AbbVie has secured FDA Priority Review for its investigational JAK1-selective inhibitor upadacitinib for the treatment of moderate to severe rheumatoid arthritis (RA), marking a significant step in the company's strategy to diversify beyond its mega-blockbuster Humira.
The regulatory milestone comes at a critical time for AbbVie as Humira, the world's top-selling drug with expected peak sales of $21 billion, faces growing biosimilar competition in Europe and is set to lose patent protection in the US by 2023. The FDA decision on upadacitinib is anticipated in the third quarter of 2019.
Promising Clinical Performance
Clinical trial data suggests upadacitinib may be more effective at treating RA than Humira itself, positioning the oral medication as a potential cornerstone of AbbVie's future portfolio. Industry analysts project the drug could eventually generate annual sales exceeding $3 billion.
Beyond rheumatoid arthritis, AbbVie is conducting phase 3 trials of upadacitinib across multiple immune-mediated conditions, including atopic dermatitis, psoriatic arthritis, Crohn's disease, ulcerative colitis, and ankylosing spondylitis—indicating the company's ambitions for a broad label expansion strategy.
Humira's Declining Dominance
AbbVie's fourth-quarter financial results revealed the beginning of Humira's market erosion. While US sales increased approximately 9% year-over-year, international sales fell nearly 15%—representing a decline of almost $300 million—due to direct biosimilar competition in European and other international markets.
Overall, Humira's global revenue grew just 1% to $4.9 billion in the quarter, down from more than $5.1 billion in the previous three-month period. The company projects biosimilar impact on Humira's international sales to reach approximately $2 billion for the full year.
Comprehensive Portfolio Diversification
Upadacitinib represents just one element of AbbVie's broader diversification strategy. The company recently received FDA approval for Orilissa (elagolix), the first new endometriosis treatment in over a decade. Expected to be available in US pharmacies by early August, analysts at Evaluate Pharma have listed Orilissa among the top 10 potential launches of 2018, with projected 2022 sales of $1.21 billion.
Additionally, AbbVie's interleukin-23 inhibitor risankizumab for plaque psoriasis is under FDA review after demonstrating superiority over Johnson & Johnson's competing IL-23 drug Tremfya (guselkumab) in head-to-head trials. Market analysts estimate risankizumab could generate approximately $2.5 billion in annual sales.
The company is also focusing on growing established products in its oncology portfolio, particularly Imbruvica (ibrutinib) and Venclexta (venetoclax) for blood cancers, developed through partnerships with Janssen and Roche respectively.
Competitive Landscape for JAK Inhibitors
Upon approval, upadacitinib will enter a market with two established JAK inhibitor competitors—Eli Lilly's Olumiant and Pfizer's Xeljanz. Despite the growing excitement surrounding this therapeutic class, these oral treatments face a complex competitive landscape, especially with numerous low-cost biosimilars of injectable biologics entering the market.
However, the convenience of oral administration offered by JAK inhibitors may ultimately override cost considerations that would otherwise favor biosimilar adoption, particularly for patients seeking alternatives to injectable therapies.
Setbacks in Development Pipeline
AbbVie's diversification efforts have not been without challenges. Earlier this year, the company abandoned plans for accelerated review of rovalpituzumab tesirine (Rova-T) following disappointing phase 2 results in small cell lung cancer. Prior to these results, Rova-T had been forecast as a potential $5 billion blockbuster, and its setback triggered a significant drop in AbbVie's share price.
The European Medicines Agency is also reviewing upadacitinib for adult patients with moderate to severe rheumatoid arthritis, potentially expanding the drug's global reach as AbbVie works to establish its post-Humira commercial foundation.
