AbbVie Advances Upadacitinib to Phase 3 Clinical Trials in Systemic Lupus Erythematosus

• Results of the M19-130 (SLEek) Phase 2 trial of upadacitinib given alone or as a combination therapy (ABBV-599) met the primary endpoint of systemic lupus erythematosus (SLE) Responder Index (SRI-4) and steroid dose less than or equal to 10 mg prednisone equivalent once per day at week 24 in patients with moderately to severely active SLE ^{1   ,   2}
• No new safety signals were identified with upadacitinib, and a similar safety profile was observed for the combination therapy (ABBV-599) as for treatment with upadacitinib alone ^{2, 3   ,   4   ,   5   ,   6   ,   7}
• SLE is a complex autoimmune disorder in which the body's immune system attacks healthy tissue of the musculoskeletal system, skin, kidneys, lungs and other critical organs, leading to symptoms such as fatigue, joint pain and impaired function. ^{8   ,   9}

- ABBVie (NYSE: ABBV) today announced topline results from a Phase 2 study of upadacitinib (RINVOQ ® 30 mg) given alone or as combination therapy (ABBV-599) with a Bruton's Tyrosine Kinase inhibitor (elsubrutinib, 60 mg), once daily in patients with moderately to severely active systemic lupus erythematosus (SLE). 1 The SLEek study met the primary endpoint of SLE Responder Index (SRI-4) and steroid dose less than or equal to 10 mg prednisone equivalent once per day at week 24 in the upadacitinib 30 mg group. 1,2 Based on the results, ABBVie is advancing its clinical program of upadacitinib in SLE to Phase 3.

"Systemic lupus erythematosus is a very unpredictable life-long condition and the way it affects a patient can change over time. Therefore, there is a critical need for additional treatment options," said Roopal Thakkar , M.D., senior vice president, development and regulatory affairs and chief medical officer, AbbVie. "With a quarter-century of experience and commitment to the treatment of rheumatic diseases, our focus remains on areas of high unmet need like systemic lupus erythematosus, and we look forward to further evaluation of the potential benefits that upadacitinib could bring to patients."

A total of 341 participants enrolled in the Phase 2 study and were subsequently divided into five experimental groups according to treatment regimen (upadacitinib in combination with placebo; upadacitinib, at two different doses, combined with elsubrutinib; elsubrutinib in combination with placebo; placebo only). ¹ The primary outcome measure was achievement of the SRI-4 with a steroid dose less than or equal to 10 mg prednisone equivalent once daily at week 24. ¹ SRI-4 is defined as a greater or equal to 4-point reduction in SLE Disease Activity Index 2000 score without worsening of the overall condition or the development of significant disease activity in new organ systems. ¹

The safety results for the upadacitinib 30 mg arm of the study were generally consistent with the known safety profile of upadacitinib, with no new safety signals identified. ^2-7 Types of adverse events reported with upadacitinib combined with elsubrutinib were similar to those reported for patients treated with upadacitinib alone. ² Full results from the study will be presented at a future medical congress. Use of upadacitinib and elsubrutinib in SLE are not approved and their safety and efficacy have not been evaluated by regulatory authorities.

Additional information about the study can be found at www.clinicaltrials.gov under the identifier NCT03978520.

About Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a complex, multi-organ, autoimmune disorder characterized by the production of pathogenic autoantibodies and tissue deposition of immune complexes. ^8,9 In SLE, the body's immune system attacks healthy tissue of the musculoskeletal system, skin, kidneys, and other critical organs, leading to symptoms such as fatigue, joint pain and impaired function. ^8,9 The prevalence of SLE is higher in women compared to men, and SLE occurs more frequently in people of color. ^10,11

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. ^{3-7,12,13,14,15,16,17,18,19} Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK-1 vs JAK-2, JAK-3 and TYK-2. ³ The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known. ³

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. ^3-7,12-19 The use of upadacitinib in systemic lupus erythematosus is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

