- The positive opinion is based on results from the pivotal
Phase 3 SELECT-GCA trial that evaluated the efficacy and
safety of upadacitinib in adults with giant cell arteritis
(GCA)1
- The primary endpoint of sustained remission* and key
secondary endpoints, including reduction in disease flares, lower
cumulative steroid exposure, and complete remission,†
were met1
- GCA is an autoimmune disease that causes inflammation
of the large and medium cranial arteries, resulting in potentially
debilitating symptoms2
NORTH
CHICAGO, Ill., Feb. 28,
2025 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced that the European Medicines Agency's Committee for
Medicinal Products for Human Use (CHMP) adopted a positive opinion
recommending the approval of upadacitinib (RINVOQ®; 15
mg, once daily) for the treatment of adult patients with GCA.
The final European Commission decision is expected in the first
half of 2025. If approved, upadacitinib would be the first and only
oral advanced therapy for adults living with GCA.
"Giant cell arteritis is an inflammatory disease that, if left
untreated, can lead to severe outcomes like blindness, stroke or
aortic aneurysm,"2 said Prof. Dr. med. Wolfgang Schmidt, M.D., MACR, Waldfriede
Hospital, Department of Rheumatology, Berlin, Germany, and SELECT-GCA trial
investigator. "This positive opinion recognizes the unmet need for
adults living with giant cell arteritis, and I look forward to the
European Commission's final decision."
The CHMP positive opinion is supported by data from the pivotal
Phase 3 SELECT-GCA clinical trial evaluating the efficacy and
safety of upadacitinib in adults 50 years and older with
GCA.1 In the first study period, patients were
randomized to receive upadacitinib 7.5 mg or 15 mg in combination
with a 26-week corticosteroid taper regimen or placebo in
combination with a 52-week corticosteroid taper
regimen.1
During the 52-week, placebo-controlled period, the safety
profile of upadacitinib was generally consistent with that observed
in other approved indications.1
"The CHMP's positive opinion for upadacitinib for adults living
with giant cell arteritis is an important step toward our goal of
improving outcomes for patients suffering with this disease," said
Kori Wallace, M.D., Ph.D., vice
president, global head of immunology clinical development, AbbVie.
"We are committed to advancing the standards of care for
immune-mediated diseases and addressing unmet patient needs, today
and in the future."
RINVOQ is approved in the European Union (EU) for the treatment
of adults with radiographic axial spondylarthritis, nonradiographic
axial spondylarthritis, psoriatic arthritis, rheumatoid arthritis,
ulcerative colitis, Crohn's disease, and adults and adolescents
with atopic dermatitis.3 Use of upadacitinib in GCA is
not currently approved in the EU.
*Sustained remission is defined as having an absence of GCA
signs and symptoms from week 12 through week 52 and adherence to
the protocol-defined steroid taper over the course of the study
term.1
†Sustained complete
remission is defined as having an absence of GCA signs and symptoms
from week 12 through week 52, adherence to the protocol-defined
steroid taper, and normalization of both erythrocyte sedimentation
rate and high-sensitivity C-reactive protein from week 12 through
week 52.1
About Giant Cell Arteritis
Giant cell arteritis (GCA),
also known as temporal arteritis, is an autoimmune disease of
medium and large arteries, characterized by granulomatous
inflammation of the three-layered vessel wall, which affects
temporal and other cranial arteries as well as the aorta and other
large arteries.2,4 GCA can cause headache, jaw pain, and
changes in or loss of vision, including sudden and permanent loss
of vision.2 It is the most common vasculitis affecting
adults in western countries.2 White women over the age
of 50 – most commonly between the ages of 70 and 80 years – have
the highest risk of developing giant cell arteritis. Although women
are more likely than men to develop GCA, research suggests that men
are more likely to have ocular manifestations with their
disease.5
About SELECT-GCA
SELECT-GCA (M16-852) is a Phase 3,
multicenter, randomized, double-blind placebo-controlled study
designed to evaluate the safety and efficacy of upadacitinib in 428
patients with GCA. The study consists of two periods. The first
period, which is reported in this release, evaluated the efficacy
of upadacitinib in combination with a 26-week corticosteroid taper
regimen compared to placebo in combination with a 52-week
corticosteroid taper regimen. In addition, the study assessed the
safety and tolerability of upadacitinib in these patients. The
second period will evaluate the safety and efficacy of continuing
versus withdrawing upadacitinib in maintaining remission in
participants who achieved sustained remission in the first
period.6
Top-line results of the study were shared in April 2024. For more information regarding this
study, please visit ClinicalTrials.gov (Identifier
NCT03725202).
About Upadacitinib (RINVOQ®)
Discovered and
developed by AbbVie scientists, RINVOQ is a selective and
reversible JAK inhibitor that is being studied in several
immune-mediated inflammatory diseases.3,7 In human
cellular assays, RINVOQ preferentially inhibits signaling by JAK1
or JAK 1/3 with functional selectivity over cytokine receptors that
signal via pairs of JAK2.3 Upadacitinib (RINVOQ) is
being studied in Phase 3 clinical trials for alopecia areata, giant
cell arteritis, hidradenitis suppurativa, Takayasu arteritis,
systemic lupus erythematosus and vitiligo.8-13
EU Indications and Important Safety Information about
RINVOQ® (upadacitinib)3
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. Hepatic transaminases must be evaluated at
baseline and thereafter according to routine patient
management. 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.
