RINVOQ™ (upadacitinib) Achieved Superiority Versus DUPIXENT® (dupilumab) For Primary and All Ranked Secondary Endpoints in Phase 3b Head-to-Head Study in Adults with Atopic Dermatitis

- 71 percent of patients treated with upadacitinib achieved the primary endpoint of EASI 75 compared to 61 percent of patients treated with dupilumab at week 16 (p=0.006)[1]

- Upadacitinib showed superiority versus dupilumab for all ranked secondary endpoints, including early improvements in itch and skin clearance[1]

- The Heads Up study evaluated upadacitinib (30 mg, once daily) versus dupilumab (300 mg, every other week) in adults with moderate to severe atopic dermatitis[1]

- The safety profile of upadacitinib was consistent with previous atopic dermatitis studies, with no new safety risks observed[1-3]

- Upadacitinib, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is being studied as a once-daily oral therapy for moderate to severe atopic dermatitis and in several other immune-mediated diseases[1-11]

- Atopic dermatitis is a chronic, relapsing inflammatory condition affecting an estimated 10 percent of adults and 25 percent of adolescents[12-15]

News provided by

AbbVie

Dec 10, 2020, 08:45 ET

NORTH CHICAGO, Ill., Dec. 10, 2020 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced top-line results from the Phase 3b Heads Up study showing that upadacitinib (30 mg, once daily) achieved superiority to dupilumab (300 mg, every other week) for the primary endpoint, the proportion of patients with at least a 75 percent improvement in the Eczema Area Severity Index (EASI 75) at week 16, in adults with moderate to severe atopic dermatitis.¹ Of patients treated with upadacitinib, 71 percent achieved EASI 75 at week 16 compared to 61 percent of dupilumab-treated patients (p=0.006).¹ Upadacitinib also showed superiority compared to dupilumab for all ranked secondary endpoints, including additional measures of skin clearance and itch reduction.¹

The Heads Up study evaluated the efficacy and safety of upadacitinib versus dupilumab in adults with moderate to severe atopic dermatitis who are candidates for systemic therapy.¹ Patients were randomized to receive upadacitinib or dupilumab, both as monotherapy treatments, for 24 weeks.¹

"As we enter a new era of advanced therapies in atopic dermatitis, head-to-head studies like this will be important to help healthcare providers understand differences in therapies," said Michael Severino, M.D., vice chairman and president, AbbVie. "These results add to our growing body of evidence for RINVOQ in atopic dermatitis, which is currently under review by health authorities."

Results of ranked secondary endpoints showed higher efficacy in early improvements of itch and skin clearance in patients treated with upadacitinib compared to patients treated with dupilumab.¹After one week of treatment, the upadacitinib treatment group had a 31 percent reduction in itch (as measured by Worst Pruritus Numerical Rating Scale [NRS]) compared to 9 percent in the dupilumab group (p<0.001).¹Itch improvements were maintained through week 16.¹ Additionally, after two weeks of treatment, 44 percent of upadacitinib-treated patients achieved EASI 75 response versus 18 percent of dupilumab-treated patients (p<0.001).¹

Heads Up Results at Week 16*^,1
	Dupilumab (300 mg) (n=344)	Upadacitinib (30 mg) (n=348)
EASI 75^a	61%	71%
EASI 90^b	39%	61%
EASI 100^c	8%	28%
Percent Change from Baseline in Worst Pruritus NRS^d	-49%	-67%
Worst Pruritus NRS Improvement ≥4^e (Dupilumab, n=336) (Upadacitinib, n=340)	36%	55%

* Primary endpoint was EASI 75 at week 16. Primary endpoint achieved a p-value of 0.006. EASI 90 and EASI 100 at week 16, percent change from baseline in Worst Pruritus NRS at week 16 and improvement in Worst Pruritus NRS ≥4 at week 16 were ranked secondary endpoints. All ranked secondary endpoints achieved p-values of <0.001. Not all ranked secondary endpoints are shown.

^a EASI 75 is defined as at least a 75 percent reduction in Eczema Area and Severity Index.

^b EASI 90 is defined as at least a 90 percent reduction in Eczema Area and Severity Index.

^c EASI 100 is defined as a complete reduction in Eczema Area and Severity Index.

^d Defined as percent change from baseline in Worst Pruritus Numerical Rating Scale [NRS].

^e Worst Pruritus NRS improvement ≥4 is defined as an improvement (reduction) in Worst Pruritus NRS ≥4. The endpoint was analyzed for participants with pruritus NRS ≥4 at baseline.

