- At week 24, upadacitinib met the primary endpoint of percent
change from baseline in Facial Vitiligo Area Scoring Index (F-VASI)
with 11 mg and 22 mg doses versus placebo in adults with
non-segmental vitiligo (NSV)1
- At week 52, the percent reduction from baseline in F-VASI
was numerically greater than results at week 24 for all
upadacitinib doses1,2
- The safety profile was consistent with the known safety
profile for upadacitinib1,2
NORTH
CHICAGO, Ill., Oct. 11,
2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced that its Phase 2b study
evaluating upadacitinib (RINVOQ®) in adults with
non-segmental vitiligo (NSV) met the primary endpoint of percent
change from baseline in the Facial Vitiligo Area Scoring Index
(F-VASI) at week 24 with the 11 mg and 22 mg doses versus
placebo.1 The percent reduction from baseline in F-VASI
at week 52 was numerically greater than results at week 24 for all
upadacitinib doses.2 No new safety signals were
identified beyond the known safety profile for upadacitinib. Based
on these data, AbbVie is advancing its clinical program of
upadacitinib in vitiligo to Phase 3.
"There is a high unmet need in vitiligo, with no systemic
treatment options approved, leaving patients frustrated in seeking
options for re-pigmentation of the skin," said Roopal Thakkar, M.D., senior vice president,
development and regulatory affairs and chief medical officer,
AbbVie. "We will continue to apply our significant experience in
advancing research and driving innovation in treatments for
immune-mediated diseases, including underserved diseases with high
burden on patients, such as vitiligo."
At week 24, upadacitinib achieved the primary endpoint of
percent change from baseline (%CFB) in F-VASI with 11 mg and 22 mg
doses versus placebo. F-VASI is a tool that measures
re-pigmentation of the face and is used to assess the extent of
re-pigmentation and treatment response in clinical
trials.3 Higher response rates were also observed with
upadacitinib versus placebo in secondary endpoints, including
F-VASI 75 (≥75% reduction from baseline in F-VASI) at week 24 with
the 11 mg and 22 mg doses and Total Vitiligo Area Scoring Index
(T-VASI) 50 (≥50% reduction from baseline in T-VASI) at Week 24
with the 22 mg dose.
The mean percent reduction from baseline in F-VASI was
numerically greater at week 52 than results at week 24 for all
upadacitinib dose groups.2 In addition, response rates
observed for F-VASI 75 and T-VASI 50 at week 52 were numerically
greater than those at week 24 for all upadacitinib dose
groups.2
Week 24 Data
(Intent-to-Treat Population, MMRM/NRI-MI)
a,b
|
|
UPA 6 mg
(N=49)
|
UPA 11 mg
(N=47)
|
UPA 22 mg
(N=43)
|
PBO
(N=46)
|
Percent CFB in
F-VASI
Diff vs PBO
(p-value)
|
-22.0
-7.6
(p=0.304)
|
-35.6
-21.3
(p=0.005)
|
-34.0
-19.6
(p=0.013)
|
-14.4
|
F-VASI 75
(%)
Diff vs PBO
(p-value)
|
8.2
6.9
(p=0.100)
|
19.1
17.8
(p=0.002)
|
14.0
11.7
(p=0.026)
|
2.2
|
T-VASI 50
(%)
Diff vs PBO
(p-value)
|
6.1
3.7
(p=0.340)
|
6.4
3.8
(p=0.358)
|
11.6
9.1
(p=0.027)
|
2.2
|
Week 52 Data
(Intent-to-Treat Population, MMRM/NRI-MI)
a,c
|
Percent CFB in
F-VASI
|
-52.3
|
-62.8
|
-59.2
|
N/A
|
F-VASI 75
(%)
|
28.6
|
51.1
|
25.6
|
N/A
|
T-VASI 50
(%)
|
24.5
|
31.9
|
27.9
|
N/A
|
[a] Binary endpoints at Week 24
are analyzed using Cochrane-Mantel-Haenszel test. Missing data are
handled by non-responder imputation [NRI] incorporating multiple
imputation [MI] (NRI-MI) to handle missing data due to COVID-19.
