FDA Approves AbbVie's Humira (Adalimumab) for Moderately to Severely Active Ulcerative Colitis in Pediatric Patients Aged 5 and Older

Compiled by Keke

On February 24, AbbVie announced that the U.S. FDA approved Humira (adalimumab, brand name Humira) for the treatment of moderate to severe active ulcerative colitis (UC) in children aged 5 years and older.

AbbVie stated that this approval is based on the results of the pivotal Phase 3 clinical study, ENVISION I. The study demonstrated that Humira met the co-primary endpoint of clinical remission defined by the Partial Mayo Score (PMS) at Week 8, and among patients who responded at Week 8, it also met the co-primary endpoint of clinical remission defined by the Full Mayo Score (FMS) at one year (Week 52). Clinical remission was defined as a PMS or FMS of ≤2, with no individual subscore >1.

ENVISION I is a randomized, double-blind, multicenter Phase 3 study designed to evaluate the efficacy, safety, and pharmacokinetics of subcutaneously administered Humira in pediatric patients (aged 4–17 years) with moderately to severely active ulcerative colitis (UC), defined as a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of 6–12 and an endoscopic subscore of 2–3, as confirmed by central endoscopic review.

By Week 8, patients in both dose groups received Humira 2.4 mg/kg (maximum 160 mg) at Week 0, 1.2 mg/kg (maximum 80 mg) at Week 2, and 0.6 mg/kg (maximum 40 mg) at Weeks 4 and 6. The high-dose group also received an additional dose of 2.4 mg/kg (maximum 160 mg) at Week 1. Between Week 8 and Week 52, patients received double-blind placebo or Humira 0.6 mg/kg (maximum 40 mg) every other week or weekly. The co-primary endpoints of the study were the clinical remission rate based on the partial Mayo score at Week 8 (defined as a partial Mayo score ≤2 with no individual subscore >1) and the clinical remission rate based on the Mayo score at Week 52 (defined as a Mayo score ≤2 with no individual subscore >1).

The study results showed that at the end of the 8-week induction period, 60% (28/47) of patients receiving high-dose Humira achieved clinical remission during each premenstrual syndrome (PMS) episode, compared to 43% (13/30) of patients receiving low-dose Humira. At Week 52, among those who had responded to PMS treatment by Week 8, 45% of patients in the high-dose Humira group achieved remission during each fibromyalgia syndrome (FMS) episode, compared to 29% in the low-dose Humira group and 33% in the placebo group. Due to the small sample size, the interpretability of the placebo data was limited.

The approved dosage of Humira will be determined based on the child's weight, as follows:

For patients aged 18 years and older, as well as those whose Humira treatment regimen is well-controlled, it is recommended to continue using the recommended pediatric dose.

In the ENVISION I study, no new safety signals for Humira were observed. During any period of Humira exposure in this study, 22.6% of patients experienced serious adverse events. The most frequently reported treatment-emergent adverse events (≥5%) during the induction and maintenance phases were headache and worsening of ulcerative colitis. No deaths, malignancies, active tuberculosis, or demyelinating diseases were observed in this study.

In 2018, Humira was the world’s best-selling prescription drug, a trend that persisted for several years. The drug generated approximately $20 billion in revenue for AbbVie in 2018 alone. Although biosimilars were unable to enter the U.S. market before 2023 due to patent protection, biosimilar competitors emerged in Europe in late 2018. Companies including Novartis, Amgen, Mylan, and Samsung Bioepis developed biosimilars of Humira, leading to a sharp decline in its global sales.

In December 2021, AbbVie announced positive results from the U-ACHIEVE Phase 3 induction study of Rinvoq (upadacitinib), another medication for moderate-to-severe ulcerative colitis (UC). The trial met its primary endpoint of clinical remission in adult patients at 8 weeks. Another Phase 3 induction study, U-ACCOMPLISH, also confirmed that Rinvoq improved clinical, endoscopic, and histological outcomes in patients with UC.

Reference Sources:

1.Humira Bags Another FDA Approval, This Time for Pediatric Ulcerative Colitis

2.HUMIRA® (adalimumab) Receives FDA Approval to Treat Pediatric Patients Living with Moderately to Severely Active Ulcerative Colitis