Johnson & Johnson Highlights Stelara's Safety Advantage Over Humira in Crohn's Disease Despite Comparable Efficacy

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Johnson & Johnson's immunology blockbuster Stelara and AbbVie's flagship product Humira are going head-to-head in Crohn's disease (CD). Although efficacy did not meet J&J's expectations, company executives noted that Stelara's safety profile is superior to that of TNFα inhibitors like Humira, which will help the drug maintain its competitive advantage in the market.

According to data recently presented at Digestive Disease Week (DDW) in the United States, in the head-to-head Phase 3 SEAVUE study, although Stelara demonstrated efficacy comparable to Humira, it did not surpass Humira across any endpoints. At week 52, 64.9% of patients in the Stelara treatment group achieved clinical remission, compared with 61% in the Humira treatment group, but the difference was not statistically significant.

Following in-depth data analysis, Stelara demonstrated a numerical advantage across secondary endpoints, although none reached statistical significance. Approximately 61% of patients in the Stelara group achieved corticosteroid-free remission, compared with 57.4% in the Humira group. Furthermore, the proportion of patients achieving clinical response was 6% higher in the Stelara group than in the Humira group, while the rate of patient-reported symptom resolution was approximately 1% higher. Conversely, the proportion of patients achieving clinical remission at Week 16 was approximately 3% higher in the Humira group, which also demonstrated a slight advantage over Stelara in facilitating endoscopic remission among certain patients.

Given that patients with Crohn’s disease require treatment for an average of 60 years, long-term tolerability is critically important. Specifically, in the SEAVUE study, 6.3% of patients in the Stelara treatment arm discontinued therapy due to adverse events, compared with 11.3% in the Humira treatment arm.

In the coming years, this safety advantage may benefit Stelara, as the drug will face intense competition from Humira, Humira biosimilars, and next-generation Crohn's disease therapies. Humira biosimilars have already entered the European market and will begin launching in the United States starting in 2023.

However, as Jan Wehkamp pointed out, this choice may not ultimately lie with patients; payers tend to favor lower-cost medications, and it remains unclear what discounts pharmaceutical manufacturers will offer for Humira biosimilars.

However, facing brand competition, Johnson & Johnson has already begun to lower prices. A report sent to clients last autumn by analysts at Wall Street investment bank Bernstein pointed out that, due to the launch of AbbVie’s next-generation psoriasis and rheumatoid arthritis drugs Skyrizi and Rinvoq, the “implied price” of Johnson & Johnson’s Stelara fell by 19% in the third quarter of 2020 compared to the same period in 2019, while sales during the same period grew by 14.7%, reaching $1.95 billion.

Regarding other emerging contenders for Crohn's disease treatment, a new wave of IL-23 inhibitors is emerging, including AbbVie's Skyrizi, Eli Lilly's mirikizumab, AstraZeneca's brazikumab, and Johnson & Johnson's own Tremfya, the latter of which has already received regulatory approval for plaque psoriasis and psoriatic arthritis.

Jan Wehkamp, Regional Vice President of Gastroenterology at Janssen, a Johnson & Johnson company, noted that in the field of Crohn's disease, several JAK inhibitors are also under development, such as AbbVie's Rinvoq and Gilead's Jyseleca, but this class of drugs carries serious black box warnings.

Pfizer's JAK inhibitor Xeljanz has been approved for the treatment of ulcerative colitis; however, in July 2019, a boxed warning was added to its label indicating that a 10 mg twice-daily dosage increases the risk of thrombosis and potential death. Currently, the drug is only approved for patients who have had an inadequate response to or are intolerant of other therapies. AbbVie's JAK inhibitor Rinvoq is also seeking to gain a foothold in the gastrointestinal market, but the FDA warned last year that the drug increases the risk of serious infections, malignancies, and thrombosis when used to treat rheumatoid arthritis.

However, Jan Wehkamp noted that the data from the head-to-head SEAVUE study represent only part of the puzzle. A recent real-world study comparing Stelara and Humira in Crohn’s disease demonstrated that among patients previously treated with TNF inhibitors, Stelara exhibited superior efficacy to Humira.

Jan Wehkamp noted that while these trials cannot be directly compared, they do provide valuable context for the real-world management of Crohn's disease. Given that many patients have already received prior therapies, if they have been treated with anti-TNF agents and subsequently lost response, a drug with a novel mechanism of action or from a new therapeutic class is more likely to succeed."

At the end of 2019, Stelara received approval for the treatment of ulcerative colitis, expanding its foothold in the gastrointestinal disease field. In 2020, Stelara's sales grew by nearly 20%, reaching $7.94 billion.

Source: Johnson & Johnson spotlights safety edge after Stelara's near miss against Humira in Crohn's