Results for continuous endpoints are based on a
mixed-effects model for repeated measures
(MMRM).
|
[b] All p-values for upadacitinib
versus placebo are nominal. All statistical tests were performed at
a 2-sided statistical significance level of 0.1. No overall type I
error control was applied in this Phase 2 study.
|
[c] Table above features full
52-week data, which will be presented at an upcoming medical
meeting.
|
Among patients who continued upadacitinib treatment through week
52, %CFB in F-VASI and response rates for F-VASI 75 and T-VASI 50
were as follows:
Week 52 Data (As
Observed) a
|
|
UPA 6 mg
(N=38)
|
UPA 11 mg
(N=38)
|
UPA 22 mg
(N=29)
|
Percent CFB in
F-VASI
|
-52.7
|
-64.8
|
-60.8
|
F-VASI 75
(%)
|
36.8
|
63.2
|
37.9
|
T-VASI 50
(%)
|
31.6
|
39.5
|
41.4
|
[a] Table above features full
52-week data, which will be presented at an upcoming medical
meeting.
|
"Vitiligo impacts millions of people globally, and there is no
cure. The disease can have a great impact on patients' physical and
mental health, as depigmentation of the skin can be severe," said
Thierry Passeron, M.D., Ph.D., professor and chair, Department of
Dermatology, Université Côte d'Azur. "In vitiligo, it can take time
to see optimal skin re-pigmentation during treatment, which makes
long-term studies critical to providing valuable insights on a
treatment's meaningful impact for patients."
No new safety signals were observed beyond the known safety
profile for upadacitinib.1,2 Treatment-emergent adverse
event (TEAE) rates were generally similar with upadacitinib and
placebo in period 1 (most common TEAEs: COVID-19, acne, headache,
and nasopharyngitis). Numerically higher rates of serious TEAEs and
TEAEs leading to study drug discontinuation were observed in the
upadacitinib 22 mg group versus the other groups. One death
adjudicated as undetermined/unknown cause and deemed by the
investigator to have no reasonable possibility of being related to
study drug occurred in the upadacitinib 22 mg group (period 1). One
adjudicated event of nonfatal ischemic stroke occurred with
upadacitinib 11 mg (period 2) in a patient with known
cardiovascular risk factors. One event of malignancy (breast
cancer) occurred with upadacitinib 11 mg (period 2) in a patient
with positive family history of breast cancer. Throughout the
study, a single event of serious infection (COVID-19 pneumonia) was
reported in the upadacitinib 22 mg group. There were no adjudicated
events of venous thromboembolism, gastrointestinal perforation, or
active tuberculosis.2 The use of upadacitinib in
vitiligo is not approved and its safety and efficacy have not been
evaluated by regulatory authorities.
Vitiligo is a chronic, immune condition that affects up to 2% of
the global population.4 The disease is unique to each
patient, where white patches of depigmentation develop on the skin,
most often around the mouth and eyes, fingers and wrists, armpits
and groin.5 The most bothersome patches appear on the
face, which makes F-VASI a key measure of clinical improvement in
vitiligo for patients and dermatologists.3 NSV is the
most common form of vitiligo – affecting approximately eight in 10
people with vitiligo6 – in which patches appear on both
sides of the body symmetrically, and may spread over
time.5 People with vitiligo can also experience an
emotional and psychological burden that can impact their quality of
life.4
The 24-week data in this release and partial 52-week data are
being presented as an oral presentation during the European Academy
of Dermatology and Venerology (EADV) Congress in Berlin, Germany, on October 12, 2023. The partial 52-week data is
based on the data cutoff date of January 13,
2023. Approximately 58% of patients had an opportunity to
reach 52-week at that time. The full 52-week data in this release
will be presented at an upcoming medical meeting.
About the Phase 2 Study in Vitiligo1,2
The
52-week, Phase 2b multicenter,
randomized, double-blind, placebo-controlled study (NCT04927975)
comprises two periods. Enrolled patients were aged 18–66 years with
NSV, a Facial Vitiligo Area Scoring Index (F-VASI) of 1.1 and a
Total Vitiligo Area Scoring Index (T-VASI) of 22, both mean scores
at baseline. In period one, 185 patients (18 to 65 years old) were
randomly assigned to once-daily upadacitinib 22 mg (N=43),
upadacitinib 11 mg (N=47), upadacitinib 6 mg (N=49), or placebo
(N=46) for 24 weeks of treatment. 166 patients (89.7%) continued to
a 28-week blinded extension (period two). In period two, patients
receiving upadacitinib during period one continued their respective
regimens (upadacitinib 22 mg, N=33; upadacitinib 11 mg, N=45;
upadacitinib 6 mg, N=45); patients who received placebo in period
one were pre-assigned to receive either upadacitinib 11 mg (N=21)
or upadacitinib 22 mg (N=22) in period 2.
