AbbVie's RINVOQ® Met Primary and All Ranked Secondary Endpoints in Phase 3 Study in Ankylosing Spondylitis

- ABBVie (NYSE: ABBV) today announced positive top-line results from the first of two studies of the Phase 3 SELECT-AXIS 2 clinical trial evaluating the efficacy and safety of RINVOQ ® (upadacitinib; 15 mg, once daily) in patients with active ankylosing spondylitis (AS) who had an inadequate response to biologic DMARD therapy. In this study, RINVOQ met its primary endpoint of Assessment in SpondyloArthritis International Society (ASAS) 40 response and all ranked secondary endpoints at week 14. 1 Significantly more RINVOQ-treated patients achieved ASAS40 response at week 14 compared to placebo (45 percent versus 18 percent; p

The results of SELECT-AXIS 1, a Phase 2/3 study in adult patients with ankylosing spondylitis who were naïve to bDMARDs and had an inadequate response or intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs), were used to support the European Commission approval of RINVOQ for the treatment of active ankylosing spondylitis in January 2021. ⁶

AbbVie will also announce the positive results of the second study of SELECT-AXIS 2 in adults with non-radiographic axial spondyloarthritis (nr-axSpA) later today. ¹

"Ankylosing spondylitis is a debilitating disease that can cause severe pain, stiffness, restricted mobility and lasting structural damage impacting patients' everyday life," said Michael Severino , M.D., vice chairman and president, AbbVie. "AbbVie is committed to improving standards of care for patients with rheumatic diseases. We are encouraged by these results that show RINVOQ was able to provide significant improvements in signs and symptoms, as well as other measures of disease activity, for patients living with ankylosing spondylitis who have already failed treatment with a biologic."

Treatment with RINVOQ resulted in statistically significant reductions in signs and symptoms of AS, including back pain and inflammation, as well as improvements in physical function and disease activity at week 14. ¹ Significantly more patients treated with RINVOQ achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) Low Disease Activity compared to those treated with placebo (44 percent versus 10 percent). ¹ A statistically significantly greater improvement in Magnetic Resonance Imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) Score (Spine) as measured by mean change from baseline was reported in the RINVOQ group versus the placebo group (-3.95 versus -0.04). ¹ Patients on RINVOQ experienced a significantly greater mean decrease from baseline in Patient's Assessment of Total Back Pain at week 14 than those on placebo (-3.00 versus -1.47). ¹ Additionally, patients treated with RINVOQ experienced significantly greater improvement in physical function as assessed by mean change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) compared to patients on placebo (-2.26 versus -1.09). ¹ All ranked secondary endpoints achieved p-values of 1

"Ankylosing spondylitis can have a profound impact on patients and severely limit their ability to perform daily tasks," said Filip Van den Bosch , SELECT-AXIS 2 investigator and professor in the Department of Rheumatology at the University Hospital of Ghent University. "There is a great need for effective treatment options for patients with an inadequate response to biologic DMARDs. These encouraging study results further demonstrate RINVOQ has the potential to impact the existing treatment paradigm for patients with ankylosing spondylitis."

Safety data were consistent with SELECT-AXIS 1, previous Phase 3 studies in other indications, and the known safety profile of RINVOQ, with no new risks identified. ^1-6 Through week 14, the most common adverse events (≥3 percent of patients) for RINVOQ were COVID-19 and headache. ¹ The proportion of patients with adverse events leading to discontinuation, serious adverse events and serious infections were 0 percent/2.8 percent/2.4 percent for RINVOQ and 1.4 percent/0.5 percent/0 percent for placebo, respectively. ¹ Serious infections included four events of COVID-19 and one of uveitis with RINVOQ; two patients on RINVOQ developed non-serious, mild or moderate herpes zoster limited to one dermatome. ¹ One patient treated with placebo developed a malignancy (tonsil cancer). ¹ No adjudicated major adverse cardiovascular events, venous thromboembolic events or deaths were reported in either group through week 14. ¹

Full results from the SELECT-AXIS-2 trial will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal.

About SELECT-AXIS 2 – Study 1 ^1,7
SELECT-AXIS 2 was conducted as a master study protocol that contains two standalone studies with randomization, data collection, analysis and reporting conducted independently. The Phase 3, randomized, placebo-controlled, double-blind studies are evaluating the efficacy and safety of RINVOQ compared with placebo on reduction of signs and symptoms in adult participants with active axSpA including bDMARD-IR AS (Study 1) and nr-axSpA (Study 2). Study 1 enrolled 420 who were randomized to receive RINVOQ for 104 weeks or placebo for 14 weeks followed by RINVOQ for 90 weeks. More information on this trial can be found at www.clinicaltrials.gov (NCT04169373).

