Mirikizumab

AbbVie announced Tuesday that its IL-23 inhibitor Skyrizi (risankizumab) met all primary and secondary endpoints in a head-to-head trial against Johnson & Johnson's IL-12 and IL-23 antagonist Stelara (ustekinumab) in Crohn's disease. "We are encouraged by these results, which demonstrate the impact Skyrizi can have in helping patients achieve both clinical and endoscopic remission," commented Roopal Thakkar, chief medical officer at AbbVie.The Phase III SEQUENCE study recruited 527 patients with moderately-to-severely active Crohn's disease who failed one or more anti-TNF therapies. Participants randomised to Skyrizi received intravenous induction at weeks 0, 4 and 8, and a subcutaneous injection of the drug starting at week 12 and every 8 weeks thereafter. Those in the Stelara group were given an intravenous dose at week 0 and a subcutaneous injection every 8 weeks after that.Benefit on clinical, endoscopic remissionThe first primary endpoint of non-inferiority for clinical remission based on the Crohn's Disease Activity Index (CDAI) at week 24 was achieved with rates of 59% for Skyrizi versus 40% for Stelara. For the second primary endpoint of endoscopic remission at week 48, Skyrizi achieved superiority with a rate of 32% versus 16% for Johnson & Johnson's therapy.Meanwhile, secondary goals included the percentage of patients achieving clinical remission at week 48 based on the CDAI, with Skyrizi demonstrating superiority over Stelara. AbbVie noted that safety results were consistent with Skyrizi's overall safety profile, and no new risks were identified. Full results from the SEQUENCE study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal.Skyrizi is cleared in both the US and Europe for the treatment of moderately-to-severely active Crohn's disease. The drug, which AbbVie is partnered on with Boehringer Ingelheim, is also approved for patients with plaque psoriasis, active psoriatic arthritis, and recorded sales of $1.9 billion in the second quarter. Stelara is approved for multiple autoimmune indications as well, including Crohn's disease, and generated second-quarter sales of $2.8 billion. It is also on the list of 10 drugs recently selected for the first-ever Medicare price negotiations.Stelara challenged on two frontsAlong with Skyrizi, Stelara is facing challenges in head-to-head Crohn's disease studies against Eli Lilly's anti-IL-23p19 monoclonal antibody mirikizumab and Johnson & Johnson's own IL-23 blocker Tremfya (guselkumab), with top-line data from the latter two also due this year. Analysts at Morgan Stanley suggested that the SEQUENCE data "represents a catalyst to drive continued uptake [of Skyrizi] and has the potential to become a preferred front-line therapy."With a key US patent on Stelara set to expire in September, a number of biosimilar contenders are also lined up to enter the market later this year or in 2024. A FirstWord report last year suggested that payers may be resistant to Skyrizi once Stelara is exposed to biosimilar competition, and if AbbVie's drug comes at a substantial premium to those biosimilars. Although one European key opinion leader (KOL) predicted that if the SEQUENCE trial is positive for Skyrizi, it could wipe out the Crohn's market for both Stelara and its biosimilars. Should it turn out to be negative, the KOL said it should "provide a big push" for Stelara biosimilars.

Pictured: AbbVie corporate office/iStock, vzphotos With the U.S. launch of the first Humira (adalimumab) biosimilars in July, the Crohn’s disease market is poised for a “transformative” shift as AbbVie loses its iron grip on the patient population, according to a new report released Thursday from data and analytics company GlobalData. Over the next few years, GlobalData predicts another company will displace the pharma giant in the Crohn’s disease (CD) market, driven by advancements in biologics and oral small molecules. Second-quarter 2023 sales already revealed hastily slipping revenues for Humira—a 25% drop compared to the same period last year, bringing in $4 billion. Erosion for the year is projected at 35%. AbbVie is leaning heavily on Skyrizi, its anti-IL-23 drug, and Rinvoq, its oral JAK inhibitor for patients after anti-Tumor Necrosis Factor (TNF) treatment failure, to bolster sales amidst the decline. “With a focus on biologic-exposed CD patients, novel therapies for TNF-refractory individuals are gaining prominence,” GlobalData said. AbbVie has enjoyed its standing as market leader for Crohn’s with sales of $2.7 billion last year for the indication in the eight major markets, according to GlobalData. But that dominance is quickly eroding. “The recent launch of adalimumab biosimilars not only will cause an overall reduction in the cost of treatment, but also provide the opportunity for another company to knock AbbVie from its standing as the market leader within CD,” Adeleke Badejo, senior analyst of immunology at GlobalData, said in a statement. Humira’s competition had already been heating up with the approval of Janssen’s Stelara—an IL-23 and IL-12 blocker—with $2.1 billion in 2022 sales in the market. Takeda’s Entyvio binds to the α4β7 integrin to keep white blood cells from entering the gastrointestinal tract to reduce inflammation. It took $1.7 billion of Crohn’s sales in the major markets last year. However, as GlobalData points out, Stelara and Entyvio are viewed and prescribed as second- or third-line therapies following failure with Humira or other anti-TNF biologics. All three therapies now face decline with the approval and commercialization of biosimilars, some already entering the market and others coming soon. Badejo points out the strategy for most companies hoping to knock AbbVie off its pedestal appears to be targeting the market already exposed to biologic treatment for their disease, instead of attempting to create a next-generation replacement of Humira. In clinical trials, 36% of patients on Humira achieved and maintained remission after 56 weeks, a 4% drop from the number that had achieved and maintained remission at 26 weeks, leaving a large percentage of the Crohn’s population who don’t find long-lasting relief of symptoms on the biologic. “This strategy of developing therapies for the TNF-refractory patient group is a viable approach,” Badejo said, anticipating that competition within that population will heat up five to 10 years from now. Janssens’ Tremfya, currently approved for psoriasis and psoriatic arthritis, is hoping to push into the Crohn’s space. A Phase II trial showed that 73% of adults with severe Crohn’s disease achieved clinical remission when treated with the drug at its highest dose. Approval and launch of the treatment for this indication is anticipated in the next two to three years. Eli Lilly’s human monoclonal antibody Mirikizumab entered the Japanese market as the first IL-23p19 inhibitor for ulcerative colitis earlier this year. It’s currently in Phase III testing for Crohn’s. Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.