The safety profile of upadacitinib was consistent with what was observed in the Phase 3 pivotal studies, Measure Up 1, Measure Up 2 and AD Up.^1-3 Through week 16, the most common adverse events were acne for the upadacitinib group and conjunctivitis for the dupilumab group.¹ Serious adverse events occurred in 2.9 percent of patients receiving upadacitinib and 1.2 percent of patients receiving dupilumab.¹ Serious infections were reported infrequently in both treatment groups (1.1 percent in patients who received upadacitinib and 0.6 percent in patients who received dupilumab).¹ One treatment-emergent death due to bronchopneumonia associated with influenza A occurred in a patient who received upadacitinib.¹ No malignancies were reported in the upadacitinib group; one non-melanoma skin cancer was reported in the dupilumab group.¹ No major adverse cardiac events or venous thromboembolic events were reported in either treatment group.¹

Full results from the Heads Up study will be submitted for publication in a peer-reviewed journal. Use of RINVOQ in atopic dermatitis is not approved and its safety and efficacy are under evaluation by regulatory authorities.

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.^12,13It affects up to an estimated 10 percent of adults and 25 percent of adolescents.^13,14 Between 20 and 46 percent of adults with atopic dermatitis have moderate to severe disease.¹⁵ The range of symptoms pose significant physical, psychological and economic burden on individuals impacted by the disease.^13,16

About Heads Up¹

Heads Up is a Phase 3b multicenter, randomized, double-blind, double-dummy, active comparator-controlled study in adults with moderate to severe atopic dermatitis. Patients were randomized to receive upadacitinib (30 mg, once daily, orally administered) or dupilumab (300 mg, every other week, subcutaneous injection) for 24 weeks. Patients who received dupilumab received an initial dose of 600 mg at the baseline visit followed by 300 mg every other week. All patients received placebo of the other arm's administration as part of the Heads Up double-dummy study design.

The primary endpoint was the proportion of patients achieving EASI 75 at week 16. Ranked secondary endpoints included EASI 75 at week 2, percent change from baseline in Worst Pruritus NRS at week 1 and week 16, EASI 90 at week 16, EASI 100 at week 16 and improvement in Worst Pruritus NRS ≥4 at week 16. More information on this trial can be found at www.clinicaltrials.gov (NCT03738397).

About RINVOQ™ (upadacitinib)

Discovered and developed by AbbVie scientists, RINVOQ is an oral, once daily, selective and reversible JAK inhibitor studied in several immune-mediated inflammatory diseases.^1-11It was engineered to have greater inhibitory potency for JAK1 versus JAK2, JAK3 and TYK2.¹⁷ In August 2019, RINVOQ received U.S. Food and Drug Administration approval for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. In December 2019, RINVOQ also received approval by the European Commission for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs. The approved dose for RINVOQ in rheumatoid arthritis is 15 mg. Phase 3 trials of RINVOQ in atopic dermatitis, rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing.^1,5-11Use of RINVOQ in atopic dermatitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

Important Safety Information about RINVOQ™ (upadacitinib)¹⁸

RINVOQ U.S. Use and Important Safety Information
RINVOQ is a prescription medicine used to treat adults with moderate to severe rheumatoid arthritis in whom methotrexate did not work well or could not be tolerated. It is not known if RINVOQ is safe and effective in children under 18 years of age.

What is the most important information I should know about RINVOQ?
RINVOQ is a medicine that can lower the ability of your immune system to fight infections. You should not start taking RINVOQ if you have any kind of infection unless your healthcare provider (HCP) tells you it is okay.

Serious infections have happened in some people 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 HCP should test you for TB before starting RINVOQ and check you closely for signs and symptoms of TB during treatment with RINVOQ. You may be at higher risk of developing shingles (herpes zoster).
Lymphoma and other cancers, including skin cancers, can happen in people taking RINVOQ.
Blood clots in the veins of the legs or lungs and arteries are possible in some people taking RINVOQ. This may be life-threatening and cause death.
Tears in the stomach or intestines and changes in certain laboratory tests can happen. 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.

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.
Have had any type of cancer, hepatitis B or C, shingles (herpes zoster), or 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 that increase your risk of getting certain kinds of fungal infections, such as the Ohio and Mississippi River valleys and the Southwest. If you are unsure if you've been to these 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 while taking RINVOQ and for at least 4 weeks after your last dose.
Are breastfeeding or plan to breastfeed. RINVOQ may pass into your breast milk. You should not breastfeed while taking RINVOQ and for at least 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

Ask your HCP or pharmacist if you are not sure if you are taking any of these medicines.

What should I 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.
Have any signs or symptoms of blood clots during treatment with RINVOQ, including:

Swelling
Sudden unexplained chest pain
Pain or tenderness in the leg
Shortness of breath

Have a fever or stomach-area pain that does not go away, and a change in your bowel habits.

What are the common side effects of RINVOQ?
These include: upper respiratory tract infections (common cold, sinus infections), nausea, cough, and fever. These are not all the possible side effects of RINVOQ.

RINVOQ is taken once a day with or without food. Do not split, break, crush, or chew the tablet. Take RINVOQ exactly as your HCP tells you to use it.

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 http://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 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, Instagram, YouTube and LinkedIn.

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 2019 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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