About
RINVOQ® (upadacitinib)8
Discovered and developed by AbbVie scientists, RINVOQ is a JAK
inhibitor with seven approved indications and is currently being
studied in several immune-mediated diseases.7,8 In human
cellular assays, RINVOQ preferentially inhibits signaling by JAK1
or JAK1/3 with functional selectivity over cytokine receptors that
signal via pairs of JAK2.8 The relevance of inhibition
of specific JAK enzymes to therapeutic effectiveness and safety is
not currently known.
Use of upadacitinib in vitiligo is not approved and its safety
and efficacy have not been evaluated by regulatory authorities.
EU Indications and Important Safety Information about
RINVOQ® (upadacitinib)8
Indications
Rheumatoid arthritis
RINVOQ is indicated for the treatment of moderate to severe active
rheumatoid arthritis (RA) in adult patients who have responded
inadequately to, or who are intolerant to one or more
disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ may be used
as monotherapy or in combination with methotrexate.
Psoriatic arthritis
RINVOQ is indicated for the
treatment of active psoriatic arthritis (PsA) in adult patients who
have responded inadequately to, or who are intolerant to one or
more DMARDs. RINVOQ may be used as monotherapy
or in combination with methotrexate.
Axial spondyloarthritis
Non-radiographic axial spondyloarthritis (nr-axSpA)
RINVOQ is indicated for the treatment of active non-radiographic
axial spondyloarthritis in adult patients with objective signs of
inflammation as indicated by elevated
C-reactive protein (CRP) and/or magnetic resonance
imaging (MRI), who have responded inadequately to nonsteroidal
anti- inflammatory drugs (NSAIDs).
Ankylosing spondylitis (AS, radiographic axial spondyloarthritis)
RINVOQ is indicated
for the treatment of active
ankylosing spondylitis in adult patients
who have responded inadequately to conventional therapy.
Atopic dermatitis
RINVOQ is indicated
for the treatment of moderate
to severe atopic dermatitis (AD) in adults and
adolescents 12 years and older who are candidates for systemic
therapy.
Ulcerative
colitis
RINVOQ is indicated for the treatment
of adult patients
with moderately to severely active ulcerative
colitis (UC) who have had an inadequate response, lost response or
were intolerant to either conventional therapy or a biologic
agent.
Crohn's disease
RINVOQ is indicated for the treatment
of adult patients with moderately to severely active Crohn's
disease who have had an inadequate response, lost response or were
intolerant to either conventional therapy or a biologic agent.
Important Safety Information
Contraindications
RINVOQ is contraindicated in patients hypersensitive to the active substance or to any of the excipients,
in patients with active tuberculosis (TB) or active serious
infections, in patients with severe hepatic impairment, and during
pregnancy.
Special warnings and precautions for
use
RINVOQ should only be used if no suitable treatment
alternatives are available in patients:
- 65 years of age and older;
-
patients with history of atherosclerotic
cardiovascular (CV) disease or other CV
risk factors (such as current or past long-time
smokers);
-
patients with malignancy risk factors (e.g. current malignancy or history of malignancy)
Use in patients 65 years of age and older
Considering the increased risk of MACE, malignancies, serious
infections, and all-cause mortality in patients ≥65 years of age,
as observed in a large randomised study of tofacitinib (another JAK
inhibitor), RINVOQ should only be used in these patients if no
suitable treatment alternatives are available. In patients ≥65
years of age, there is an increased risk of adverse reactions with
RINVOQ 30 mg once daily. Consequently, the recommended dose for
long-term use in this patient population is 15 mg once daily.
Immunosuppressive medicinal products
Use in combination with other potent
immunosuppressants is not recommended.
Serious infections
Serious and sometimes fatal infections have been reported in
patients receiving RINVOQ. The most frequent serious infections
reported included pneumonia and
cellulitis. Cases of bacterial meningitis and
sepsis have been reported with RINVOQ. Among opportunistic
infections, TB, multidermatomal herpes zoster,
oral/esophageal candidiasis, and cryptococcosis have been
reported. RINVOQ should not be initiated in patients with an
active, serious infection, including localized infections. RINVOQ
should be interrupted if a patient develops a serious or
opportunistic infection until the infection is controlled. A higher
rate of serious infections was observed with RINVOQ 30 mg compared
to 15 mg. As there is a higher incidence of infections in the
elderly and patients with diabetes in general, caution should be
used when treating these populations. In patients ≥65 years of age,
RINVOQ should only be used if no suitable treatment alternatives
are available.
