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]

NORTH CHICAGO, IL, USA I July 21, 2020 I 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 16.¹ The 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).¹ Of 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).¹ For 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 75a	60%	73%	13%
vIGA-AD 0/1b	39%	52%	5%
Improvement in Worst Pruritus NRS≥4c	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.^11,12 It 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.¹ The 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.^5-10 Use of RINVOQ in atopic dermatitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

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.

References:

1. AbbVie Data on File. ABVRRTI70838.
2. AbbVie Data on File. ABVRRTI70713.
3. Pipeline – Our Science | AbbVie. AbbVie. 2019. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on July 16, 2020.
4. Burmester G.R., 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 Jun 23;391(10139):2503-2512. doi: 10.1016/S0140-6736(18)31115-2. Epub 2018 Jun 18.
5. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of ABT-494 for the Induction of Symptomatic and Endoscopic Remission in Subjects With Moderately to Severely Active Crohn’s Disease Who Have Inadequately Responded to or Are Intolerant to Immunomodulators or Anti-TNF Therapy. ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed on July 16, 2020.
6. A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Participants With Psoriatic Arthritis Who Have an Inadequate Response to at Least One Non-Biologic Disease Modifying Anti-Rheumatic Drug (SELECT – PsA 1). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed on July 16, 2020.
7. A Study to Evaluate the Safety and Efficacy of ABT-494 for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis. ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed on July 16, 2020.
8. A Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis (SELECT Axis 1). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/study/NCT03178487. Accessed on July 16, 2020.
9. A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed on July 16, 2020.
10. A Study to Evaluate Upadacitinib in Adolescent and Adult Subjects With Moderate to Severe Atopic Dermatitis. ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/record/NCT03607422. Accessed on July 16, 2020.
11. Nutten S. Atopic Dermatitis: Global Epidemiology and Risk Factors. Ann Nutr Metab 2015;66(suppl 1):8–16.
12. Weidinger, S., et al. Atopic dermatitis. Nat Rev Dis Primers 4, 1 (2018). https://doi.org/10.1038/s41572-018-0001-z.
13. Shrestha S et al. Burden of Atopic Dermatitis in the United States: Analysis of Healthcare Claims Data in the Commercial, Medicare, and Medi-Cal Databases. Adv Ther. 2017;34(8):1989–2006.
14. EFA. Atopic Eczema: Itching for Life Report. 2018. Available at: https://www.efanet.org/images/2018/EN_-_Itching_for_life_Quality_of_Life_and_costs_for_people_with_severe_atopic_eczema_in_Europe_.pdf. Accessed on July 16, 2020.
15. Cohen S., et al. Safety profile of upadacitinib in Rheumatoid Arthritis: Integrated analysis from the SELECT Phase 3 Clinical Program. EULAR 2019; THU0167.
16. Guttman-Yassky, E et al. ePoster #P0236. 27th European Academy of Dermatology and Venerology (EADV) Congress. September 2018.
17. Genovese MC, et al. Efficacy and Safety of Upadacitinib in Patients With Active Psoriatic Arthritis and Inadequate Response to Biologic Disease-Modifying Anti-Rheumatic Drugs (SELECT-PsA-2): a Double-Blind, Randomized Controlled Phase 3 Trial. 2020 EULAR E-Congress; OP0223.
18. McInnes I, et al. Efficacy and Safety of Upadacitinib Versus Placebo and Adalimumab in Patients With Active Psoriatic Arthritis and Inadequate Response to Non-Biologic Disease-Modifying Anti-Rheumatic Drugs (SELECT-PsA-1): a Double-Blind, Randomized Controlled Phase 3 Trial. 2020 EULAR E-Congress; LB0001.

SOURCE: AbbVie