New Long-term Data from RINVOQ® ▼(upadacitinib). Phase 3 Studies in Rheumatoid Arthritis Presented at Annual European E-Congress of Rheumatology (EULAR)

• Long-term results from the SELECT-COMPARE and SELECT-MONOTHERAPY studies showed that upadacitinib continued to improve signs and symptoms in patients with rheumatoid arthritis through 72 and 84 weeks, respectively^1,2
• Results from SELECT-EARLY and SELECT-COMPARE showed upadacitinib inhibited structural joint damage in rheumatoid arthritis patients receiving upadacitinib as monotherapy or in combination with MTX at almost two years³
• Upadacitinib’s safety profile was consistent across the pivotal Phase 3 programme, with no new safety signals identified^1-5

MAIDENHEAD, UK, June 8, 2020– AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced new long-term results showing that once-daily RINVOQ^®(upadacitinib) continued to improve signs and symptoms in patients with rheumatoid arthritis at 72 and 84 weeks in the SELECT-COMPARE (15 mg in combination with methotrexate [MTX]) and SELECT-MONOTHERAPY (15 mg and 30 mg) Phase 3 clinical trials, respectively.^1,2The safety profile of upadacitinib (15 mg and 30 mg) monotherapy or upadacitinib (15 mg) in combination with MTX was consistent with that observed in the previously reported integrated Phase 3 safety analysis in rheumatoid arthritis, with no new safety risks detected.

Additionally, approximate two-year data (96 weeks) from the SELECT-EARLY and SELECT-COMPARE clinical trials showed that upadacitinib was effective in inhibiting structural joint damage in patients receiving upadacitinib as monotherapy or in combination with MTX.³ Full results were presented today at the 2020 Annual European E-Congress of Rheumatology (EULAR).

Upadacitinib, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is approved as an oral, once-daily, 15 mg therapy for adults with moderate to severe active rheumatoid arthritis ^1-5.

“These new long-term data showcase the potential of upadacitinib to provide relief from the signs and symptoms of rheumatoid arthritis, both as a monotherapy and in combination with methotrexate,” said Isidro Villanueva, vice president, medical affairs immunology, AbbVie. “We are excited to share these results with the rheumatology community reinforcing upadacitinib as an important treatment option that may help more patients living with rheumatoid arthritis reach their goals in disease management.”

SELECT-COMPARE Results at 72 Weeks

Results of this Long-Term Extension (LTE) of the SELECT-COMPARE study show that upadacitinib plus MTX maintained higher levels of clinical response, including remission compared to adalimumab plus MTX through week 72.

^{*Efficacy data reported based on randomised treatment. For patients who were rescued, non-responder imputation (NRI) was used for binary endpoints. All reported endpoints achieved p-values of ≤0.001 for upadacitinib plus MTX versus adalimumab plus MTX through week 72, except for ACR20 at week 72 (p≤0.01).}

^{† Patients who received adalimumab were switched to receive 15 mg of upadacitinib, and vice versa if they did not achieve at least a 20 percent improvement in both tender and swollen joint count at weeks 14, 18 or 22, or if Clinical Disease Activity Index (CDAI) was greater than 10 at week 26. Non-responder imputation (NRI) was used for rescue prior to Week 26 and last observation carried forward (LOCF) was used for rescue at Week 26.}

^{aACR20/50/70 is defined as at least a 20 percent/50 percent/70 percent reduction from baseline in the number of both tender and swollen joint counts and equivalent improvement in three or more of the five remaining American College of Rheumatology core set measures: patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant.}

^{bClinical remission is defined as Disease Activity Score with 28 joint counts C-reactive protein (DAS28-CRP) less than 2.6.}

^{cLow disease activity (LDA) is defined as Disease Activity Score with 28 joint counts C-reactive protein (DAS28-CRP) less than or equal to 3.2.}

The safety profile of upadacitinib (15 mg) in combination with MTX was generally consistent with that observed in the previously reported integrated Phase 3 safety analysis in rheumatoid arthritis, with no new safety risks detected.¹ Through the data cut-off, serious adverse events occurred at 12.7 events/100PY (per 100 patient years) on upadacitinib 15 mg in combination with MTX, compared to 15.9 events/100PY on adalimumab in combination with MTX.^1,4 The rate of serious infections was 3.7 events/100PY on upadacitinib 15 mg plus MTX and 4.3 events/100PY on adalimumab plus MTX.¹ There were eight deaths on upadacitinib (0.6/100PY) and six deaths on adalimumab (1.2/100PY), including non-treatment emergent deaths.¹ There were eight major adverse cardiac events (MACE) through the study duration, including five on upadacitinib (0.4/100PY) and three on adalimumab (0.6/100PY).¹ There were four patients with venous thromboembolism events (VTE) reported on upadacitinib (0.3/100PY) and five reported on adalimumab (1.0/100 PY).¹

