Upadacitinib Meets All Primary and Ranked Secondary Endpoints Including Superiority Versus Adalimumab in Phase 3 Study in Rheumatoid Arthritis

 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced positive top-line results from the Phase 3 SELECT-COMPARE clinical trial showing that after 12 weeks, upadacitinib (15 mg, once-daily) met the primary endpoints of ACR20^a and clinical remission^b versus placebo.¹ All ranked secondary endpoints were also achieved versus either placebo or adalimumab (40 mg every other week).¹ The ongoing study evaluates upadacitinib, an investigational oral JAK1-selective inhibitor, in patients with moderate to severe rheumatoid arthritis who are on a stable background of methotrexate and had an inadequate response.¹ Upadacitinib is not approved by regulatory authorities and its safety and efficacy have not been established.

"These results show a significant impact on both signs and symptoms and radiographic progression compared to placebo, as well as improvements in important measures such as ACR response and low disease activity compared to adalimumab," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "We are excited by these strong results which add to the body of evidence that support the potential of upadacitinib to be an important treatment option for patients with rheumatoid arthritis."

Rheumatoid arthritis, which affects an estimated 23.7 million people worldwide, is a chronic and debilitating disease.¹⁵ Despite the range of available treatments, many patients with rheumatoid arthritis still do not achieve clinical remission or low disease activity targets.^16-18

The study showed that at week 12, 71 percent of patients receiving an oral once-daily dose of upadacitinib 15 mg achieved an ACR20 response, compared with 36 percent of patients receiving placebo.¹ A significantly higher proportion of patients receiving upadacitinib achieved clinical remission (based on Disease Activity 28 [DAS28] C-Reactive Protein [CRP]) compared with placebo at week 12 (29 percent versus 6 percent, respectively).¹ Patients receiving upadacitinib achieved ACR50/70 responses of 45/25 percent compared to 15/5 percent of patients receiving placebo at week 12.¹ Additionally low disease activity (LDA) based on DAS28(CRP) was seen in 45 percent of patients receiving upadacitinib compared to 29 percent receiving adalimumab and 14 percent receiving placebo at week 12, respectively.¹

                  SELECT-COMPARE Efficacy Results at Week 12†
                  ------------------------------------------

                   Upadacitinib                          Adalimumab     Placebo
                                                                        (n=651)
                       15 mg                              40 mg EOW

                      (n=651)                              (n=327)
                      ------                               ------

    ACR20a            71%***#                                       63%         36%
    ------            -------                                       ---          ---

    ACR50a           45%***###                                      29%         15%
    ------           ---------                                      ---          ---

    ACR70a           25%***###                                      13%          5%
    ------           ---------                                      ---          ---

    Clinical
     Remission
     (DAS
     28-CRP)b        29%***###                                      18%          6%
    ----------       ---------                                      ---          ---

    Low
     Disease
     Activity
     (DAS28-CRP)c    45%***###                                      29%         14%
    -------------    ---------                                      ---          ---

    †Primary endpoints included ACR20
     and clinical remission based on
     DAS28(CRP) for upadacitinib versus
     placebo (superiority). Ranked
     secondary endpoints included ACR 50
     versus adalimumab (both non-
     inferiority and superiority) and
     LDA versus adalimumab (non-
     inferiority) and versus placebo
     (superiority). All other
     comparisons were not adjusted for
     multiplicity. Not all ranked
     secondary endpoints shown.

    a ACR20/50/70 is defined as
     American College of Rheumatology 20
     percent/50 percent/70 percent
     improvements in both tender and
     swollen joint counts, plus 3 of the
     following: patient assessments of
     pain, global disease activity and
     physical function, physician global
     assessment of disease activity and
     acute phase reactant (high
     sensitivity c-reactive protein).

    b Clinical remission was based on
     Disease Activity Score with 28
     joint counts (C-reactive protein)
     (DAS28 [CRP]) less than 2.6.

    c LDA was defined by a clinical
     response Disease Activity Score
     with 28 joint counts (C-reactive
     protein) (DAS28 [CRP]) less than or
     equal to 3.2.

    ***Denotes statistical significance
     at the 0.001 level for comparison
     versus placebo.

    #Denotes statistical significance at
     the 0.05 level for comparison
     versus adalimumab.

    ###Denotes statistical significance
     at the 0.001 level for comparison
     versus adalimumab.

Study findings also showed superiority of upadacitinib over adalimumab, on ranked secondary endpoints that compared both groups.¹ At week 12, 45 percent of upadacitinib patients achieved ACR50 compared with 29 percent of adalimumab patients.¹ Additionally, upadacitinib was superior to adalimumab in reduction of pain as measured by the Patient's Assessment of Pain (based on the Visual Analog Scale [VAS]), and improvements in physical function, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI), at week 12.¹

Following 26 weeks of treatment, upadacitinib (n=593) significantly inhibited radiographic progression as measured by the change in modified total Sharp score (mTSS) from baseline, compared to placebo (n=599) (0.24 versus 0.92, p<0.001).¹ The inhibition of joint damage is important for rheumatoid arthritis patients as this can lead to permanent loss of function and subsequent disability.¹⁹

In this study, the safety profile of upadacitinib was consistent with previously reported results.^1-6 No new safety signals were detected.¹ Through Week 26, serious adverse events occurred while on the original randomized treatment assignment in 3.7 percent of patients receiving upadacitinib, 4.3 percent of patients receiving adalimumab and 2.9 percent of patients on placebo.¹ Serious infections occurred in 1.8/1.5/0.8 percent of patients on upadacitinib/adalimumab/placebo groups, respectively. There were no deaths in the upadacitinib group, two deaths in the adalimumab group (0.6 percent) and two deaths in the placebo group (0.3 percent) through week 26.¹ No adjudicated major adverse cardiovascular events (MACE) were reported in the upadacitinib group through week 26.¹ There were two patients with MACE in the adalimumab group (0.6 percent) and three in the placebo group (0.5 percent) through week 26.¹ In terms of adjudicated venous thromboembolic events (VTE) through Week 26, one patient had a deep vein thrombosis (DVT; 0.15 percent) and another had a pulmonary embolism (PE; 0.15 percent) in the upadacitinib group, three patients had a PE in the adalimumab group (0.92 percent) and one had a PE in the placebo group (0.15 percent).¹ Across the SELECT rheumatoid arthritis program, including both the placebo-controlled and extension periods, the rate of DVT and PE remains consistent with the background rate for the rheumatoid arthritis patient population.^1-4,20-22

Additional results of SELECT-COMPARE, the fourth of six Phase 3 studies in the SELECT rheumatoid arthritis clinical trial program, will be presented at a future medical meeting and published in a peer-reviewed publication. AbbVie plans global regulatory submissions for upadacitinib in rheumatoid arthritis in the second half of 2018.

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