RINVOQ™ (upadacitinib) Monotherapy Meets All Primary and Secondary Endpoints in Second Phase 3 Study for Atopic Dermatitis

- Upadacitinib (15 mg and 30 mg) monotherapy showed significant improvement in skin clearance and reduction in itch at week 16 in adult and adolescent patients with moderate to severe atopic dermatitis versus placebo[1]

- Safety results were consistent with those of its replicate study, Measure Up 1[2]

- RINVOQ, 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[1,3-10]

News provided by

AbbVie

Jul 21, 2020, 08:45 ET

NORTH CHICAGO, Ill., July 21, 2020 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced upadacitinib (15 mg and 30 mg, once daily) monotherapy met both primary and all secondary endpoints in Measure Up 2, the second Phase 3 study in individuals with moderate to severe atopic dermatitis.¹ The co-primary endpoints were at least a 75 percent improvement in the Eczema Area Severity Index (EASI 75) from baseline and a validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1 (clear or almost clear) at week 16.¹The Measure Up 2 study evaluates the efficacy and safety of both doses of upadacitinib monotherapy versus placebo in adolescents and adults with moderate to severe atopic dermatitis who are candidates for systemic therapy.¹

Significantly more patients receiving either dose of upadacitinib monotherapy showed improvement in skin clearance and reduction in itch compared to placebo at week 16.¹ In the study, 60/73 percent of patients receiving upadacitinib 15/30 mg achieved EASI 75, respectively, versus 13 percent in the placebo group (p<0.001).¹Of patients treated with upadacitinib 15/30 mg, 39/52 percent achieved vIGA-AD 0/1, respectively, versus 5 percent of patients receiving placebo (p<0.001).¹

"We are encouraged by these results that reaffirm the data from Measure Up 1 and underscore the potential impact RINVOQ could have for individuals struggling to control their atopic dermatitis," said Michael Severino, M.D., vice chairman and president, AbbVie. "We are committed to delivering on the needs of people living with atopic dermatitis, many of whom continue to endure relentless itch and skin symptoms that can interfere with daily activities."

At week 16, 42/60 percent of patients on upadacitinib 15/30 mg experienced clinically meaningful reductions in itch, respectively, defined as improvement in Worst Pruritus Numerical Rating Scale (NRS) ≥4, versus 9 percent of patients receiving placebo (p<0.001).¹For both doses, patients experienced an early reduction in itch, which was maintained through week 16.¹ After just one day following the first dose (day 2), reductions in itch compared to placebo were observed for patients receiving upadacitinib 30 mg (8 percent versus 1 percent, p<0.001).¹ For patients receiving upadacitinib 15 mg, 12 percent experienced a reduction in itch after just two days following the first dose (day 3) compared to 3 percent of patients receiving placebo (p<0.001).¹

"Atopic dermatitis is more than a rash or itchy skin. Many people living with moderate to severe forms continue to suffer from significant physical and emotional burden of the disease," said Alan Irvine, M.D., D.S.c., professor of dermatology, Trinity College Dublin, Ireland and lead study investigator of Measure Up 2. "These data support our continued efforts to provide additional options for those living with moderate to severe atopic dermatitis."

*Measure Up 2 Results at Week 16^,1**
	Upadacitinib 15 mg (n=276)	Upadacitinib 30 mg (n=282)	Placebo (n=278)
EASI 75^a	60%	73%	13%
vIGA-AD 0/1^b	39%	52%	5%
Improvement in Worst Pruritus NRS≥4^c	42%	60%	9%

* Co-primary endpoints were EASI 75 and vIGA-AD 0/1 at week 16. Co-primary endpoints achieved p-values of <0.001. Improvement in Worst Pruritus NRS≥4 at day 2 (upadacitinib 30 mg), day 3 (upadacitinib 15 mg) and week 16 were secondary endpoints. All secondary endpoints achieved p-values of <0.001. Not all secondary endpoints are shown.

