According to the Rheumatoid Arthritis Support Network, over 1.3 million Americans and as much as 1% of the worldwide population suffers from rheumatoid arthritis, one of the most common autoimmune disorders –- more common than psoriasis, Crohn’s disease, multiple sclerosis and lupus. Rheumatoid arthritis symptoms are triggered when a person’s antibodies attack the synovial joint fluid, causing chronic inflammation.
AbbVie (NYSE: ABBV) announced positive top-line results from its Phase 3 clinical trial of upadacitinib in patients with moderate to severe rheumatoid arthritis who are on a stable background of methotrexate and had an inadequate response. The results showed that upadacitinib met the primary endpoints of ACR20 response (see note a below) and clinical remission versus placebo. All ranked secondary endpoints were also achieved versus either placebo or adalimumab (Humira, 40 mg every other week).
John Carroll of Endpoints News writes that Geoffrey Porges, an analyst with Leerink, stated in his note to investors:
The total clinical experience of upadacitinib has now increased substantially without demonstrating a major risk for VTEs [venous thromboembolic events], which we believe reduces the risk of unexpected asset failure. After the recent failure of Rova-T in third-line small cell lung cancer, and the related drop in AbbVie’s stock value of >20%, the risk of a subsequent pipeline failure now also appears substantially reduced.
Mr. Carroll writes further that “AbbVie execs are promising peak sales in the range of $6.5 billion a year” for upadacitinib.
The study showed that at week 12, 71% of patients receiving an oral once-daily dose of upadacitinib 15 mg achieved an ACR20 response, compared with 36% of patients receiving placebo. 29% of patients receiving upadacitinib achieved clinical remission compared with 6% of placebo patients. ACR50 and ACR70 responses were 45% and 25%, respectively, compared with only 15% and 5% percent of placebo patients. Finally, low disease activity was seen in 45% of patients receiving upadacitinib compared to 29% receiving adalimumab and 14% receiving placebo.
† Primary endpoints included ACR20 and clinical remission based on DAS28-CRP — a disease activity score for rheumatoid arthritis — 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% / 50% / 70% 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).
*** 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.
Source: AbbVie
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. 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.
– Michael Severino, MD, executive vice president, research and development and chief scientific officer, AbbVie.
Upadacitinib is an investigational oral agent engineered to selectively inhibit the JAK1 signaling protein, which plays an important role in the pathophysiology of immune-mediated disorders. Phase 3 trials of upadacitinib in rheumatoid arthritis, psoriatic arthritis and Crohn’s disease are ongoing, and it is also being investigated to treat ulcerative colitis, ankylosing spondylitis, atopic dermatitis and giant cell arteritis.
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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