INXN-2001

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.