US Indications and Important Safety Information about RINVOQ ^® (upadacitinib) ³

USES

RINVOQ is a prescription medicine used to treat:

• Adults with moderate to severe rheumatoid arthritis (RA) when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used and did not work well or could not be tolerated.
• Adults with active psoriatic arthritis (PsA) when 1 or more medicines called TNF blockers have been used and did not work well or could not be tolerated.
• Adults with moderate to severe ulcerative colitis (UC) when 1 or more medicines called TNF blockers have been used and did not work well or could not be tolerated.
• Adults with active ankylosing spondylitis (AS) when 1 or more medicines called TNF blockers have been used and did not work well or could not be tolerated.
• Adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation when a TNF blocker medicine has been used and did not work well or could not be tolerated.

It is not known if RINVOQ is safe and effective in children with juvenile idiopathic arthritis, psoriatic arthritis, ulcerative colitis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis.

• Adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis [AD]) that did not respond to previous treatment and their eczema is not well controlled with other pills or injections, including biologic medicines, or the use of other pills or injections is not recommended.

RINVOQ is safe and effective in children 12 years of age and older weighing at least 88 pounds (40 kg) with atopic dermatitis.

It is not known if RINVOQ is safe and effective in children under 12 years of age with atopic dermatitis.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about RINVOQ?

RINVOQ may cause serious side effects, including:

• Serious infections. RINVOQ can lower your ability to fight infections. Serious infections have happened while taking RINVOQ, including tuberculosis (TB) and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections. Your healthcare provider (HCP) should test you for TB before starting RINVOQ and check you closely for signs and symptoms of TB during treatment with RINVOQ. You should not start taking RINVOQ if you have any kind of infection unless your HCP tells you it is okay. If you get a serious infection, your HCP may stop your treatment until your infection is controlled. You may be at higher risk of developing shingles (herpes zoster).
• Increased risk of death in people 50 years and older who have at least 1 heart disease (cardiovascular) risk factor.
• Cancer and immune system problems. RINVOQ may increase your risk of certain cancers. Lymphoma and other cancers, including skin cancers, can happen. Current or past smokers are at higher risk of certain cancers, including lymphoma and lung cancer. Follow your HCP's advice about having your skin checked for skin cancer during treatment with RINVOQ. Limit the amount of time you spend in sunlight. Wear protective clothing when you are in the sun and use sunscreen.
• Increased risk of major cardiovascular (CV) events, such as heart attack, stroke, or death, in people 50 years and older who have at least 1 heart disease (CV) risk factor, especially if you are a current or past smoker.
• Blood clots. Blood clots in the veins of the legs or lungs and arteries can happen with RINVOQ. This may be life-threatening and cause death. Blood clots in the veins of the legs and lungs have happened more often in people who are 50 years and older and with at least 1 heart disease (CV) risk factor.
• Allergic reactions. Symptoms such as rash (hives), trouble breathing, feeling faint or dizzy, or swelling of your lips, tongue, or throat, that may mean you are having an allergic reaction have been seen in people taking RINVOQ. Some of these reactions were serious. If any of these symptoms occur during treatment with RINVOQ, stop taking RINVOQ and get emergency medical help right away.
• Tears in the stomach or intestines and changes in certain laboratory tests. Your HCP should do blood tests before you start taking RINVOQ and while you take it. Your HCP may stop your RINVOQ treatment for a period of time if needed because of changes in these blood test results.

Do not take RINVOQ if:

• You are allergic to upadacitinib or any of the ingredients in RINVOQ.

What should I tell my HCP BEFORE starting RINVOQ?