Tuberculosis
Patients should be screened for TB before starting RINVOQ. RINVOQ
should not be given to patients with active TB. Anti-TB therapy may
be appropriate for select patients in consultation with a physician
with expertise in the treatment of TB. Patients should be monitored
for the development of signs and symptoms of TB.
Viral reactivation
Viral reactivation, including cases of herpes zoster, was reported
in clinical studies. The risk of herpes zoster appears to be higher
in Japanese patients treated with RINVOQ. Consider interruption of
RINVOQ if the patient develops herpes zoster until the episode
resolves. Screening for viral hepatitis and monitoring for
reactivation should occur before and during therapy. If hepatitis B
virus DNA is detected, a liver specialist should be consulted.
Vaccination
The use of live, attenuated vaccines during or immediately prior to
therapy is not recommended. It is recommended that patients be
brought up to date with all immunizations, including prophylactic
zoster vaccinations, prior to initiating RINVOQ, in agreement with
current immunization guidelines.
Malignancy
Lymphoma and other malignancies have been reported in patients
receiving JAK inhibitors, including RINVOQ. In a large randomised
active–controlled study of tofacitinib (another JAK inhibitor) in
RA patients ≥50 years of age with ≥1 additional CV risk factor, a
higher rate of malignancies, particularly lung cancer, lymphoma,
and non-melanoma skin cancer (NMSC), was observed with tofacitinib
compared to tumour necrosis factor (TNF) inhibitors. A higher rate
of malignancies, including NMSC, was observed with RINVOQ 30 mg
compared to 15 mg. Periodic skin examination is recommended for all
patients, particularly those with risk factors for skin cancer. In
patients ≥65 years of age, patients who are current or past
long-time smokers, or patients with other malignancy risk factors
(e.g., current malignancy or history of malignancy), RINVOQ should
only be used if no suitable treatment alternatives are
available.
Hematological abnormalities
Treatment should not be initiated, or should be temporarily interrupted, in patients with hematological
abnormalities observed during routine patient management.
Gastrointestinal Perforations
Events of diverticulitis and gastrointestinal perforations have
been reported in clinical trials and from post–marketing sources.
RINVOQ should be used with caution in patients who may be at risk
for gastrointestinal perforation (e.g., patients with diverticular
disease, a history of diverticulitis, or who are taking
nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, or
opioids. Patients with active Crohn's disease are at increased risk
for developing intestinal perforation. Patients presenting with new
onset abdominal signs and symptoms should be evaluated promptly for
early identification of diverticulitis or gastrointestinal
perforation.
Major adverse cardiovascular events
MACE were observed in clinical studies of RINVOQ. In a large
randomised active-controlled study of tofacitinib (another JAK
inhibitor) in RA patients ≥50 years of age with ≥1 additional CV
risk factor, a higher rate of MACE, defined as CV death, non-fatal
myocardial infarction and non-fatal stroke, was observed with
tofacitinib compared to TNF inhibitors. Therefore, in patients ≥65
years of age, patients who are current or past long-time smokers,
and patients with history of atherosclerotic CV disease or other CV
risk factors, RINVOQ should only be used if no suitable treatment
alternatives are available.
Lipids
RINVOQ treatment was associated with dose-dependent increases in lipid parameters, including total
cholesterol, low-density lipoprotein cholesterol, and high-density
lipoprotein cholesterol.
Hepatic transaminase elevations
Treatment with RINVOQ was associated with an increased incidence of
liver enzyme elevation. If alanine transaminase (ALT) or aspartate
transaminase (AST) increases are observed and drug-induced liver
injury is suspected, RINVOQ should be interrupted until this
diagnosis is excluded.
Venous thromboembolism
Events of deep venous thrombosis (DVT) and pulmonary embolism (PE)
were observed in clinical trials for RINVOQ. In a large randomised
active-controlled study of tofacitinib (another JAK inhibitor) in
RA patients ≥50 years of age with ≥1 additional CV risk factor, a
dose–dependent higher rate of VTE including DVT and PE was observed
with tofacitinib compared to TNF inhibitors. In patients with CV or
malignancy risk factors, RINVOQ should only be used if no suitable
treatment alternatives are available. In patients with known VTE
risk factors other than CV or malignancy risk factors (e.g.
previous VTE, patients undergoing major surgery, immobilisation,
use of combined hormonal contraceptives or hormone replacement
therapy, and inherited coagulation disorder), RINVOQ should be used
with caution. Patients
should be re-evaluated periodically to assess
for changes in VTE risk. Promptly evaluate
patients with signs and symptoms of VTE and discontinue RINVOQ in
patients with suspected VTE.
