Promising Trial Results Advance Lutikizumab to Phase III Study in Moderate to Severe Hidradenitis Suppurativa

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The results of a Phase II trial show that AbbVie’s lutikizumab (ABT-981) 300 mg every other week or 300 mg weekly produced higher response rates in adult patients with moderate to severe hidradenitis suppurativa (HS) who previously failed anti-tumor necrosis factor (TNF) therapy. The trial data show that those administered lutikizumab achieved higher response rates at 59.5% for those administered 300 mg every other week (nominal p=0.027) and 48.7% (nominal p=0.197) in the 300 mg weekly cohort compared with 35% with placebo, which was the trial’s primary endpoint for achieving HS Clinical Response (HiSCR 50) at week 16.

AbbVie said it will advance the clinical program for the investigational, dual-variable-domain interleukin (IL) 1α/1β antagonist to Phase III for the treatment of HS.

"AbbVie continues to pioneer research in the pursuit of new treatment options for patients with hidradenitis suppurativa, a frequently overlooked, underserved, and often suffering patient population," Roopal Thakkar, MD, senior vice president, chief medical officer, global therapeutics, AbbVie, said in a press release. "These results help us further understand the use of lutikizumab in adults with moderate to severe hidradenitis suppurativa, and we will continue to apply our more than 25 years of expertise in immune-mediated diseases in advancing our clinical program for lutikizumab in HS to Phase III."

Lutikizumab was evaluated in a 16-week, randomized, double-blind, parallel group, placebo controlled, dose-ranging, multicenter study to analyze the drug’s safety and efficacy in 153 adults with moderate to severe HS who previously failed anti-TNF therapy. Among those enrolled, 70.6% had severe baseline Hurley Stage 3 disease, which is the most extensive form of the condition and is characterized by scarring, lesions, and sinus tracts.

Patients were randomly assigned at baseline to receive a subcutaneous dose of lutikizumab at either 100 mg every other week, 300 mg every other week, or 300 mg every week, compared with placebo. The primary endpoint was HiSCR 50 at week 16, with a secondary endpoint of skin pain NRS30 at week 16 among patients with baseline NRS≥3.

Even with the proportion of patients experiencing severe disease, the trial found that those administered lutikizumab 300 mg weekly and 300 mg every other week experienced greater rates of improved skin pain compared to placebo; however, lutikizumab 100 mg every other week did not demonstrate superior efficacy than placebo.

In terms of safety, all of the dosing ranges were generally well-tolerated, according to the study. The percentage of patients experiencing treatment-emergent adverse events (TEAE) was 70.8% in the combined lutikizumab treatment cohorts compared with 75.0% for those in the placebo cohort. The most frequently reported TEAEs across lutikizumab cohorts were HS at 10.6%, diarrhea at 8.8 %, headache at 8.8%, pruritus at 6.2%, contact dermatitis at 5.3%, eczema at 5.3%, and nasopharyngitis at 5.3%. Serious AEs were reported in 5.3% of the combined lutikizumab treatment cohort compared with 2.5% with placebo.

Credit: AbbVie

The were no reports of deaths, no reports of neutropenia, and no observed cases of Grade 3 or 4 laboratory evaluations of neutropenia. There was one report of an infected stoma in the lutikizumab 300 mg every other week cohort, but no associated neutropenia.

"The burdens of HS are high and include long times to diagnosis, significant pain, disability, isolation, and reduced quality of life," study investigator Alexa B. Kimball, MD, MPH, of Beth Israel Deaconess Medical Center in Boston and professor of Dermatology, Harvard Medical School, said in a press release. "These results are encouraging and help us further understand the use of lutikizumab in patients with HS as we work to address the need for additional treatment options for patients living with this disease."

Reference

Lutikizumab Showed Positive Results in a Phase 2 Trial of Adults with Moderate to Severe Hidradenitis Suppurativa as Program Advances to Phase 3. AbbVie. News release. January 8, 2023. Accessed January 9, 2024. https://news.abbvie.com/2024-01-08-Lutikizumab-Showed-Positive-Results-in-a-Phase-2-Trial-of-Adults-with-Moderate-to-Severe-Hidradenitis-Suppurativa-as-Program-Advances-to-Phase-3