Lutikizumab Showed Positive Results in a Phase 2 Trial of Adults with Moderate to Severe Hidradenitis Suppurativa as Program Advances to Phase 3

• Phase 2 data in adults with hidradenitis suppurativa (HS) who had previously failed anti-TNF therapy who received lutikizumab (ABT-981) 300 mg weekly or 300 mg every other week showed higher response rates in HiSCR 50 at week 16 than those treated with placebo^1,2
• Higher response rates were also observed in patients receiving lutikizumab 300 mg weekly or 300 mg every other week than those treated with placebo in the secondary endpoint of skin pain NRS30 at week 16 among patients with baseline NRS≥3^1,2
• HS is a chronic, often debilitating inflammatory skin disease that can form lumps, abscesses and scars under the arms, in the groin and other areas^3,4,5,6,7
• Program reflects AbbVie's leadership in immunology and history of investigating new options for patients with HS, where there remains a significant unmet medical need

NORTH CHICAGO, Ill., Jan. 8, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced Phase 2 results showing adults with moderate to severe hidradenitis suppurativa (HS) who had previously failed anti-TNF therapy who received lutikizumab (ABT-981) 300 mg every other week or 300 mg weekly achieved higher response rates (59.5 percent, nominal p=0.027 and 48.7 percent, nominal p=0.197, respectively) than placebo (35.0 percent) in the primary endpoint of achieving HS Clinical Response (HiSCR 50) at week 16. Based on these data, AbbVie will advance its clinical program of lutikizumab in HS to Phase 3.^1,2

Lutikizumab is AbbVie's investigational, dual-variable-domain interleukin (IL) 1α/1β antagonist. Studies have shown IL 1α and 1β are elevated in HS lesions.⁸

"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. "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 3."

This study was a 16-week, Phase 2, randomized, double-blind, parallel group, placebo controlled, dose-ranging, multicenter study that evaluated the safety and efficacy of lutikizumab in 153 adult patients with moderate to severe HS who had previously failed anti-TNF therapy. Most patients (70.6 percent) had severe baseline Hurley Stage 3 disease – the most extensive form of HS – characterized by scarring, lesions and sinus tracts. Patients were randomized at baseline to receive one of three subcutaneous doses of lutikizumab (100 mg every other week, 300 mg every other week, or 300 mg every week) or placebo. The study's primary endpoint was an achievement of HiSCR 50 at week 16, and the secondary endpoint was skin pain NRS30 at week 16 among subjects with baseline NRS≥3.¹  

In addition to achieving higher response rates in the primary endpoint and despite most patients having severe disease, the trial also showed patients receiving lutikizumab 300 mg weekly and 300 mg every other week achieved higher rates of improved skin pain via NRS30 and HiSCR75, a higher threshold of HS clinical response, compared to placebo. Lutikizumab 100 mg every other week did not show greater efficacy compared to placebo.¹

Results from select endpoints are as follows:

All doses were generally well-tolerated. The percentage of subjects with treatment-emergent adverse events (TEAE) were generally similar across combined lutikizumab treatment arms (70.8 percent) and placebo (75.0 percent) with the most common being HS (10.6 percent), diarrhea (8.8 percent), headache (8.8 percent), pruritus (6.2 percent), contact dermatitis (5.3 percent), eczema (5.3 percent), and nasopharyngitis (5.3 percent) in the combined lutikizumab treatment group. Serious adverse events (SAEs) occurred in 5.3 percent of the combined lutikizumab treatment group and in 2.5 percent in the placebo group. There were no deaths, no events of neutropenia reported, and no Grade 3 or 4 laboratory evaluations of neutropenia observed. Throughout the study, one event of serious infection (infected stoma) was reported in lutikizumab 300 mg every other week, with no associated neutropenia, deemed by the investigator as having no reasonable possibility of being related to study drug. There was one instance of T-cell lymphoma (lutikizumab 300 mg every week) reported in a patient with pre-existing risk factors, including HS⁹ and ongoing cigarette smoking. There were no dose-dependent trends in any TEAEs, SAEs, infections, or serious infections.

"The burdens of HS are high and include long times to diagnosis, significant pain, disability, isolation, and reduced quality of life," said Alexa B. Kimball, M.D., MPH, a study investigator from Beth Israel Deaconess Medical Center in Boston and Professor of Dermatology, Harvard Medical School.^10,11,12 "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."