About Axial Spondyloarthritis (axSpA)  
Axial spondyloarthritis is a chronic inflammatory disease that affects the spine, causing back pain, limited mobility, and structural damage. ⁸ It consists of two subsets that have been clinically defined as ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). ⁸ In ankylosing spondylitis, patients have definitive structural damage of the sacroiliac joints visible on x-rays. ⁸ Non-radiographic axial spondyloarthritis is clinically defined by the absence of definitive x-ray evidence of structural damage to the sacroiliac (SI) joint by plain x-ray. ⁸

About RINVOQ ^® (upadacitinib)  
Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. ^1,6,7,9-15 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. ⁶ RINVOQ is approved by the European Commission for adults (15 mg and 30 mg) and adolescents (15 mg) with moderate to severe atopic dermatitis. RINVOQ 15 mg is approved by the European Commission for adults with moderate to severe active rheumatoid arthritis, adults with active psoriatic arthritis and adults with active ankylosing spondylitis. RINVOQ 15 mg is also approved by the U.S. Food and Drug Administration (FDA) for adults with moderately to severely active rheumatoid arthritis. Phase 3 trials of RINVOQ in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing. ^9-15 Use of RINVOQ in non-radiographic axial spondyloarthritis is not approved and its safety and efficacy have not been established by regulatory authorities.

EU Indications and Important Safety Information About RINVOQ ^® (upadacitinib)   ⁶

Rheumatoid arthritis
RINVOQ is indicated for the treatment of moderate to severe active rheumatoid arthritis 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 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.

Ankylosing spondylitis
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 in adults and adolescents 12 years and older who are candidates for systemic therapy.

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
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 upadacitinib. The most frequent serious infections reported included pneumonia and cellulitis. Cases of bacterial meningitis have been reported. Among opportunistic infections, TB, multi-dermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis have been reported with upadacitinib. As there is a higher incidence of infections in patients ≥65 years of age, caution should be used when treating this population.

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 upadacitinib.

Vaccinations
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 upadacitinib, in agreement with current immunization guidelines.

Malignancy
The risk of malignancies, including lymphoma is increased in patients with rheumatoid arthritis (RA). Malignancies, including nonmelanoma skin cancer (NMSC), have been reported in patients treated with upadacitinib. Consider the risks and benefits of upadacitinib treatment prior to initiating therapy in patients with a known malignancy other than a successfully treated NMSC or when considering continuing upadacitinib therapy in patients who develop a malignancy.

Hematological abnormalities
Treatment should not be initiated, or should be temporarily interrupted, in patients with hematological abnormalities observed during routine patient management.

Cardiovascular risk
RA patients have an increased risk for cardiovascular disorders. Patients treated with upadacitinib should have risk factors (e.g., hypertension, hyperlipidemia) managed as part of usual standard of care.

Lipids
Upadacitinib 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 upadacitinib was associated with an increased incidence of liver enzyme elevation compared to placebo

Venous thromboembolisms
Events of deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors, including upadacitinib. Upadacitinib should be used with caution in patients at high risk for DVT/PE.

Adverse reactions
The most commonly reported adverse reactions in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis clinical trials (≥2% of patients in at least one of the indications) with upadacitinib 15 mg were upper respiratory tract infections, blood creatine phosphokinase (CPK) increased, alanine transaminase (ALT) increased, bronchitis, nausea, cough, aspartate transaminase (AST) increased, and hypercholesterolemia.

The most commonly reported adverse reactions in atopic dermatitis trials (≥2% of patients) with upadacitinib 15 mg or 30 mg were upper respiratory tract infection, acne, herpes simplex, headache, CPK increased, cough, folliculitis, abdominal pain, nausea, neutropenia, pyrexia, and influenza.

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.

Overall, the safety profile observed in patients with psoriatic arthritis or active ankylosing spondylitis treated with upadacitinib 15 mg was consistent with the safety profile observed in patients with RA.

In atopic dermatitis, dose-dependent increased risks of infection and herpes zoster were observed with upadacitinib. Based on limited data, there was a higher rate of overall adverse reactions with the upadacitinib 30 mg dose compared to the 15 mg dose in patients aged 65 years and older. The safety profile for upadacitinib 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. Dose-dependent changes in ALT increased and/or AST increased (≥ 3 x ULN), lipid parameters, CPK values (> 5 x ULN), and neutropenia (ANC 9 cells/L) associated with upadacitinib treatment were similar to what was observed in the rheumatologic disease clinical studies.

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

AbbVie's mission is to discover and deliver innovative medicines 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, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com . Follow @abbvie on Twitter , Facebook , LinkedIn or Instagram .

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, among others, 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 indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. 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 2020 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 to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

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