The safety profile of upadacitinib (15 mg) in combination with MTX was generally consistent with that observed in the previously reported integrated Phase 3 safety analysis in rheumatoid arthritis, with no new safety risks detected.¹ Through the data cut-off, serious adverse events occurred at 12.7 events/100PY (per 100 patient years) on upadacitinib 15 mg in combination with MTX, compared to 15.9 events/100PY on adalimumab in combination with MTX.^1,4 The rate of serious infections was 3.7 events/100PY on upadacitinib 15 mg plus MTX and 4.3 events/100PY on adalimumab plus MTX.¹ There were eight deaths on upadacitinib (0.6/100PY) and six deaths on adalimumab (1.2/100PY), including non-treatment emergent deaths.¹ There were eight major adverse cardiac events (MACE) through the study duration, including five on upadacitinib (0.4/100PY) and three on adalimumab (0.6/100PY).¹ There were four patients with venous thromboembolism events (VTE) reported on upadacitinib (0.3/100PY) and five reported on adalimumab (1.0/100 PY).¹

SELECT-MONOTHERAPY Results at 84 Weeks

In this LTE of the SELECT-MONOTHERAPY study, patients who received continued MTX in the first phase of the study were switched to receive blinded upadacitinib 15 mg or 30 mg at week 14 based on pre-specified assignment at baseline.²Results of this LTE show that upadacitinib monotherapy resulted in continued improvements in rheumatoid arthritis signs and symptoms through 84 weeks.

^{*Results are based on AS Observed analyses; †Upadacitinib 30 mg is not an approved dose.; aACR20/50/70 is defined as at least a 20 percent/50 percent/70 percent reduction from baseline in the number of both tender and swollen joint counts and equivalent improvement in three or more of the five remaining American College of Rheumatology core set measures: patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant; bClinical remission is defined as Disease Activity Score with 28 joint counts C-reactive protein (DAS28-CRP) less than 2.6; cLow disease activity (LDA) is defined as Disease Activity Score with 28 joint counts C-reactive protein (DAS28-CRP) less than or equal to 3.2.}

The safety profile of upadacitinib (15 mg and 30 mg) monotherapy at week 84 was generally consistent with that observed in the previously reported integrated Phase 3 safety analysis in rheumatoid arthritis, with no new safety risks detected.² Through week 84, serious adverse events occurred at 18.5 events/100PY (per 100 patient years) on upadacitinib 15 mg and 16.9 events/100PY on upadacitinib 30 mg.² The most common serious adverse event was pneumonia.^2,4Events of herpes zoster, hepatic disorder and creatine phosphokinase elevations were higher among patients receiving upadacitinib 30 mg, while rates of serious infection and malignancy were comparable between upadacitinib 30 mg and 15 mg.² Seven patients experienced MACE (15 mg, 0.5/100 PY; 30 mg, 1.2/100 PY) and there were five VTE (15 mg, 0.9/100 PY; 30 mg, 0.2/100 PY).² All MACE and VTE events occurred in patients with underlying risk factors.²There were three deaths each (0.7/100PY) on upadacitinib 15 mg and 30 mg, including non-treatment emergent deaths.

Radiographic Inhibition at Approximately Two Years: SELECT-EARLY and SELECT-COMPARE

Both SELECT-EARLY and SELECT-COMPARE enrolled rheumatoid arthritis patients at high risk for progressive structural damage with baseline erosive joint damage and/or seropositivity.³

Upadacitinib inhibited structural joint damage in MTX naïve patients receiving upadacitinib monotherapy and in patients with an inadequate response to MTX in combination with MTX.³

^{* upadacitinib 30 mg is not an approved dose; d No radiographic progression is defined as a change in modified Total Sharp Score (mTSS)≤0}

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UK Media:

Natalie Bennett

AbbVie

T: 07818 428074
E: natalie.bennett@abbvie.com

Notes to Editors

About RINVOQ^® (upadacitinib) in the European Union⁵

Discovered and developed by AbbVie scientists, upadacitinib is a selective and reversible JAK inhibitor. In December 2019, upadacitinib was approved 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 upadacitinib in rheumatoid arthritis is 15mg.

Upadacitinib is currently undergoing review by the National Institute for Health and Care Excellence (NICE) for its the routine use across the NHS.

For full upadacitinib Summary of Product Characteristics visit: https://www.medicines.org.uk/emc/product/10972

Adverse events should be reported. ▼ This medicinal product is subject to additional monitoring and it is therefore important to report any suspected adverse events related to this medicinal product. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Adverse events should also be reported to AbbVie on UK_PVVendor@abbvie.com

About SELECT-COMPARE¹

SELECT-COMPARE is a Phase 3, multicenter, randomised, double-blind study designed to evaluate the safety and efficacy of upadacitinib compared to placebo and adalimumab in adult patients with moderate to severe active rheumatoid arthritis who had an inadequate response to methotrexate and continued a stable background of MTX. Patients received background MTX and were randomized 2:2:1 to receive upadacitinib (15 mg once-daily), placebo or adalimumab (given as a subcutaneous injection of 40 mg every other week).

