ABBV AbbVie Inc

• Upadacitinib demonstrated superiority versus dupilumab in primary endpoint of simultaneous achievement of near complete skin clearance (EASI 90) and no to little itch (WP-NRS 0/1) at Week 16¹
• LEVEL UP, a Phase 3b/4 head-to-head study, compared upadacitinib to dupilumab for the treatment of adult and adolescent patients with moderate-to-severe atopic dermatitis who had inadequate response to systemic therapy or when use of those therapies was inadvisable¹
• The safety profile of upadacitinib was consistent with the profile in previous atopic dermatitis studies with no new safety signals identified during the 16-week period^1,2

NORTH CHICAGO, Ill., April 25, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced positive topline results from LEVEL UP, an open-label, efficacy assessor-blinded head-to-head Phase 3b/4 study that evaluated the efficacy and safety of upadacitinib (RINVOQ^®, 15 mg once daily starting dose and dose-adjusted based on clinical response) versus dupilumab (DUPIXENT^®, per its labeled dose) in adults and adolescents (≥12 years of age) with moderate-to-severe atopic dermatitis (AD) who had an inadequate response to systemic therapy or when use of those therapies was inadvisable.

"Even while receiving conventional treatments, many patients with atopic dermatitis still continue to live with significant itch and inflammatory skin symptoms that can profoundly impact their everyday lives," said Roopal Thakkar, M.D., senior vice president, chief medical officer, global therapeutics, AbbVie. "Results from this study show that patients with moderate-to-severe atopic dermatitis can strive for both little to no itch and clearer skin."

In the LEVEL UP study, upadacitinib showed superior efficacy versus dupilumab in the primary endpoint, demonstrating that a significantly higher proportion of patients simultaneously achieved both a 90% or greater reduction in Eczema Area and Severity Index (EASI 90) and a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 16 [(19.9% vs 8.9% for upadacitinib and dupilumab respectively, p<0.0001)].¹

The EASI is a clinically validated measure used to assess the severity and extent of atopic dermatitis, while the WP-NRS is an assessment tool that patients use to report the intensity of their pruritus daily (with 0 being 'no itch' and 10 being the 'worst imaginable itch').

Upadacitinib also showed superiority versus dupilumab for all ranked secondary endpoints, including the rapid onset of achieving near complete skin clearance and no to little itch. For the first two ranked secondary endpoints, the study showed that a significantly higher proportion of patients treated with upadacitinib:

• Achieved EASI 90 at Week 16 [(40.8% vs 22.5%, p<0.0001)].¹
• Achieved a WP-NRS of 0/1 at Week 16 [(30.2% vs 15.5%, p<0.0001)].^1,a

AbbVie plans to present results from the LEVEL UP study at a future medical congress.

The LEVEL UP study is the first head-to-head trial in atopic dermatitis assessing upadacitinib at a starting dose of 15 mg daily versus dupilumab at its labeled dose. Upadacitinib was initiated in adults and adolescents (≥12 years of age, weighing at least 40 kg) at 15 mg once daily (QD) and dose-escalated to 30 mg QD based on clinical response. Dupilumab was initiated at 600 mg, followed by 300 mg every other week (Q2W) in adults and adolescents weighing ≥60 kg; adolescents weighing less than 60 kg received an initial dose of 400 mg, followed by 200 mg Q2W.¹

"Too many patients are still not achieving optimal disease control in atopic dermatitis despite taking steps to manage their condition," said Jonathan Silverberg, M.D., Ph.D., MPH, professor of dermatology and director of clinical research at the George Washington University School of Medicine and Health Sciences. "Results from the LEVEL UP study highlight how treatment options such as upadacitinib can achieve high treatment goals in atopic dermatitis with combined measures of EASI 90 and NRS 0/1, not just itch resolution or just skin clearance."

The observed safety profile for upadacitinib in LEVEL UP was consistent with that observed in previous upadacitinib atopic dermatitis clinical studies.^1,2 No new safety signals were identified during the study period.¹ In Period 1, the most common adverse events (AE) reported were nasopharyngitis for both the upadacitinib and dupilumab group.¹ The rate of serious AEs (0.9%) was the same for both upadacitinib and dupilumab. There was one serious infection reported in the dupilumab group and none in the upadacitinib group.¹ No malignancies, adjudicated major adverse cardiac events, adjudicated venous thromboembolic events (VTEs) or treatment-emergent deaths were reported in either treatment group.¹

^[a] This endpoint was evaluated among patients with a baseline WP-NRS >1.