Hypersensitivity reactions
Serious hypersensitivity reactions such as anaphylaxis and angioedema have been reported
in patients receiving RINVOQ. If a clinically significant
hypersensitivity reaction occurs, discontinue RINVOQ and institute
appropriate therapy.
Adverse reactions
The most commonly reported adverse
reactions in RA, PsA, and axSpA clinical trials (≥2% of patients in
at least one of the indications) with RINVOQ 15 mg were upper
respiratory tract infections, blood creatine phosphokinase (CPK)
increased, ALT increased, bronchitis, nausea, neutropenia, cough,
AST increased, and hypercholesterolemia. Overall, the safety
profile observed in patients with psoriatic arthritis or active
axial spondyloarthritis treated with RINVOQ 15 mg was consistent
with the safety profile observed in patients with RA.
The most commonly reported adverse reactions in AD trials (≥2%
of patients) with RINVOQ 15 mg or 30 mg were upper respiratory
tract infection, acne, herpes simplex, headache, blood CPK
increased, cough, folliculitis, abdominal pain, nausea,
neutropenia, pyrexia, and influenza. Dose dependent increased risks
of infection and herpes zoster were observed with RINVOQ. The
safety profile for RINVOQ 15 mg in adolescents was similar to that
in adults. The safety and efficacy of the 30 mg dose in adolescents
are still being investigated.
The most commonly reported adverse reactions in the UC and CD
trials (≥3% of patients) with RINVOQ 45 mg, 30 mg or 15 mg were
upper respiratory tract infection, pyrexia, blood CPK increased,
anemia, headache, acne, herpes zoster, neutropaenia, rash,
pneumonia, hypercholesterolemia, bronchitis, aspartate transaminase
increased, fatigue, folliculitis, alanine transaminase increased,
herpes simplex, and influenza.
The overall safety profile observed in patients with UC was
generally consistent with that observed in patients with RA.
Overall, the safety profile observed in patients with CD treated
with RINVOQ was consistent with the known safety profile for
RINVOQ.
The most common serious adverse reactions were serious
infections.
The safety profile of upadacitinib with long–term treatment was
generally similar to the safety profile during the
placebo–controlled period across indications.
This is not a complete summary
of all safety information.
See RINVOQ
full Summary of Product Characteristics (SmPC) at www.ema.europa.eu
Globally, prescribing information varies; refer to the individual country
product label for complete information.
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. For more information, visit
AbbVie in dermatology.
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 – and 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
- Hamzavi, I., et al. Efficacy and Safety of Upadacitinib in a
Phase 2, Double-Blind, Dose-Ranging Study of Adults With Extensive
Non-Segmental Vitiligo. 2023 European Academy of Dermatology and
Venereology (EADV) Congress. October
2023.
- AbbVie. Data on file: ABVRRTI77148
- Kitchen H, et al. Meaningful Changes in What Matters to
Individuals with Vitiligo: Content Validity and Meaningful Change
Thresholds of the Vitiligo Area Scoring Index (VASI). Dermatol Ther
(Heidelb). 2022 Jul;12(7):1623-1637. doi:
10.1007/s13555-022-00752-8. Epub 2022 Jun 30. PMID: 35773559;
PMCID: PMC9245872.
- Krüger C, Schallreuter KU. Int J Dermatol.
2012;51(10):1206–12
- National Health Service. Vitiligo. Available at:
https://www.nhs.uk/conditions/vitiligo/#:~:text=In%20non%2Dsegmental%20vitiligo%20(also,openings%2C%20such%20as%20the%20eyes.
Accessed September 2023.
- Gandhi K, Ezzedine K, Anastassopoulos KP, Patel R,
Sikirica V, Daniel SR, Napatalung L, Yamaguchi Y, Baik R, Pandya
AG. Prevalence of Vitiligo Among Adults in the United States. JAMA Dermatol. 2022
Jan 1;158(1):43-50. doi:
10.1001/jamadermatol.2021.4724. PMID: 34787670; PMCID:
PMC8600454.
- Pipeline – Our Science | AbbVie. 2023. Available at:
https://www.abbvie.com/our-science/pipeline.html. Accessed
September 2023.
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland
GmbH & Co KG. Available at: www.ema.europa.eu
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