The primary endpoints of the first phase included the percentage of subjects achieving ACR20 and clinical remission (based on DAS28-CRP) after 12 weeks of treatment compared to placebo. Ranked secondary endpoints included change in the mTSS compared to placebo and a comparison versus adalimumab in percentage of subjects achieving ACR50, low disease activity, changes in pain as measured by the Patient's Assessment of Pain (based on VAS) and changes in physical function, as measured by the HAQ-DI. The trial is ongoing and included a 48 week randomised, double-blind treatment period followed by a long-term extension study of up to five years. More information on this trial can be found at www.clinicaltrials.gov (NCT02629159).

About SELECT-MONOTHERAPY²

SELECT-MONOTHERAPY is a Phase 3, multicenter, randomized, double-blind, parallel-group study designed to evaluate the safety and efficacy of upadacitinib monotherapy in adult patients with moderate to severe active rheumatoid arthritis and an inadequate response to a stable dose of methotrexate. Patients were randomised to switch from MTX to upadacitinib monotherapy (15 mg or 30 mg once-daily) or continue on their prior stable dose of MTX in a blinded manner.

The primary endpoints of the first phase included the percentage of patients achieving an ACR20 response and low disease activity after 14 weeks of treatment. Secondary endpoints included proportion of patients achieving ACR50, ACR70 and clinical remission at week 14, HAQ-DI, duration of morning stiffness and health-related quality of life (QoL) by SF-36. The trial is ongoing, and the second phase is a blinded long-term extension period to evaluate the long-term safety, tolerability, and efficacy of the two once-daily doses (15 mg and 30 mg) of upadacitinib monotherapy in patients who have completed the first phase. More information on this trial can be found at www.clinicaltrials.gov (NCT02706951).

About SELECT-EARLY³

SELECT-EARLY is a Phase 3, multicentre, randomised, double-blind, parallel-group, active comparator controlled study designed to evaluate the safety and efficacy of upadacitinib monotherapy compared to methotrexate (MTX) monotherapy in adult patients with moderate to severe active rheumatoid arthritis who are MTX-naïve. In the first phase of the study, patients were randomized 1:1:1 to receive upadacitinib (15 mg or 30 mg, once-daily) or MTX. It includes a Japan sub-study in which subjects were randomised 2:1:1:1 to receive RINVOQ (7.5 mg, 15 mg or 30 mg, once-daily) or MTX.

The primary endpoints included the percentage of subjects achieving ACR50 response and clinical remission (based on DAS28-CRP) compared to MTX after 12 weeks and 24 weeks of treatment, respectively. Ranked secondary endpoints included the percentage of patients achieving ACR20 response, ACR70 response and low disease activity, as well as changes in the modified total Sharp score (mTSS) and the Health Assessment Questionnaire-Disability-Index (HAQ-DI). The trial is ongoing and includes a 48 week randomised, double-blind treatment period followed by a long-term extension period for up to an additional four years.

More information on this trial can be found at www.clinicaltrials.gov (NCT02706873).

About HUMIRA^® (adalimumab) in the European Union⁶

Adalimumab, in combination with methotrexate, is indicated for the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response to disease-modifying anti-rheumatic drugs, including methotrexate, has been inadequate.

For full adalimumab Summary of Product Characteristics visit:

https://www.medicines.org.uk/emc/product/7986/smpc

Adverse events should be reported. ▼ This medicinal product is subject to additional monitoring and it is therefore important to report any suspected adverse events related to this medicinal product. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Adverse events should also be reported to AbbVie on UK_PVVendor@abbvie.com

About AbbVie in Rheumatology

For more than 20 years, AbbVie has been dedicated to improving care for people living with rheumatic diseases. Our longstanding commitment to discovering and delivering transformative therapies is underscored by our pursuit of cutting-edge science that improves our understanding of promising new pathways and targets in order to help more people living with rheumatic diseases reach their treatment goals

References:

1. Fleischmann R, et al. Long-Term Safety and Effectiveness of Upadacitinib or Adalimumab in Patients with Rheumatoid Arthritis: Results at 72 weeks from the SELECT-COMPARE Study. 2020 EULAR E-Congress; THU0201
2. Smolen J, et al. Upadacitinib as Monotherapy in Patients with Rheumatoid Arthritis and Prior Inadequate Response to Methotrexate: Results at 84 Weeks From the SELECT-MONOTHERAPY Study. 2020 EULAR E-Congress; THU0213
3. Peterfy CG, et al. Radiographic Outcomes in Patients with Rheumatoid Arthritis Receiving Upadacitinib as Monotherapy or in Combination with Methotrexate: Results at 2 years from the SELECT-COMPARE and SELECT-EARLY Studies. 2020 EULAR E-Congress; THU0211
4. Cohen S, et al. Safety Profile of Upadacitinib Up to 3 Years of Exposure in Patients With Rheumatoid Arthritis. EULAR 2020; THU0197.
5. RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co. KG; March 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
6. HUMIRA [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co KG. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000481/WC500050870.pdf. Accessed May 18, 2020.