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

^b vIGA-AD 0/1 is defined as a validated Investigator Global Assessment for Atopic Dermatitis of clear or almost clear (0/1) with at least two grades of reduction from baseline.

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

Atopic dermatitis is a chronic, relapsing inflammatory condition characterized by a cycle of intense itching and scratching leading to cracked, scaly, oozing skin.^11,12It affects up to an estimated 25 percent of adolescents and 10 percent of adults at some point in their lifetime.¹² Between 20 and 46 percent of adults with atopic dermatitis have moderate to severe disease.¹³ The range of symptoms pose significant physical, psychological and economic burden on individuals impacted by the disease.^12,14

No new safety risks were observed compared to the safety profile observed in patients with rheumatoid arthritis and psoriatic arthritis receiving RINVOQ.^1,15-18 During the 16-week placebo-controlled period of Measure Up 2, serious adverse events (SAEs) occurred in 1.8 percent of patients in the upadacitinib 15 mg and 2.5 percent of patients in the upadacitinib 30 mg compared to 2.9 percent of patients in the placebo group.¹The most common AEs for the upadacitinib groups were acne, headache and upper respiratory tract infection.¹ Acne was observed with both doses of upadacitinib (12.7 percent of patients on 15 mg and 14.5 percent of patients on 30 mg) versus placebo (2.2 percent of patients); all events were mild or moderate in severity and none led to treatment discontinuation.¹ Eczema herpeticum was only observed in patients receiving upadacitinib 15 mg (1.1 percent of patients).¹ Serious infections were reported infrequently (0.7 percent of patients receiving upadacitinib 30 mg, 0.4 percent of patients receiving upadacitinib 15 mg and 0.7 percent of patients receiving placebo).¹ No venous thromboembolic events (VTEs) were observed in the upadacitinib groups; a pulmonary embolism was reported in a patient receiving placebo.¹ No deaths or major adverse cardiac events (MACE) were reported in any of the treatment groups.¹

Full results from the Measure Up 2 study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal. Use of RINVOQ in atopic dermatitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

About Measure Up 2 Study^1,10

Measure Up 2 is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib in adults and adolescents (ages 12 to 18 or older) with moderate to severe atopic dermatitis who are candidates for systemic treatment. Patients were randomized to upadacitinib 15 mg, upadacitinib 30 mg or placebo. Placebo patients were switched to either upadacitinib 15 mg or upadacitinib 30 mg at week 16.

The co-primary endpoints were the percentage of patients achieving EASI 75 and a vIGA-AD of 0/1 after 16 weeks of treatment. Secondary endpoints included improvement in Worst Pruritus NRS≥4, EASI 90, percent change in Worst Pruritus NRS, percent change in EASI at week 16, as well as improvement in Worst Pruritus NRS≥4 at day 2 (one day after the first dose) for patients receiving upadacitinib 30 mg and improvement in Worst Pruritus NRS≥4 at day 3 (two days after the first dose) for patients receiving upadacitinib 15 mg. The trial is ongoing, and the long-term extension period remains blinded to investigators and patients, to evaluate the long-term safety, tolerability and efficacy of the two once-daily doses (15 mg and 30 mg) of upadacitinib in patients who have completed the placebo-controlled period. Top-line results from the replicate Phase 3 study, Measure Up 1, were announced in June 2020.

More information on this trial can be found at www.clinicaltrials.gov (NCT03607422).

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.^1,3-10 It was engineered to have greater inhibitory potency for JAK1 versus JAK2, JAK3 and TYK2.¹⁵ 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 and giant cell arteritis are ongoing.^5-10Use 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)

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 in Dermatology

For more than a decade, AbbVie has worked to uncover new solutions and improve care for people with serious skin diseases, including psoriasis, psoriatic arthritis, hidradenitis suppurativa and atopic dermatitis. With a broad clinical trial program, we continue to actively research and adapt to the evolving needs of the dermatology community and advance our pipeline to help people achieve their treatment goals and live beyond their skin disease. For more information on AbbVie in dermatology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/dermatology.html.

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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