Tell your HCP if you:

• Are being treated for an infection, have an infection that won't go away or keeps coming back, or have symptoms of an infection, such as:

• Have TB or have been in close contact with someone with TB.
• Are a current or past smoker.
• Have had a heart attack, other heart problems, or stroke.
• Have or have had any type of cancer, hepatitis B or C, shingles (herpes zoster), blood clots in the veins of your legs or lungs, diverticulitis (inflammation in parts of the large intestine), or ulcers in your stomach or intestines.
• Have other medical conditions, including liver problems, low blood cell counts, diabetes, chronic lung disease, HIV, or a weak immune system.
• Live, have lived, or have traveled to parts of the country, such as the Ohio and Mississippi River valleys and the Southwest, that increase your risk of getting certain kinds of fungal infections. If you are unsure if you've been to these types of areas, ask your HCP.
• Have recently received or are scheduled to receive a vaccine. People who take RINVOQ should not receive live vaccines.
• Are pregnant or plan to become pregnant. Based on animal studies, RINVOQ may harm your unborn baby. Your HCP will check whether or not you are pregnant before you start RINVOQ. You should use effective birth control (contraception) to avoid becoming pregnant during treatment with RINVOQ and for 4 weeks after your last dose.
• Are breastfeeding or plan to breastfeed. RINVOQ may pass into your breast milk. Do not breastfeed during treatment with RINVOQ and for 6 days after your last dose.

Tell your HCP about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RINVOQ and other medicines may affect each other, causing side effects.

Especially tell your HCP if you take:

• Medicines for fungal or bacterial infections
• Rifampicin or phenytoin
• Medicines that affect your immune system

If you are not sure if you are taking any of these medicines, ask your HCP or pharmacist.

What should I avoid while taking RINVOQ?

Avoid food or drink containing grapefruit during treatment with RINVOQ as it may increase the risk of side effects.

What should I do or tell my HCP AFTER starting RINVOQ?

• Tell your HCP right away if you have any symptoms of an infection. RINVOQ can make you more likely to get infections or make any infections you have worse.
• Get emergency help right away if you have any symptoms of a heart attack or stroke while taking RINVOQ, including:
• Discomfort in the center of your chest that lasts for more than a few minutes or that goes away and comes back
• Severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw
• Pain or discomfort in your arms, back, neck, jaw, or stomach
• Shortness of breath with or without chest discomfort
• Breaking out in a cold sweat
• Nausea or vomiting
• Feeling lightheaded
• Weakness in one part or on one side of your body
• Slurred speech
• Tell your HCP right away if you have any signs or symptoms of blood clots during treatment with RINVOQ, including:

• Tell your HCP right away if you have a fever or stomach-area pain that does not go away, and a change in your bowel habits.

What are other possible side effects of RINVOQ?

Common side effects include upper respiratory tract infections (common cold, sinus infections), shingles (herpes zoster), herpes simplex virus infections (including cold sores), bronchitis, nausea, cough, fever, acne, headache, increased blood levels of creatine phosphokinase, allergic reactions, inflammation of hair follicles, stomach-area (abdominal) pain, increased weight, flu, tiredness, lower number of certain types of white blood cells (neutropenia, lymphopenia), muscle pain, flu-like illness, rash, increased blood cholesterol levels, and increased liver enzyme levels.

A separation or tear to the lining of the back part of the eye (retinal detachment) has happened in people with atopic dermatitis treated with RINVOQ. Call your HCP right away if you have any sudden changes in your vision during treatment with RINVOQ.

These are not all the possible side effects of RINVOQ.

How should I take RINVOQ?

RINVOQ is taken once a day with or without food. Do not split, crush, or chew the tablet. Take RINVOQ exactly as your HCP tells you to use it. RINVOQ is available in 15 mg, 30 mg, and 45 mg extended-release tablets.

This is the most important information to know about RINVOQ. For more information, talk to your HCP.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

If you are having difficulty paying for your medicine, AbbVie may be able to help. Visit AbbVie.com/myAbbVieAssist to learn more.

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 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 our 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 2021 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.