HiSCR 50 at week 16, the primary endpoint of this study, is a measure that represents patients who achieve at least a 50 percent reduction at week 16 in the total abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to baseline. Similarly, HiSCR 75 represents the achievement of at least a 75 percent reduction in AN count at week 16 with no increase in draining fistula count relative to baseline. The secondary endpoint, NRS30 at week 16, defines the achievement of at least a 30 percent reduction and at least 1-unit reduction from baseline in NRS (Numeric Rating Scale) at week 16 as assessed by patient global assessment for skin pain, among subjects with baseline NRS≥3.¹³

These data will be presented at a future medical congress. Additional information about the program can be found on clinicaltrials.gov under the identifier NCT05139602.²

About Hidradenitis Suppurativa
Hidradenitis Suppurativa, sometimes referred to as "acne inversa" by dermatologists, is an inflammatory, chronic, recurrent, progressive disease that causes irreversible skin damage and disability due to the formation of painful cysts, abscesses and draining fistula.^3,4,5,6,7 While advances in treatment have been made, limited treatment options are available. Globally, HS affects up to 1 percent of the population¹⁴ and can take on average 7-10 years for a person to be diagnosed.^15,16

About Lutikizumab (ABT-981) 
Lutikizumab (ABT-981) is a dual-variable-domain interleukin (IL) 1α/1β antagonist being investigated in several immune-mediated diseases, including HS and ulcerative colitis. Studies have shown IL 1α and 1β are elevated in HS lesions.⁸ Lutikizumab is an investigational agent and is not approved by regulatory authorities. Safety and efficacy have not been established.

About AbbVie in Dermatology
For more than a decade, AbbVie has worked to uncover new solutions and improve care for people with serious skin diseases, including psoriasis, psoriatic arthritis, hidradenitis suppurativa and atopic dermatitis. With a broad clinical trial program, we continue to actively research and adapt to the evolving needs of the dermatology community and advance our pipeline to help people achieve their treatment goals and live beyond their skin disease.

About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – in addition to products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.

Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2022 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References

¹ AbbVie Data on File ABVRRTI77645.
² A Study to Assess Disease Activity and Safety of Subcutaneous Lutikizumab (ABT-981) in Adult Participants With Moderate to Severe Hidradenitis Suppurativa Who Have Failed Anti-Tumor Necrosis Factor (TNF) Therapy. ClinicalTrials.gov. Available at: clinicaltrials.gov/study/NCT05139602. Accessed December 8, 2023.
³ Negus D, Ahn C, Huang W. An update on the pathogenesis of hidradenitis suppurativa: implications for therapy. Expert Rev Clin Immunol. 2018;14(4):275-283.
⁴ Patel ZS et al. Pain, Psychological Comorbidities, Disability, and Impaired Quality of Life in Hidradenitis Suppurativa [corrected]. Curr Pain Headache Rep. 2017;21(12):49.
⁵ Chen WT, et al. JAMA Dermatol. 2019 Jul 10.
⁶ Jemec G. Hidradenitis Suppurativa. N Engl J Med. 2012; 366:158-64.
⁷ Kimball A, et al. Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa. New England Journal of Medicine 375.5; 2016: 422-34.
⁸ VanderZee et al British Journal of Dermatology (2011) 164, p1292–98; Kanni et al (2015) PLoS ONE 10(6): e0130522.
⁹ Tannenbaum R, Strunk A, Garg A. Association Between Hidradenitis Suppurativa and Lymphoma. JAMA Dermatol. 2019 May 1;155(5):624-625.
¹⁰ Jemec G. Hidradenitis Suppurativa. N Engl J Med. 2012; 366:158-64.
¹¹ Hamzavi HI, et al. J Am Acad Dermatol 2017;77:1038–46.
¹² Von der Werth. Br J Dermatol 2001;144:809–13.
¹³ Assessing the validity and clinical meaningfulness of skin pain response (NRS30) assessed using numerical rating scale in hidradenitis suppurativa: Results from the SUNSHINE and SUNRISE trials. Journal of the American Academy of Dermatology, Accessed December 8, 2023.
¹⁴ Egeberg A, et al. JAMA Dermatol 2016;152:429–34.
¹⁵ Garg A, et al. JAMA Dermatol. 2018 Jul 1;154(7):814-818.
¹⁶ Saunte DM, et al. Br J Dermatol 2015;173:1546–9.

SOURCE AbbVie