About Atopic Dermatitis 
Atopic dermatitis is a chronic, relapsing inflammatory condition characterized by a cycle of intense itching and scratching leading to cracked, scaly, oozing skin.^3,4 It affects up to an estimated 10% of adults and 24.6% of adolescents.^4-6 Between 20% and 46% of adults with atopic dermatitis have moderate-to-severe disease.⁷ The range of symptoms poses significant physical, psychological and economic burden on individuals impacted by the disease.^4,8

About LEVEL UP 
LEVEL UP is a Phase 3b/4, multi-center, randomized, open-label, efficacy assessor-blinded study, comparing the efficacy and safety of upadacitinib versus dupilumab in adult and adolescent (≥12 years of age, weighing at least 40 kg) patients with moderate-to-severe atopic dermatitis who had inadequate response to systemic therapy or when use of those therapies was inadvisable. The study comprises a 35-day screening period, a 16-week treatment Period 1 and a 16-week treatment Period 2. During Period 1, participants were randomly assigned in one of two groups to receive upadacitinib 15 mg QD or dupilumab as per its label. In Period 2, participants received upadacitinib as per protocol-defined criteria. The primary endpoint was the simultaneous achievement of a 90% or greater reduction in Eczema Area and Severity Index (EASI 90) and a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 16. Key ranked secondary endpoints included the achievement of EASI 90 at Week 16, and the achievement of a WP-NRS of 0/1 at Week 16 among those with a Baseline WP-NRS >1. The mean body surface area (BSA) among patients enrolled in the study was 38%, and 42% of patients had severe disease (vIGA-AD = 4) at baseline. More information on this trial can be found at https://www.clinicaltrials.gov/ (NCT05601882).

About RINVOQ^® (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK-1 vs JAK-2, JAK-3, and TYK-2.² The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known.

Clinical trials of RINVOQ are ongoing in alopecia areata, ankylosing spondylitis, atopic dermatitis, axial spondyloarthritis, Crohn's disease, giant cell arteritis, hidradenitis suppurativa, psoriatic arthritis, rheumatoid arthritis, systemic lupus erythematosus (SLE), Takayasu arteritis, ulcerative colitis and vitiligo.^9-22

RINVOQ (upadacitinib) U.S. Uses and Important Safety Information²

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 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.
• 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 moderate to severe Crohn's disease (CD) when 1 or more medicines called TNF blockers have 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, ankylosing spondylitis, non-radiographic axial spondyloarthritis, ulcerative colitis, or Crohn's disease.

• 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.

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. This happens most often in people who take nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids. Get medical help right away if you get stomach-area pain, fever, chills, nausea, or vomiting.
• 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. See the Medication Guide or Consumer Brief Summary for a complete list of ingredients.

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:
  • Fever, sweating, or chills
  • Shortness of breath
  • Warm, red, or painful skin or sores on your body
  • Muscle aches
  • Feeling tired
  • Blood in phlegm
  • Diarrhea or stomach pain
  • Cough
  • Weight loss
  • Burning when urinating or urinating more often than normal
• 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 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 red or white 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 findings in 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.
• There is a pregnancy surveillance program for RINVOQ. The purpose of the program is to collect information about the health of you and your baby. If you become pregnant while taking RINVOQ, you are encouraged to report the pregnancy by calling 1-800-633-9110.
• 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:
  • Swelling
  • Pain or tenderness in one or both legs
  • Sudden unexplained chest or upper back pain
  • Shortness of breath or difficulty breathing
• 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, leukopenia), muscle pain, flu-like illness, rash, increased blood cholesterol levels,  increased liver enzyme levels, pneumonia, low number of red blood cells (anemia), and infection of the stomach and intestine (gastroenteritis).

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.

Some people taking RINVOQ may see medicine residue (a whole tablet or tablet pieces) in their stool. If this happens, call your healthcare provider.

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. 

Please click here for the Full Prescribing Information and Medication Guide.

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 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 2023 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.

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