AbbVie’s Humira loss of exclusivity has been a missed opportunity for competitors

Humira first received FDA approval in 2002. Credit: Summit Art Creations / Shutterstock

AbbVie has maintained a strong position within the immunology space for the past few years, largely due to the success of its antitumour necrosis factor (TNF) agent, Humira (adalimumab).

On 31 December 2002, the drug received its first US Food and Drug Administration (FDA) approval to treat rheumatoid arthritis in adult patients and saw $246m in US sales the following year on the market.

In subsequent years, the strength of this asset has only grown with its expansion into additional diseases, with annual US sales peaking in 2022 at $18.6bn.

However, with the loss of patent protection in the US at the start of 2023 and the ensuing flood of adalimumab biosimilars to the market, AbbVie has faced a decline in sales of Humira, indicated by a 39.9% decrease in first-quarter year-over-year revenue from Humira in the US in 2024, which has been attributed to biosimilar competition.

This predicted scenario, once viewed as an opening for competitors to knock AbbVie off its throne, is now seen as a lost opportunity.

Aware of Humira’s inevitable loss of protection in the US, AbbVie positioned its next-generation therapies, the anti-interleukin (IL)-23 inhibitor biologic Skyrizi and the Janus kinase inhibitor (JAKi) Rinvoq (upadacitinib), as replacements.

AbbVie’s two-pronged approach towards Humira was a unique strategy, as other competitors typically focus on positioning a signal asset as the next-generation offering.

Upadacitinib as the second candidate was of note due to the general safety concerns associated with the JAKi drug class at the time.

With these two therapies, AbbVie followed Humira’s game plan of targeting multiple common diseases, such as inflammatory bowel disease (IBD) and psoriasis.

Throughout AbbVie’s retooling efforts, its stiffest challenges have been with the evolving IL-23 drug class, as the only JAKi of note in recent years has been Bristol Myers Squibb‘s Sotyktu, and though Sotyktu has been approved to treat psoriasis, trial failures in ulcerative colitis (UC) and Crohn’s disease have reduced the therapy’s potential as a blockbuster or challenger.

However, with the development of an IL-23-targeting agent, AbbVie has been directly challenged by competitor assets: Eli Lilly’s Omvoh and Janssen Biotech’s Tremfya.

Tremfya was the first of the three to reach the market, with approval for the treatment of plaque psoriasis in the US in July 2017 and in the EU in November 2017.

This was followed by Skyrizi’s April 2019 US approval, and more recently, Omvoh was approved to treat UC in May (EU) and October (US) 2023.

Once seen as a three-horse race, the IL-23 market is now led by AbbVie’s Skyrizi, driven by its four approved indications compared only to two for Tremfya.

The failure of Omvoh to show superiority over the older, anti-IL-23/12 therapy, Janssen’s Stelara, has only bolstered AbbVie’s standing.

In addition to navigating past the loss of Humira’s patent exclusivity and maintaining its place within the market, recent acquisitions indicate AbbVie’s intention to further strengthen its position within the immunology space.

On 13 June this year, AbbVie announced a license agreement with FutureGen to develop FG-M701, a TNF-like cytokine 1A (TL1A) inhibitor.

TL1A has garnered significant attention as a therapeutic target after the substantial acquisition prices paid for assets last year: $10.3bn by Merck, $7.1bn by Roche, and $1.5bn by Sanofi.

The upfront cost of $150m by AbbVie could be seen as measured in comparison.

AbbVie also announced on 27 June 2024 the acquisition of Celsius Therapeutics, including its CEL383 candidate, an anti-triggering receptor expressed on myeloid cells 1 antibody that has completed a Phase I clinical study for the treatment of IBD, for $250m.