Hypoglycemia in patients treated for diabetes
There have been reports of hypoglycemia following initiation of JAK
inhibitors, including RINVOQ, in patients receiving medication for
diabetes. Dose adjustment of anti-diabetic medication may be
necessary in the event that hypoglycemia occurs.
Medication Residue in Stool
Reports of medication residue in stool or ostomy output have
occurred in patients taking upadacitinib. Most reports described
anatomic (e.g., ileostomy, colostomy, intestinal resection) or
functional gastrointestinal conditions with shortened
gastrointestinal transit times. Patients should be instructed to
contact their healthcare professional if medication residue is
observed repeatedly. Patients should be clinically monitored, and
alternative treatment should be considered if there is an
inadequate therapeutic response.
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. With long-term exposure, skin papilloma was reported in
adolescents in the RINVOQ 15 mg and 30 mg groups.
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, neutropenia, rash,
pneumonia, hypercholesterolemia, bronchitis, AST increased,
fatigue, folliculitis, ALT 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 RINVOQ 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 Rheumatology
For more than 20 years, AbbVie has been dedicated to improving
care for people living with rheumatic diseases. Anchored by a
longstanding commitment to discovering and delivering
transformative therapies, we pursue cutting-edge science that
improves our understanding of promising new pathways and targets,
ultimately helping more people living with rheumatic diseases reach
their treatment goals. For more information, visit AbbVie in
rheumatology.
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 2024 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
- Blockmans D, Penn SK, Setty A, et al. LBA0001 Efficacy and
safety of upadacitinib in patients with giant cell arteritis
(SELECT-GCA): a double-blind, randomized controlled phase 3
trial. Ann Rheum Dis. 2024;83(suppl 1):232-233.
doi:10.1136/annrheumdis-2024-eular.LBA25
- Ameer MA, Peterfy RJ, Khazaeni B. Giant cell arteritis
(temporal arteritis). Updated August 8,
2023. https://www.ncbi.nlm.nih.gov/books/NBK459376/
- RINVOQ. Summary of Product Characteristics. Accessed
January 24, 2025.
https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf
- Weyand CM, Goronzy JJ. Immunology of giant cell arteritis.
Circ Res. 2023;132(2):238-250.
doi:10.1161/CIRCRESAHA.122.322128
- Giant cell arteritis. Arthritis
Foundation. Accessed January 9, 2025.
https://www.arthritis.org/diseases/giant-cell-arteritis
- AbbVie. Data on file: ABVRRTI78418.
- Pipeline. AbbVie. 2023. Accessed January 9, 2025.
https://www.abbvie.com/our-science/pipeline.html
- A study to evaluate the safety and efficacy of upadacitinib in
participants with giant cell arteritis (SELECT-GCA).
ClinicalTrials.gov identifier: NCT03725202. Accessed January
9, 2025. https://clinicaltrials.gov/ct2/show/NCT03725202
- A study to evaluate the efficacy and safety of upadacitinib in
participants with Takaysu arteritis (TAK) (SELECT-TAK).
ClinicalTrials.gov identifier: NCT04161898. Accessed January 9, 2025.
https://clinicaltrials.gov/study/NCT04161898
- Program to assess adverse events and change in disease activity
of oral upadacitinib in adult participants with moderate to severe
systemic lupus erythematosus (SELECT-SLE). ClinicalTrials.gov
identifier: NCT05843643. Accessed January 9,
2025. https://clinicaltrials.gov/study/NCT05843643
- A study to assess change in disease activity and adverse events
of oral upadacitinib in adult and adolescent participants with
moderate to severe hidradenitis suppurativa who have failed
anti-TNF therapy (Step-Up HS). ClinicalTrials.gov identifier:
NCT05889182. Accessed January 9,
2025. https://clinicaltrials.gov/study/NCT05889182
- A study to assess adverse events and effectiveness
of upadacitinib oral tablets in adult and adolescent
participants with vitiligo (Viti-Up). ClinicalTrials.gov
identifier: NCT06118411. Accessed January 9, 2025.
https://clinicaltrials.gov/study/NCT06118411
- A study to evaluate the safety and effectiveness
of upadacitinib tablets in adult and adolescent participants
with severe alopecia areata (UP-AA). ClinicalTrials.gov identifier:
NCT06012240. Accessed January 9, 2025.
https://clinicaltrials.gov/study/NCT06012240
|
International Media:
Ana Paula
Barboza
+1 (847)
938-2144
ana-paula.barboza@abbvie.com
U.S.
Media:
Shannelle
Fowler
+1 (773)
520-2106
shannelle.fowler@abbvie.com
|
Investors:
Liz Shea
+1 (862)
261-8130
liz.shea@abbvie.com
|
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