1. A Study to Investigate the Safety and Efficacy of Elsubrutinib and Upadacitinib Given Alone or in Combination in Participants With Moderately to Severely Active Systemic Lupus Erythematosus (SLE) (SLEek). ClinicalTrials.gov. 2022. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03978520?term=M19-130&draw=2&rank=2 . Accessed March 2023 .
2. AbbVie. Data on File: ABVRRTI75671
3. Abbvie, Ltd. RINVOQ (upadacitinib) [highlights of prescribing information]. Accessed March 20, 2023 . https://www.rxabbvie.com/pdf/rinvoq_pi.pdf .
4. Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. The Lancet . 2022;399(10341):2113-2128. doi:10.1016/S0140-6736(22)00581-5.
5. Mease PJ, Lertratanakul A, Anderson JK, et al. Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2. Annals of the Rheumatic Diseases . 2021;80(3):312-320. doi:10.1136/annrheumdis-2020-218870.
6. Guttman-Yassky E, Teixeira HD, Simpson EL, et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. The Lancet . 2021;397(10290):2151-2168. doi:10.1016/S0140-6736(21)00588-2.
7. Van der Heijde D, Song IH, Pangan AL, et al. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial. Lancet . 2019;394(10214):2108-2117. doi:10.1016/S0140-6736(19)32534-6.
8. Catalina MD, Owen KA, Labonte AC, et al. The pathogenesis of systemic lupus erythematosus: Harnessing big data to understand the molecular basis of lupus. J Autoimmun. 2020 Jun;110:102359. doi: 10.1016/j.jaut.2019.102359. Epub 2019 Dec 2 . PMID: 31806421.
9. Mayo Clinic. Lupus - Symptoms & Causes. Available at: https://www.mayoclinic.org/diseases-conditions/lupus/symptoms-causes/syc-20365789 . Accessed on August 26, 2022 .
10. Feldman CH, Hiraki LT, Liu J, Fischer MA, Solomon DH, Alarcón GS, Winkelmayer WC, Costenbader KH. Epidemiology and sociodemographics of systemic lupus erythematosus and lupus nephritis among US adults with Medicaid coverage, 2000-2004. Arthritis Rheum. 2013 Mar;65(3):753-63. doi: 10.1002/art.37795. PMID: 23203603; PMCID: PMC3733212.
11. Myles J. Lewis , Ali S. Jawad , The effect of ethnicity and genetic ancestry on the epidemiology, clinical features and outcome of systemic lupus erythematosus, Rheumatology, Volume 56, Issue suppl_1, April 2017 , Pages i67–i77, https://doi.org/10.1093/rheumatology/kew399 .
12. A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants with Moderately to Severely Active Ulcerative Colitis . clinicaltrials.gov; 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT03653026 . Accessed August 26, 2022 .
13. A Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Participants with Moderately to Severely Active Ulcerative Colitis (UC) . clinicaltrials.gov; 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635 . Accessed August 26, 2022 .
14. A Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects with Takayasu Arteritis (TAK) (SELECT-TAK) . clinicaltrials.gov; 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT04161898 . Accessed August 26, 2022 .
15. A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants with Axial Spondyloarthritis . clinicaltrials.gov; 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373 . Accessed August 26, 2022 .
16. Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet . 2018;391(10139):2503-2512. doi:10.1016/S0140-6736(18)31115-2.
17. Cohen SB, van Vollenhoven RF, Winthrop KL, et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis . Published online October 28 , 2020:annrheumdis-2020-218510. doi:10.1136/annrheumdis-2020-218510.
18. A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants with Giant Cell Arteritis . clinicaltrials.gov; 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202 . Accessed August 26, 2022 .
19. A Maintenance and Long-Term Extension Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants with Crohn's Disease Who Completed the Studies M14-431 or M14-433 . clinicaltrials.gov; 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT03345823 . Accessed August 26, 2022 .

View original content: https://www.prnewswire.com/news-releases/abbvie-advances-upadacitinib-rinvoq-to-phase-3-clinical-trials-in-systemic-lupus-erythematosus-301779254.html

SOURCE AbbVie