- 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
placebo1,2
- 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≥31,2
- HS is a chronic, often debilitating inflammatory skin
disease that can form lumps, abscesses and scars under the arms, in
the groin and other areas3,4,5,6,7
- 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:
Endpoints
(All at Week
16)
|
Response
(%)
|
Response (%);
Treatment Diff vs. PBO#
P-value+1
|
PBO
(N=40)
|
Luti 100 mg
EOW
(N=37)
|
Luti 300mg
EOW
(N=37)
|
Luti 300mg
EW
(N=39)
|
Primary
|
HiSCR 50
|
35.0
|
27.0
∆: -9.7
p=0.345
|
59.5
∆: 24.1
p=0.027
|
48.7
∆: 13.8
p=0.197
|
Secondary
|
Skin Pain
NRS30*
|
N=31
12.9
|
N=27
22.2
∆: 9.4
p=0.330
|
N=29
34.5
∆: 21.8
p=0.039
|
N=23
34.8
∆: 19.8
p=0.066
|
Additional
|
HiSCR 75
|
17.5
|
16.2
∆: -2.2
p=0.795
|
45.9
∆: 28.2
p=0.005
|
38.5
∆: 21.0
p=0.031
|
#Cochran-Mantel-Haenszel test adjusted for
the stratification factor (Baseline Hurley Stage <3 and 3)
+All p values are nominal
*Analyzed among patients with baseline Skin Pain NRS≥3
|
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.
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