrin found and chief executive officer Shao-Lee Lin, MD, PhD, stressed the industry’s continuous assessment for therapies that could provide resolution of HS.²

“We've long known that drug exposures in HS are lower compared to other inflammatory conditions and had hypothesized that the high potency of izokibep to IL-17A, as well as its small molecular size—about 1/10 the size of a monoclonal antibody—could generate deep levels of clinical response due to robust tissue penetration and potent target engagement,” Lin said. “We are delighted to see izokibep delivering high order HiSCR responses through 12 weeks and are pleased to see this hypothesis for izokibep unfolding now across 2 disease states, as shared today in HS and previously for psoriatic arthritis."

References

1. ^{Papp K, et al. Izokibep, a Novel IL-17A Inhibitor, Demonstrates HiSCR100 Responses in Moderate-to-Severe Hidradenitis Suppurativa: Open-Label Part A Results of a Phase 2b/3 Study. Paper presented at: American Academy of Dermatology 2023 Annual Meeting; March 17 – 21. New Orleans, LA. Accessed March 18, 2023.}
2. ^{ACELYRIN, INC. Announces Izokibep Achieves HiSCR100 Responses at 12 Weeks in Moderate-to-Severe Hidradenitis Suppurativa. News release. Acelyrin. March 18, 2023. https://acelyrin.com/press/izokibep-achieves-hiscr100-responses-12-weeks-moderate-severe-hidradenitis-suppurativa}