AbbVie announced positive Phase 2 results for lutikizumab (ABT-981), an investigational dual-variable-domain interleukin (IL) 1α/1β antagonist, in adults with moderate to severe hidradenitis suppurativa (HS) who had previously failed anti-TNF therapy. The encouraging data have prompted the company to advance the clinical program to Phase 3 trials.
Primary Endpoint Results Exceed Placebo
In the 16-week, randomized, double-blind, placebo-controlled study of 153 adult patients, lutikizumab demonstrated superior efficacy compared to placebo. Patients receiving lutikizumab 300 mg every other week achieved a 59.5% response rate in the primary endpoint of HiSCR 50 at week 16, with a nominal p-value of 0.027 compared to placebo's 35.0% response rate. The 300 mg weekly dose showed a 48.7% response rate (nominal p=0.197), while the lower 100 mg every other week dose did not demonstrate greater efficacy than placebo.
"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," said study author Alexa B. Kimball, MD, MPH, a professor of Dermatology at Harvard Medical School and President and CEO of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center in Boston.
Targeting Elevated Inflammatory Pathways
Lutikizumab specifically targets IL-1α and IL-1β, cytokines that studies have shown are elevated in HS lesions. This mechanism of action addresses the underlying inflammatory pathways driving the disease, which causes painful cysts, abscesses, and draining fistulas primarily in areas such as under the arms and groin.
The study population represented patients with significant disease burden, with 70.6% having severe baseline Hurley Stage 3 disease – the most extensive form of HS characterized by scarring, lesions, and sinus tracts.
Secondary Endpoints Show Additional Benefits
Beyond the primary endpoint, patients receiving the higher lutikizumab doses also achieved superior results in secondary measures. Both the 300 mg weekly and 300 mg every other week doses demonstrated higher rates of improved skin pain via NRS30 and HiSCR75, a more stringent threshold requiring at least 75% reduction in abscess and inflammatory nodule count.
Safety Profile Remains Favorable
The treatment demonstrated a generally well-tolerated safety profile across all doses. Treatment-emergent adverse events occurred in 70.8% of combined lutikizumab treatment arms compared to 75.0% in the placebo group. The most common adverse events in the lutikizumab group included HS (10.6%), diarrhea (8.8%), headache (8.8%), pruritus (6.2%), contact dermatitis (5.3%), eczema (5.3%), and nasopharyngitis (5.3%).
Serious adverse events occurred in 5.3% of the combined lutikizumab treatment group versus 2.5% in the placebo group. Notably, there were no deaths, no events of neutropenia reported, and no Grade 3 or 4 laboratory evaluations of neutropenia observed. One serious infection (infected stoma) was reported in the lutikizumab 300 mg every other week group, deemed by investigators as having no reasonable possibility of being related to the study drug.
Addressing Significant Unmet Medical Need
"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," said Roopal Thakkar, M.D., senior vice president, chief medical officer, global therapeutics, AbbVie.
HS affects up to 1% of the global population and can take an average of 7-10 years for proper diagnosis. The disease creates substantial burdens including significant pain, disability, isolation, and reduced quality of life, highlighting the critical need for additional therapeutic options.
Clinical Program Advancement
Based on these Phase 2 results, AbbVie will leverage its more than 25 years of expertise in immune-mediated diseases to advance lutikizumab to Phase 3 trials in HS. The data will be presented at a future medical congress, with additional program information available on clinicaltrials.gov under identifier NCT05139602.
